#tnfa

[exeggcute]

there's a lot of data floating around about antidepressants (specifically tricyclics and SSRIs) as a decently effective form of treatment for certain gastrointestinal symptoms, and part of me has always been a little resistant to the idea because it risks coming across as an "actually it was all in your head" thing—and tbh frequently does come across that way lol)—but if you cut through the vague air of dismissiveness or whatever there's still good reason to believe it's legit since (1) we're pretty confident the ~gut-brain axis~ exists even if we're not sure exactly how or why and (2) anything that affects the brain is bound to affect the rest of the body since, like, the brain is what's piloting the whole machine. there's a reason anti-emetics like zofran target the brain directly and not your stomach. and literally anyone with GI problems can tell you that worrying about those problems is almost guaranteed to make them worse.

BUT, APPARENTLY, wellbutrin (an SNRI) takes that shit to the next level by directly reducing TNFa levels in your gut. or allegedly does anyway, at least a little bit. and for the uninitiated, TNFa is an inflammatory protein that does useful stuff in your body but can get a little carried away with it sometimes (i.e., if you have an autoimmune disease); it's not the only culprit for intestinal inflammation, but it's one of the most common ones, so some of the most common drugs used to treat crohn's and colitis are "TNF inhibitors" like remicade and humira and enbrel. except where all of those are highly specialized artificial antibodies or genetically engineered shit that has to be grown painstakingly in a lab, wellbutrin is just a random pill. and obviously its effect on TNFa won't be as strong as an intravenous medication, and it's not the only random pill to affect TNF levels (apparently thalidomide also does lol) but I'm still like what the fuck that's crazy. and also wondering if I would've developed crohn's symptoms earlier if I hadn't been on wellbutrin in my teens and early 20s...

[moleculardepot]

Recombinant Canine TNF-alpha

Recombinant Canine TNF-alpha Catalog number: B2017868 Lot number: Batch Dependent Expiration Date: Batch dependent Amount: 1 μg Molecular Weight or Concentration: ~17.3 kDa Supplied as: Powder Applications: a molecular tool for various biochemical applications Storage: -20°C Keywords: TNFA, cTNF, cachectin, tumor necrosis factor ligand superfamily member 2 Grade: Biotechnology grade. All products…

[rnomics]

Nutrients, Vol. 16, Pages 1929: Gut Dysbiosis Shaped by Cocoa Butter-Based Sucrose-Free HFD Leads to Steatohepatitis, and Insulin Resistance in Mice

Background: High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and fish oil are considered to be a part of healthy diets. However, their differential effects on gut microbiome perturbations in mice fed high concentrations of these fats, in the absence of sucrose, remains to be elucidated. The aim of the study was to test whether the sucrose-free cocoa butter-based high-fat diet (C-HFD) feeding in mice leads to gut dysbiosis that associates with a pathologic phenotype marked by hepatic steatosis, low-grade inflammation, perturbed glucose homeostasis, and insulin resistance, compared with control mice fed the fish oil based high-fat diet (F-HFD). Results: C57BL/6 mice (5–6 mice/group) were fed two types of high fat diets (C-HFD and F-HFD) for 24 weeks. No significant difference was found in the liver weight or total body weight between the two groups. The 16S #rRNA sequencing of gut bacterial samples displayed gut dysbiosis in C-HFD group, with differentially-altered microbial diversity or relative abundances. Bacteroidetes, Firmicutes, and Proteobacteria were highly abundant in C-HFD group, while the Verrucomicrobia, Saccharibacteria (TM7), Actinobacteria, and Tenericutes were more abundant in F-HFD group. Other taxa in C-HFD group included the Bacteroides, Odoribacter, Sutterella, Firmicutes bacterium (AF12), Anaeroplasma, Roseburia, and Parabacteroides distasonis. An increased Firmicutes/Bacteroidetes (F/B) ratio in C-HFD group, compared with F-HFD group, indicated the gut dysbiosis. These gut bacterial changes in C-HFD group had predicted associations with fatty liver disease and with lipogenic, inflammatory, glucose metabolic, and insulin signaling pathways. Consistent with its microbiome shift, the C-HFD group showed hepatic inflammation and steatosis, high fasting blood glucose, insulin resistance, increased hepatic de novo lipogenesis (Acetyl CoA carboxylases 1 (Acaca), Fatty acid synthase (Fasn), Stearoyl-CoA desaturase-1 (Scd1), Elongation of long-chain fatty acids family member 6 (Elovl6), Peroxisome proliferator-activated receptor-gamma (Pparg) and cholesterol synthesis (β-(hydroxy β-methylglutaryl-CoA reductase (Hmgcr). Non-significant differences were observed regarding fatty acid uptake (Cluster of differentiation 36 (CD36), Fatty acid binding protein-1 (Fabp1) and efflux (ATP-binding cassette G1 (Abcg1), Microsomal TG transfer protein (Mttp) in C-HFD group, compared with F-HFD group. The C-HFD group also displayed increased gene expression of inflammatory markers including Tumor necrosis factor alpha (Tnfa), C-C motif chemokine ligand 2 (Ccl2), and Interleukin-12 (Il12), as well as a tendency for liver fibrosis. Conclusion: These findings suggest that the sucrose-free C-HFD feeding in mice induces gut dysbiosis which associates with liver inflammation, steatosis, glucose intolerance and insulin resistance. https://www.mdpi.com/2072-6643/16/12/1929?utm_source=dlvr.it&utm_medium=tumblr

[janeblr]

I’m getting my crp drawn on Friday and I’m holding my NSAIDs so it doesn’t skew the results but. Now I can’t sleep. I’m going to be in fucking agony the next few days. Just confirming my self diagnosis of seronegative axial spondylarthritis because I meet literally all the clinical features and have imaging to back it up(haha back). But no doctor has ever diagnosed me with anything besides “back hurty discs fucked” and regular osteoarthritis which, ouch, I’m 24(and was diagnosed at 19 😬😬😬). Idk I know it doesn’t matter because the treatment is NSAIDS which I take in kidney frying levels or TNFa antagonists, and I really don’t want to knock out my immune system when I work around sick people all the time. Augh I wish I could just cut open my back, scrub my spine with a scotch Brite pad, and snap everything back into place. Hell on earth

[biomedres]

Anti-TNFa –Induced Demyelination in a Patient with Rheumatoid Arthritis

Anti-TNFa –Induced Demyelination in a Patient with Rheumatoid Arthritis Biomedical Journal of Scientific & Technical Research

https://biomedres.us/fulltexts/BJSTR.MS.ID.005811.php

Tumor necrosis factor (TNF) alpha is an immunomodulatory cytokine, implicated in mechanism of inflammatory and autoimmunologic diseases, like multiple sclerosis (MS), rheumatoid arthritis (RA) and Crohn disease [1]. At present five anti-TNF agents are in clinical use including soluble TNFR2 (etanercept) and four anti-TNF specific monoclonal antibodies [2]. Etanercept has been shown to interfere with TNF bioavailability and it is approved for treatment of rheumatoid arthritis, juvenile rheumatoid arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. Treatment with etanercept and other anti-TNF therapeutics was associated with increased risks for bacterial, viral and fungal infections, hemocytopenias, congestive heart failure and development of T-cell lymphomas. In addition it was observed that RA patients treated with anti-TNF therapy are at risk either to develop or exacerbate demyelination within CNS [3]. Here we report a case of a first demyelinating episode in RA patient during etanercept therapy and discuss the possible association between TNF inhibition and clinical demyelination.

For more articles in Journals on Biomedical Sciences click here

bjstr

Follow on Twitter : https://twitter.com/Biomedres01 Follow on Blogger :https://biomedres01.blogspot.com/ Like Our Pins On : https://www.pinterest.com/biomedres/

[researchfindings]

Cytokines and systemic lupus erythematosus

SLE is an autoimmune rheumatic disease that principally affects women in the childbearing years.1 The prevalence of SLE varies between ethnic groups, being approximately 1:250 among black women, 1:1000 in Chinese women and 1:4300 in white women. SLE affects the joints, skin and blood in over 80% of patients and the kidneys, central nervous system and cardiopulmonary system in 30%–50% of patients. Between 10% and 30% of patients have anticardiolipin antibodies that are associated with arterial and venous thrombosis. The majority of patients demonstrate systemic manifestations, which may include fatigue, malaise, fever, anorexia, nausea and weight loss.

Many cytokines have been implicated in regulating disease activity and in the involvement of different organs in patients with SLE. This article reviews both the role of individual cytokines and discusses possible mechanisms of cytokine action in individual organs.

[tnfalphaelisa8]

Home

What Is Meant By TNF Alpha Elisa Kit Antibody?

The TNF alpha is a multifunctional proinflammatory cytokine, which belongs to the super family of tumor necrosis factor (TNF). The main functions of TNF alpha Elisa kit antibody are including its prime function in an immune response to the viral, bacterial, parasitic along with certain fungal infections as well as additionally its role in a necrosis of the particular tumors. The TNF alpha ELISA is an immune assay kit for the quantitative measurement of tumor necrosis factor alpha (TNFA) in the plasma, lysate samples and human serum and cell culture supernatants.Click here for more info https://www.bosterbio.com/

Exactly How Does TNF Elisa Works?

The quantikine human TNF alpha immune assay is a 3.5 to 4.5 hr solid phase Elisa made to determine the human TNF alpha in serum, cell culture supernates and plasma and so forth. It really includes E coli-delivered recombinant human TNF alpha in addition to antibodies increased against this protein. It has actually also been shown to completely quantitate the recombinant factor. According to the research, it has been shown that every immune assay can represent its drawbacks as well as benefits, only a few assays are appropriate for the measurement of TNF alpha in the clinical laboratories as well as exhibit that so far away the extent of TNF alpha in the human blood is still not yet synchronized.

The human TNF alpha Elisa kit is a solitary wash ninety min sandwich Elisa that specially made for the quantitative quantity of TNF alpha protein in the plasma, human serum and culture media. It additionally uses an exclusive simple step Elisa technology and quantitates the human TNF alpha with 4.32 pg/ml compassion. The Elisa technology really employs capture the antibodies that are conjugated to an affinity age, which is identified by the monoclonal antibody utilized to coat the basic step Elisa plates. This technique to sandwich Elisa allows the creation of antibody analyte sandwich difficult in one step and significantly minimizing the assay time.

Major Benefits Of Elisa Technology

The major advantages of basic action Elisa technology are consisting of:

- Entirely validated in biological samples

- Single wash protocol reduces assay time to 90 minutes or less

- 96 wells plate breakable into 12x8 wells strips

- High specificity, sensitivity and also reproducibility from the leading antibodies

Test Concept Of TNF Alpha Elisa Kit

The Elisa kit really utilizes a sandwich Elisa concept. This Micro Elisa plate offered in this kit has been pre-coated with an antibody certain to human TNF alpha. Its samples or standards are consisted of tomicro Elisa plate wells as well as additionally blended with the particular antibody. The TNF alpha Elisa kit is majorly triggered by the endotoxins, viral infections, lipopolysaccharides or any other bacterial parts by DNA damage, tissue injury as well as also by TNF alpha as well as IL-1, PDGF. It is generally expressed in neutrophils, macrophages, endothelial cells, NK-cells, mast cells, monocytes and activated lymphocytes. It additionally encourages the systematic or local inflammation along with urges the severe stage response. The dysregulation of TNF alpha is included in several diseases. To know more regarding this Elisa kit, you can click here to find out more.

[biomedicool]

Alcoholic Liver Disease

Pathogenesis 

Stage One

Ethanol is metabolised in the liver to acetaldehyde by alcohol dehydrogenase

which is in turn metabolised to acetate by aldehyde dehydrogenase.

As acetaldehyde is formed, NAD is metabolised to NADH as a cofactor in this reaction. 

This NADH inhibits the actions of isocitrate dehydrogenase and alpha ketoglutarate and fatty acid oxidation, meaning it favours fatty acid synthesis.

Fat builds up in vacuoles of hepatocytes and mitochondria begin to dysfunction under oxidative stress, creating reactive oxygen species. 

This fatty stage is known as steatosis and is stage one of alcoholic liver disease. It is reversible.

Stage Two

Inflammatory cytokines such as IL-6 and TNFa influx in, causing inflammation. 

Water begins to accumulate inside hepatocytes and they begin to balloon. This causes significant cholestasis.

The inflammatory cytokines stimulate hepatocytes to produce collagen, which can begin to form fibrosis. 

This collagen can be pericellular or around central veins, forming collagen bridges. This is a precursor for cirrhosis.

Stage Three

As the fibrosis progresses, hepatocytes begin to die and cirrhosis occurs. 

This is end-stage alcoholic liver disease and can lead to liver failure and death.

Liver function tests

In stage 1; all LFTs will be raised. AST and ALT will be raised by approximately 5-10x the upper reference limit except albumin. They will both usually be below 300IU/L. AST will be raised above ALT; this is different to other hepatic conditions such as cholestasis, tumours, hepatitis, where ALT will be above AST.

In stage 2; ALP and bilirubin will increase significantly as cholestasis occurs and blocks bile duct. This will usually be above 300IU/L, which is different from filtrative diseases, where ALP is usually raised to 200-250IU/L. AST and ALT may increase further.

In stage 3; AST and ALT are between 10-100x the upper reference limit, suggesting significant cirrhosis and damage to cells. AST will remain above ALT. GGT will be raised significantly, which is common with alcoholic liver disease. Albumin will be decreased, suggestive of total liver failure. In other hepatic conditions, liver damage usually does not reach this stage and so albumin stays within the range.

[siglerprescriptiondrugcards]

Infliximab

Common Brand Names: Remicade

Therapeutic Class: Monoclonal antibody, TNFa-blocking agent

Common Injectable Dosage Forms:

Lyophilized Powder for Injection: 100 mg/vial. Store under refrigeration at 2°C-8°C

Dosage Ranges:

In combination with methotrexate, to reduce the signs and symptoms, inhibit the progression of structural damage, and improve physical function in patients with moderately to severely active rheumatoid arthritis: 3 mg/kg given as an intravenous infusion followed by additional doses at 2 and 6 weeks then every 8 weeks thereafter. Doses may be increased up to 10 mg/kg or given every 4 weeks.

To reduce the signs and symptoms and to induce and maintain clinical remission in patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy AND to reduce the number of draining enterocutaneous and rectovaginal fistulas and to maintain fistula closure in patients with fistulizing Crohn’s disease: 5 mg/kg given as an intravenous infusion followed by additional doses at 2 and 6 weeks then 8 weeks thereafter. Doses may be increased up to 10 mg/kg. Patients who fail to respond within 14 weeks should discontinue therapy.

Administration and Stability: Infliximab may be used within 3 hours of reconstitution. Use 10 mL of Sterile Water for Injection, USP to dissolve the lyophilized powder. Vials should be gently swirled but not shaken. Allow the reconstitution to stand for 5 minutes. Further dilute to a total volume of 250 mL with 0.9% Sodium Chloride Injection, USP and with a final concentration of 0.4 mg/mL. The infusion should be administered over a period of not less than 2 hours using an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size of 1.2 µm or less).

Pharmacology/Pharmacokinetics: Infliximab competitively blocks the binding of human tumor necrosis factor alpha (TNFa) to its receptors. Infliximab does not neutralize TNFb (lymphotoxin a), a related cytokine that utilizes the same receptors as TNFa. Elevated concentrations of TNFa have been found in the joints of rheumatoid arthritis patients and in the stools of Crohn’s disease patients. The biological activities of TNFa include induction of pro-inflammatory cytokines such as interleukins (IL) 1 and 6, enhancement of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, induction of acute phase reactants and other liver proteins, as well as tissue degrading enzymes produced by synoviocytes and/or chondrocytes. The terminal half-life of infliximab is around 9 days.

Drug and Lab Interactions: Concurrent administration of etanercept (another TNFa-blocking agent) and anakinra (an interleukin-1 antagonist) has been associated with an increased risk of serious infection. TNFa-blocking agents, including infliximab, may result in similar toxicities when used with anakinra.

Contraindications/Precautions: Contraindicated in patients with known hypersensitivity to any murine proteins or other components of this product. Doses of over 5 mg/kg are contraindicated in patients with moderate-to-severe heart failure. Serious infections, some fatal, have occurred in patients receiving TNF-blocking agents. Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test. Do not use in patients with a clinically important, active infection. Use with caution in patients with a chronic infection or a history of recurrent infection. Discontinue use if a patient develops a serious infection. Use with caution in patients who have resided in regions where histoplasmosis or coccidioidomycosis is endemic. Cases of leukopenia, thrombocytopenia, and pancytopenia, some with fatal outcome, have been reported in patients receiving infliximab. Patients should seek immediate medical attention if they develop signs and symptoms of blood dyscrasias (e.g., persistent fever) while on infliximab. Use with caution in patients with preexisting central nervous system demyelinating or seizure disorders. Do not give live vaccines to patients using infliximab. No recommended in nursing mothers. Pregnancy Category B.

Monitoring Parameters: Vital signs, LFTs, s/s of infection, annual PPD

Adverse Effects: Acute infusion reactions, including fever, chills, chest pain, hypotension, dyspnea, hypertension, pruritus, and urticaria may occur with use. Infliximab increases the risk of developing infections, most commonly respiratory and urinary tract infections. Rare cases of lupus-like syndrome may occur. Less severe adverse effects include abdominal pain, dyspepsia, coughing, bronchitis, rhinitis, rash, pruritus, and headache. Crohn’s disease patients who were retreated with infliximab after a 2–4-year absence had a higher incidence of myalgia, arthralgia, pruritus, facial, hand, or lip edema, dysphagia, urticaria, sore throat, and headache.

Common Clinical Applications: Infliximab is used in treatment of rheumatoid arthritis, Crohn’s disease, ankylosing spondylitis, and treatment of and maintenance of ulcerative colitis that has not responded to conventional therapy.

[moleculardepot]

TNF-α Chimeric Mouse-Mouse Monoclonal Antibody

TNF-α Chimeric Mouse-Mouse Monoclonal Antibody Catalog number: B2017725 Lot number: Batch Dependent Expiration Date: Batch dependent Amount: 100 µg Molecular Weight or Concentration: N/A Supplied as: SOLUTION Applications: a molecular tool for various biochemical applications Storage: -20°C Keywords: DIF, Differentiation-inducing Factor, TNFA, TNFSF2, Tumor Necrosis Factor-α Grade: Biotechnology…

[wal-phisics]

subleq.fth

only forth definitions hex

system +order

variable meta.1

variable target.1

variable assembler.1

variable target.only.1

meta.1 +order definitions

  2 constant =cell

4000 constant size

8000 constant =end

 40 constant =stksz

100 constant =buf

0008 constant =bksp

000A constant =lf

000D constant =cr

007F constant =del

create tflash size cells here over erase allot

variable tdp

variable tep

variable tlast

size =cell - tep !

0 tlast !

: :m meta.1 +order definitions : ;

: ;m postpone ; ; immediate

:m there tdp @ ;m

:m tc! tflash + c! ;m

:m tc@ tflash + c@ ;m

:m t! over $FF and over tc! swap 8 rshift swap 1+ tc! ;m

:m t@ dup tc@ swap 1+ tc@ 8 lshift or ;m

:m taligned dup 1 and + ;m

:m talign there 1 and tdp +! ;m

:m tc, there tc! 1 tdp +! ;m

:m t, there t! 2 tdp +! ;m

:m $literal

 talign [char] " word count dup tc, for aft count tc, then next drop talign ;m

:m tallot tdp +! ;m

:m parse-word bl word ?nul count ;m

:m thead

 talign

 there tlast @ t, tlast !

 parse-word talign dup tc, for aft count tc, then next drop talign ;m

:m #dec dup >r abs 0 <# $A hold #s r> sign #> type ;m  ( n -- print number )

:m mdump aligned begin ?dup while swap dup @ #dec cell+ swap cell - repeat drop ;m

:m save-target parse-word drop decimal tflash there mdump ;m

:m .end only forth definitions decimal ;m

:m setlast tlast ! ;m

:m atlast tlast @ ;m

:m tvar

 get-current >r meta.1 set-current create r> set-current there , t, does> @ ;m

:m label:

 get-current >r meta.1 set-current create r> set-current there ,    does> @ ;m

:m tdown =cell negate and ;m

:m tnfa =cell + ;m ( pwd -- nfa : move to name field address )

:m tcfa tnfa dup c@ $1F and + =cell + tdown ;m ( pwd -- cfa )

:m compile-only tlast @ tnfa t@ $20 or tlast @ tnfa t! ;m ( -- )

:m immediate    tlast @ tnfa t@ $40 or tlast @ tnfa t! ;m ( -- )

:m half dup 1 and abort" unaligned" 2/ ;m

:m double 2* ;m

:m (') bl word find ?found cfa ;m

:m t' (') >body @ ;m

:m to' target.only.1 +order (') >body @ target.only.1 -order ;m

:m tcksum taligned dup $C0DE - $FFFF and >r

  begin ?dup while swap dup t@ r> + $FFFF and >r =cell + swap =cell - repeat

  drop r> ;m

:m mkck dup there swap - tcksum ;m

system -order

\ ---------------------------------- Forth VM --------------------------------

:m Z 0 t, ;m \ Address 0 must contain 0

:m NADDR there 2/ 1+ t, ;m

:m HALT 0 t, 0 t, -1 t, ;m

:m JMP 2/ Z Z t, ;m

:m ADD swap 2/ t, Z NADDR Z 2/ t, NADDR Z Z NADDR ;m

:m SUB swap 2/ t, 2/ t, NADDR ;m

:m NOP Z Z NADDR ;m

:m ZERO dup 2/ t, 2/ t, NADDR ;m

:m PUT 2/ t, -1 t, NADDR ;m

:m MOV 2/ >r r@ dup t, t, NADDR 2/ t, Z  NADDR r> Z  t, NADDR Z Z NADDR ;m

:m iLOAD there 2/ 3 4 * 3 + + 2* MOV 0 swap MOV ;m

:m iJMP there 2/ E + 2* MOV NOP ;m

:m iSTORE ( addr w -- )

  swap >r there 2/ 24 + 2dup 2* MOV 2dup 1+ 2* MOV 7 + 2* MOV r> 0 MOV ;m

assembler.1 +order definitions

: begin talign there ;

: again JMP ;

: mark there 0 t, ;

: if ( NB. "if" does not work for 8000 )

  2/ dup t, Z there 2/ 4 + dup t, Z Z 6 + t, Z Z NADDR Z t, mark ;

: until 2/ dup t, Z there 2/ 4 + dup t, Z Z 6 + t, Z Z NADDR Z t, 2/ t, ;

: +if   Z 2/ t, mark ;

: -if 2/ t, Z there 2/ 4 + t, Z Z there 2/ 4 + t, Z Z mark ;

: then begin 2/ swap t! ;

: while if swap ;

: repeat JMP then ;

assembler.1 -order

meta.1 +order definitions

 0 t, 0 t,        \ both locations must be zero

label: entry       \ used to set entry point in next cell

 -1 t,            \ system entry point

 B tvar {options}  \ bit #1=echo off, #2 = checksum on, #4=info, #8=die on EOF

 0 tvar h         \ dictionary pointer

 0 tvar primitive \ any address lower than this one must be a primitive

 0 tvar check     \ used for system checksum

 8000 tvar hbit   \ must contain 8000

 -2   tvar ntwo   \ must contain -2

 -1 tvar neg1     \ must contain -1

 1 tvar one       \ must contain  1

 2 tvar two       \ must contain  1

$10 tvar bwidth   \ must contain 16

 0 tvar INVREG    \ temporary register used for inversion only

 0 tvar {cold}    \ entry point of virtual machine program, set later on

 0 tvar {key}     \ execution vector for key?

 0 tvar {emit}    \ execution vector for emit

 0 tvar {literal} \ execution vector for literal

 0 tvar {ok}      \ execution vector for .ok

 0 tvar {echo}    \ execution vector for echo

 0 tvar ip        \ instruction pointer

 0 tvar w         \ working pointer

 0 tvar x         \ working pointer

 0 tvar t         \ temporary register for Virtual Machine

 0 tvar bl1       \ bitwise extra register

 0 tvar bl2       \ bitwise extra register

 0 tvar bt        \ bitwise extra register

 0 tvar tos       \ top of stack

 0 tvar {state}   \ compiler state

 0 tvar {hld}     \ hold space pointer

 $A tvar {base}   \ input/output radix

 -1 tvar {dpl}    \ number of places after fraction

 0 tvar {in}      \ position in query string

 0 tvar {handler} \ throw/catch handler

 0 tvar {last}    \ last defined word

 0 tvar #tib      \ terminal input buffer

 0 tvar {context} $E tallot \ vocabulary context

 0 tvar {current} \ vocabulary which new definitions are added to

 0 tvar {forth-wordlist} \ forth word list (main vocabulary)

 0 tvar {root-voc} \ absolute minimum vocabulary

 0 tvar {system}  \ system functions vocabulary

 =end                       dup tvar {sp0} tvar {sp} \ grows downwards

 =end =stksz 4 * -          dup tvar {rp0} tvar {rp} \ grows upwards

 =end =stksz 4 * - =buf - constant TERMBUF \ pad buffer space

 TERMBUF =buf + constant =tbufend

:m INC 2/ neg1 2/ t, t, NADDR ;m ( b -- )

:m DEC 2/ one  2/ t, t, NADDR ;m ( b -- )

:m INV ( b -- : invert NB. b - a = b + ~a + 1 )

 INVREG ZERO dup INVREG SUB dup INVREG swap MOV DEC ;m

:m ++sp {sp} DEC ;m

:m --sp {sp} INC ;m

:m --rp {rp} DEC ;m

:m ++rp {rp} INC ;m

:m a-optim >r there =cell - r> 2/ t! ;m

assembler.1 +order

label: start

 start 2/ entry t!

 {sp0} {sp} MOV

 {rp0} {rp} MOV

 {cold} ip MOV

 ( fall-through )

label: vm ( Forth Inner Interpreter )

 ip w MOV

 ip INC

 t w iLOAD

 t w MOV

 primitive t SUB

 t -if w iJMP then ( jump straight to VM functions )

 ++rp

 ip {rp} iSTORE

 w ip MOV vm a-optim

 vm JMP

assembler.1 -order

:m header >in @ thead >in ! ;m

:m :ht ( "name" -- : forth routine, no header )

 get-current >r target.1 set-current create

 r> set-current $BABE talign there ,

 does> @ 2/ t, ;m

:m :t header :ht ;m ( "name" -- : forth routine )

:m :to ( "name" -- : forth, target only routine )

 header

 get-current >r target.only.1 set-current create r> set-current

 $BABE talign there ,

 does> @ 2/ t, ;m

:m :a ( "name" -- : assembly routine, no header )

 D00D

 target.1 +order definitions

 create talign there , assembler.1 +order does> @ 2/ t, ;m

:m (a); D00D <> if abort" unstructured" then assembler.1 -order ;m

:m ;a (a); vm a-optim vm JMP ;m

:m postpone target.only.1 +order t' target.only.1 -order 2/ t, ;m

\ NB. There are some bugs with the comparison operators "op<" and "op>" when

\ they deal with extreme values like "$8000 1 <", "$8002 1 <" words fine.

:a bye HALT ;a

:a 1- tos DEC ;a

:a 1+ tos INC ;a

:a invert tos INV ;a

:a [@] tos tos iLOAD ;a

:a [!] w {sp} iLOAD w tos iSTORE --sp tos {sp} iLOAD --sp ;a

:a opEmit tos PUT tos {sp} iLOAD --sp ;a

:a opPush ++sp tos {sp} iSTORE tos ip iLOAD ip INC ;a

:a opSwap tos w MOV tos {sp} iLOAD w {sp} iSTORE ;a

:a opDup ++sp tos {sp} iSTORE ;a

:a opOver w {sp} iLOAD ++sp tos {sp} iSTORE w tos MOV ;a

:a opDrop tos {sp} iLOAD --sp ;a

:a opToR ++rp tos {rp} iSTORE tos {sp} iLOAD --sp ;a

:a opFromR ++sp tos {sp} iSTORE tos {rp} iLOAD --rp ;a

:a opMul w {sp} iLOAD t ZERO

  begin w while tos t ADD w DEC repeat t tos MOV --sp ;a

:a opExit ip {rp} iLOAD --rp ;a

:a - w {sp} iLOAD tos w SUB w tos MOV --sp ;a

:a + w {sp} iLOAD w tos ADD --sp ;a

:a r@ ++sp tos {sp} iSTORE tos {rp} iLOAD ;a

:a rdrop --rp ;a

:a sp@ ++sp tos {sp} iSTORE {sp} tos MOV tos INC ;a

:a sp! tos {sp} MOV ;a

:a rp@ ++sp tos {sp} iSTORE {rp} tos MOV ;a

:a rp! tos {rp} MOV tos {sp} iLOAD --sp ;a

:a opNext w {rp} iLOAD

  w if w DEC w {rp} iSTORE t ip iLOAD t ip MOV vm JMP then ip INC --rp ;a

:a lsb

   tos tos ADD tos tos ADD tos tos ADD tos tos ADD

   tos tos ADD tos tos ADD tos tos ADD tos tos ADD

   tos tos ADD tos tos ADD tos tos ADD tos tos ADD

   tos tos ADD tos tos ADD

   tos w MOV 0 tos MOV w if neg1 tos MOV then ;a

:a opJump ip ip iLOAD ;a

:a opJumpZ

 tos w MOV 0 t MOV w if neg1 t MOV then w DEC w +if neg1 t MOV then

 tos {sp} iLOAD --sp t if ip INC vm JMP then w ip iLOAD w ip MOV ;a

:a op0> tos w MOV 0 tos MOV w +if neg1 tos MOV then ;a

:a op0=

  tos w MOV neg1 tos MOV w if 0 tos MOV then w DEC w +if 0 tos MOV then ;a

:a op0<

  tos w MOV 0 tos MOV w -if neg1 tos MOV then w INC w -if neg1 tos MOV then ;a

:a op< w {sp} iLOAD --sp tos w SUB 0 tos MOV w -if neg1 tos MOV then ;a

:a op> w {sp} iLOAD --sp tos w SUB 0 tos MOV w +if neg1 tos MOV then ;a

:a op2* tos tos ADD ;a

:a op2/

 bwidth w MOV

 x ZERO

 begin w DEC w while

   x x ADD

 tos bt MOV 0 bl1 MOV bt -if neg1 bl1 MOV then bt INC bt -if neg1 bl1 MOV then

   bl1 if x INC then

   tos tos ADD

 repeat

 x tos MOV ;a

:a rshift

 bwidth w MOV

 tos w SUB

 tos {sp} iLOAD --sp

 x ZERO

 begin w while

   x x ADD

 tos bt MOV 0 bl1 MOV bt -if neg1 bl1 MOV then bt INC bt -if neg1 bl1 MOV then

   bl1 if x INC then

   tos tos ADD

   w DEC

 repeat

 x tos MOV ;a

:a opOr

 bwidth w MOV

 x ZERO

 t {sp} iLOAD

 --sp

 begin w while

  x x ADD

tos bt MOV 0 bl1 MOV bt -if neg1 bl1 MOV then bt INC bt -if neg1 bl1 MOV then

t   bt MOV 0 bl2 MOV bt -if neg1 bl2 MOV then bt INC bt -if neg1 bl2 MOV then

  bl1 bl2 ADD bl2 if x INC then

  t t ADD

  tos tos ADD

  w DEC

 repeat

 x tos MOV ;a

:a opXor

 bwidth w MOV

 x ZERO

 t {sp} iLOAD

 --sp

 begin w while

  x x ADD

tos bt MOV 0 bl1 MOV bt -if neg1 bl1 MOV then bt INC bt -if neg1 bl1 MOV then

t   bt MOV 0 bl2 MOV bt -if neg1 bl2 MOV then bt INC bt -if neg1 bl2 MOV then

  bl1 bl2 ADD bl2 INC one bl1 MOV bl2 if 0 bl1 MOV then bl1 x ADD

  t t ADD

  tos tos ADD

  w DEC

 repeat

 x tos MOV ;a

:a opAnd

 bwidth w MOV

 x ZERO

 t {sp} iLOAD

 --sp

 begin w while

  x x ADD

tos bt MOV 0 bl1 MOV bt -if neg1 bl1 MOV then bt INC bt -if neg1 bl1 MOV then

t   bt MOV 0 bl2 MOV bt -if neg1 bl2 MOV then bt INC bt -if neg1 bl2 MOV then

  bl1 bl2 ADD two bl2 ADD one bl1 MOV bl2 if 0 bl1 MOV then bl1 x ADD

  t t ADD

  tos tos ADD

  w DEC

 repeat

 x tos MOV ;a

there 2/ primitive t!

:m ;t $BABE <>

    if abort" unstructured" then talign opExit target.only.1 -order ;m

:m :s tlast @ {system} t@ tlast ! $F00D :t drop 0 ;m

:m :so  tlast @ {system} t@ tlast ! $F00D :to drop 0 ;m

:m ;s drop $BABE ;t $F00D <> if abort" unstructured" then

  tlast @ {system} t! tlast ! ;m

:m :r tlast @ {root-voc} t@ tlast ! $F00D :t drop 0 ;m

:m ;r drop $BABE ;t $F00D <> if abort" unstructured" then

  tlast @ {root-voc} t! tlast ! ;m

:m lit         opPush t, ;m

:m [char] char opPush t, ;m

:m char   char opPush t, ;m

:m begin talign there ;m

:m until talign opJumpZ 2/ t, ;m

:m again talign opJump  2/ t, ;m

:m if opJumpZ there 0 t, ;m

:m mark opJump there 0 t, ;m

:m then there 2/ swap t! ;m

:m else mark swap then ;m

:m while if ;m

:m repeat swap again then ;m

:m aft drop mark begin swap ;m

:m next talign opNext 2/ t, ;m

:m for opToR begin ;m

:m =push   [ t' opPush  half ] literal ;m

:m =jump   [ t' opJump  half ] literal ;m

:m =jumpz  [ t' opJumpZ half ] literal ;m

:m =unnest [ t' opExit  half ] literal ;m

:m =>r     [ t' opToR   half ] literal ;m

:m =next   [ t' opNext  half ] literal ;m

:m dup opDup ;m

:m drop opDrop ;m

:m over opOver ;m

:m swap opSwap ;m

:m >r opToR ;m

:m r> opFromR ;m

:m 0> op0> ;m

:m 0= op0= ;m

:m 0< op0< ;m

:m < op< ;m

:m > op> ;m

:m or opOr ;m

:m xor opXor ;m

:m and opAnd ;m

:m exit opExit ;m

:m 2/ op2/ ;m

:ht #0 0 lit ;t

:ht #1 1 lit ;t

:ht #-1 FFFF lit ;t

:to 1+ 1+ ;t

:to 1- 1- ;t

:to + + ;t

:to - - ;t

:to invert invert ;t

:to bye bye ;t

:to dup dup ;t

:to drop opDrop ;t

:to over opOver ;t

:to swap opSwap ;t

:to rshift rshift  ;t

:so [@] [@] ;s

:so [!] [!] ;s

:so lsb lsb ;s

:to sp@ sp@ ;t

:to sp! sp! ;t

:to 0> op0> ;t

:to 0= op0= ;t

:to 0< op0< ;t

:to < op< ;t

:to > op> ;t

:to 2/ op2/ ;t

:to or opOr ;t

:to xor opXor ;t

:to and opAnd ;t

:to * opMul ;t

:t nop ;t

:t <ok> {ok} lit ;t

:s <emit> {emit} lit ;s

:s <key>  {key} lit ;s

:s <literal> {literal} lit ;s

:s <cold> {cold} lit ;s

:s <echo> {echo} lit ;s

:t current {current} lit ;t

:t root-voc {root-voc} lit ;t

:t #vocs 8 lit ;t

:t context {context} lit ;t

:t here h half lit [@] ;t

:t base {base} lit ;t

:t dpl {dpl} lit ;t

:t hld {hld} lit ;t

:t bl 20 lit ;t

:t >in {in} lit ;t

:t hex  $10 lit {base} half lit [!] ;t

:t decimal $A lit {base} half lit [!] ;t

:t source TERMBUF lit #tib half lit [@] ;t

:s many #0 {in} half lit [!] ;s

:t state {state} lit ;t

:t ] #-1 {state} half lit [!] ;t

:t [ #0  {state} half lit [!] ;t immediate

:t nip swap drop ;t

:t tuck swap over ;t

:t ?dup dup if dup then ;t

:t rot >r swap r> swap ;t

:t -rot rot rot ;t

:t 2drop drop drop ;t

:t 2dup  over over ;t

:t 0<= 0> 0= ;t

:t 0<> 0= 0= ;t

:t = - 0= ;t

:t <> = 0= ;t

:t >= < 0= ;t

:t <= > 0= ;t

:t 0>= 0< 0= ;t

:t negate 1- invert ;t

:t s>d dup 0< ;t

:t abs s>d if negate then ;t

:t 2* op2* ;t

:t cell 2 lit ;t

:t cell+ cell + ;t

:t cells op2* ;t

:t u< 2dup 0< 0= swap 0< 0= <> >r < r> <>  ;t

:t u> swap u< ;t

:t u>= u< 0= ;t

:t u<= u> 0= ;t

:t execute 2/ >r ;t

:t key? #-1 [@] negate s>d if

     {options} half lit [@] 8 lit and if bye then drop #0 exit then #-1 ;t

:t key begin {key} half lit [@] execute until ;t

:t emit {emit} half lit [@] execute ;t

:t cr =cr lit emit =lf lit emit ;t

:t @ 2/ [@] ;t

:t ! 2/ [!] ;t

:t get-current current @ ;t

:t set-current current ! ;t

:s last get-current @ ;s

:t pick sp@ + [@] ;t

:t +! 2/ tuck [@] + swap [!] ;t

:t lshift begin ?dup while 1- swap 2* swap repeat ;t

:t c@ dup @ swap lsb if 8 lit rshift else $FF lit and then ;t

:t c!  swap $FF lit and dup 8 lit lshift or swap

  tuck dup @ swap lsb 0= $FF lit xor

  >r over xor r> and xor swap ! ;t

:t max 2dup < if nip else drop then ;t

:t min 2dup > if nip else drop then ;t

:t count dup 1+ swap c@ ;t

:s logical 0<> if #1 else #0 then ;s

:t aligned dup lsb logical + ;t

:t align here aligned h half lit [!] ;t

:t +string #1 over min rot over + rot rot - ;t

:t type begin dup while swap count emit swap 1- repeat 2drop ;t

:t cmove for aft >r dup c@ r@ c! 1+ r> 1+ then next 2drop ;t ( b1 b2 u -- )

:t fill  swap for swap aft 2dup c! 1+ then next 2drop ;t     ( b u c -- )

:t erase #0 fill ;t ( NB. blank is bl fill )

:s do$ r> r> 2* dup count + aligned 2/ >r swap >r ;s ( -- a : )

:s ($) do$ ;s            ( -- a : do string NB. )

:s .$ do$ count type ;s  ( -- : print string, next cells contain string )

:m ." .$ $literal ;m

:m $" ($) $literal ;m

:t space bl emit ;t

:t catch        ( xt -- exception# | 0 \ return addr on stack )

  sp@ >r                        ( xt )   \ save data stack pointer

  {handler} half lit [@] >r     ( xt )   \ and previous handler

  rp@ {handler} half lit [!]    ( xt )   \ set current handler

  execute                       ( )      \ execute returns if no throw

  r> {handler} half lit [!]     ( )      \ restore previous handler

  rdrop                         ( )      \ discard saved stack ptr

  #0 ;t                         ( 0 )    \ normal completion

:t throw ( ??? exception# -- ??? exception# )

   ?dup if                      ( exc# )     \ 0 throw is no-op

     {handler} half lit [@] rp! ( exc# )     \ restore prev return stack

     r> {handler} half lit [!]  ( exc# )     \ restore prev handler

     r> swap >r                 ( saved-sp ) \ exc# on return stack

     sp! drop r>                ( exc# )     \ restore stack

   then ;t

:t abort #-1 throw ;t

:s (abort) do$ swap if count type abort then drop ;s

:t um+

 2dup + >r r@ #0 >= >r 2dup and 0< r> or >r or 0< r> and invert 1+ r> swap ;t

:t dnegate invert >r invert #1 um+ r> + ;t ( d -- d )

:t d+ >r swap >r um+ r> + r> + ;t         ( d d -- d )

:t um* ( u u -- ud : double cell width multiply )

 #0 swap ( u1 0 u2 ) $F lit

 for

   dup um+ >r >r dup um+ r> + r>

   if >r over um+ r> + then

 next rot drop ;t

:t um/mod ( ud u -- ur uq : unsigned double cell width divide/modulo )

 ?dup 0= if -A lit throw then

 2dup u<

 if negate $F lit

   for >r dup um+ >r >r dup um+ r> + dup

     r> r@ swap >r um+ r> ( or -> ) 0<> swap 0<> +

     if >r drop 1+ r> else drop then r>

   next

   drop swap exit

 then 2drop drop #-1 dup ;t

:t m/mod ( d n -- r q : floored division )

 s>d dup >r

 if

   negate >r dnegate r>

 then

 >r s>d if r@ + then r> um/mod r>

 if swap negate swap exit then ;t

:t /mod  over 0< swap m/mod ;t

:t mod  /mod drop ;t

:t /    /mod nip ;t

:s depth {sp0} half lit [@] sp@ - 1- ;s

:s (emit) opEmit ;s

:t echo {echo} half lit [@] execute ;t

:s tap dup echo over c! 1+ ;s ( bot eot cur c -- bot eot cur )

:s ktap ( bot eot cur c -- bot eot cur )

 dup dup =cr lit <> >r  =lf lit <> r> and if ( Not End of Line? )

   dup =bksp lit <> >r =del lit <> r> and if ( Not Delete Char? )

     bl tap

     exit

   then

   >r over r@ < dup if

     =bksp lit dup echo bl echo echo

   then

   r> +

   exit

 then drop nip dup ;s

:t accept ( b u -- b u : read in a line of user input )

 over + over begin

   2dup <>

 while

   key dup bl - $5F lit u< if tap else ktap then

 repeat drop over - ;t

:t query TERMBUF lit =buf lit accept #tib lit ! drop #0 >in ! ;t

:s ?depth depth > if -4 lit throw then ;s ( u -- : check stack depth )

:t -trailing for aft bl over r@ + c@ < if r> 1+ exit then then next #0 ;t

:s look ( b u c xt -- b u : skip until *xt* test succeeds )

 swap >r rot rot

 begin

   dup

 while

   over c@ r@ - r@ bl = 4 lit pick execute

   if rdrop rot drop exit then

   +string

 repeat rdrop rot drop ;s

:s unmatch if 0> exit then 0<> ;s ( c1 c2 -- t )

:s match unmatch invert ;s        ( c1 c2 -- t )

:t parse ( c -- b u ; <string> )

   >r source drop >in @ + #tib lit @ >in @ - r@

   >r over r> swap >r >r

   r@ t' unmatch lit look 2dup

   r> t' match   lit look swap r> - >r - r> 1+  ( b u c -- b u delta )

   >in +!

   r> bl = if -trailing then #0 max ;t

:t spaces begin dup 0> while space 1- repeat drop ;t ( +n -- )

:t hold #-1 hld +! hld @ c! ;t ( c -- : save a character in hold space )

:t #> 2drop hld @ =tbufend lit over - ;t  ( u -- b u )

:s extract dup >r um/mod r> swap >r um/mod r> rot ;s ( ud ud -- ud u )

:s digit 9 lit over < 7 lit and + [char] 0 + ;s ( u -- c )

:t #  2 lit ?depth #0 base @ extract digit hold ;t ( d -- d )

:t #s begin # 2dup ( d0= -> ) or 0= until ;t       ( d -- 0 )

:t <# =tbufend lit hld ! ;t                        ( -- )

:t sign 0< if [char] - hold then ;t                ( n -- )

:t u.r >r #0 <# #s #>  r> over - spaces type ;t

:t u.     #0 <# #s #> space type ;t

:t . dup >r abs #0 <# #s r> sign #> space type ;t  ( n -- print number )

:t >number ( ud b u -- ud b u : convert string to number )

 begin

   2dup >r >r drop c@ base @        ( get next character )

   ( digit? -> ) >r [char] 0 - 9 lit over <

   if 7 lit - dup $A lit < or then dup r> u< ( c base -- u f )

   0= if                            ( d char )

     drop                           ( d char -- d )

     r> r>                          ( restore string )

     exit                           ( ..exit )

   then                             ( d char )

   swap base @ um* drop rot base @ um* d+ ( accumulate digit )

   r> r>                            ( restore string )

   +string dup 0=                   ( advance string and test for end )

 until ;t

:t number? ( a u -- d -1 | a u 0 : string to a number [easier to use] )

 #-1 dpl !

 base @ >r

 over c@ [char] - = dup >r if     +string then

 over c@ [char] $ =        if hex +string then

 >r >r #0 dup r> r>

 begin

   >number dup

 while over c@ [char] . <>

   if rot drop rot r> 2drop #0 r> base ! exit then

   1- dpl ! 1+ dpl @

 repeat

 2drop r> if dnegate then r> base ! #-1 ;t

:t compare ( a1 u1 a2 u2 -- n : string equality )

 rot

 over - ?dup if >r 2drop r> nip exit then

 for ( a1 a2 )

   aft

     count rot count rot - ?dup

     if rdrop nip nip exit then

   then

 next 2drop #0 ;t

:t .s depth for aft r@ pick . then next ;t

:t nfa cell+ ;t ( pwd -- nfa : move word pointer to name field )

:t cfa nfa dup c@ $1F lit and + cell+ cell negate and ;t ( pwd -- cfa )

:t allot aligned h lit +! ;t

:t , align here ! cell allot ;t

:s (search-wordlist) ( a wid -- PWD PWD 1|PWD PWD -1|0 a 0: find word in WID )

 swap >r dup

 begin

   dup

 while

   dup nfa count $9F lit ( $1F:word-length + $80:hidden )

   and r@ count compare 0=

   if ( found! )

     rdrop

     dup ( immediate? -> ) nfa $40 lit swap @ and 0<>

     #1 or negate exit

   then

   nip dup @

 repeat

 rdrop 2drop #0 ;s

:s (find) ( a -- pwd pwd 1 | pwd pwd -1 | 0 a 0 : find a word dictionary )

 >r

 context

 begin

   dup @

 while

   dup @ @ r@ swap (search-wordlist) ?dup

   if

     >r rot drop r> rdrop exit

   then

   cell+

 repeat drop #0 r> #0 ;s

:t search-wordlist (search-wordlist) rot drop ;t ( a wid -- PWD 1|PWD -1|a 0 )

:t find ( a -- pwd 1 | pwd -1 | a 0 : find a word in the dictionary )

 (find) rot drop ;t

:s (literal) state @ if =push lit , , then ;s

:t literal <literal> @ execute ;t immediate ( u -- )

:t compile, 2/ align , ;t  ( xt -- )

:s ?found

  if exit then space count type [char] ? emit cr -D lit throw ;s ( u f -- )

:t interpret ( b -- )

 find ?dup if

   state @

   if

     0> if cfa execute exit then \ <- immediate word are executed

     cfa compile, exit           \ <- compiling word are...compiled.

   then

   drop

   dup nfa c@ 20 lit and if -E lit throw then ( <- ?compile )

   cfa execute exit  \ <- if its not, execute it, then exit *interpreter*

 then

 \ not a word

 dup >r count number? if rdrop \ it is a number!

   dpl @ 0< if \ <- dpl will be -1 if it is a single cell number

      drop     \ drop high cell from 'number?' for single cell output

   else        \ <- dpl is not -1, it is a double cell number

      state @ if swap then

      postpone literal \ literal is executed twice if it's a double

   then

   postpone literal exit

 then

 r> #0 ?found ;t \ Could vector ?found here, to handle arbitrary words

:s .id nfa count $1F lit and type space ;s ( pwd -- : print out a word )

:t get-order ( -- widn ... wid1 n : get the current search order )

 context

 ( find empty cell -> ) #0 >r begin dup @ r@ xor while cell+ repeat rdrop

 dup cell - swap

 context - 2/ dup >r 1- s>d if -50 lit throw then

 for aft dup @ swap cell - then next @ r> ;t

:r set-order ( widn ... wid1 n -- : set the current search order )

 dup #-1 = if drop root-voc #1 set-order exit then ( NB. Recursion! )

 dup #vocs > if -49 lit throw then

 context swap for aft tuck ! cell+ then next #0 swap ! ;r

:r forth-wordlist {forth-wordlist} lit ;r ( -- wid )

:r system {system} lit ;r ( -- wid )

:r forth root-voc forth-wordlist 2 lit set-order ;r ( -- )

:r only #-1 set-order ;r                            ( -- )

:r words

 get-order begin ?dup while swap dup cr u. ." : " @

   begin ?dup while dup nfa c@ $80 lit and 0= if dup .id then @ repeat cr

 1- repeat ;r

:t definitions context @ set-current ;t

:t (order) ( w wid*n n -- wid*n w n )

 dup if

   1- swap >r (order) over r@ xor

   if

     1+ r> -rot exit

   then rdrop

 then ;t

:t -order get-order (order) nip set-order ;t

:t +order dup >r -order get-order r> swap 1+ set-order ;t

:t word parse here dup >r 2dup ! 1+ swap cmove r> ;t ( c -- b )

:s ?unique ( a -- a : print a message if a word definition is not unique )

dup get-current (search-wordlist) 0= if exit then space

2drop {last} lit @ .id ." redefined" cr ;s

:s ?nul dup c@ if exit then -10 lit throw ;s

:to char bl word ?nul count drop c@ ;t

:to [char] postpone char =push lit , , ;t immediate

:to ; $BABE lit <> if -16 lit throw then =unnest lit , postpone [

?dup if get-current ! exit then ;t immediate compile-only ( -- wid )

:to : align here dup {last} lit ! ( "name", -- colon-sys )

 last , bl word ?nul ?unique count + h lit ! align $BABE lit postpone ] ;t

:to :noname here $BABE lit ] ;t

:to begin align here ;t immediate compile-only

:to until =jumpz lit , 2/ , ;t immediate compile-only

:to again =jump  lit , 2/ , ;t immediate compile-only

:to if =jumpz lit , here #0 , ;t immediate compile-only

:to then here 2/ swap ! ;t immediate compile-only

:to while postpone if ;t immediate compile-only

:to repeat swap postpone again postpone then ;t immediate compile-only

:to else =jump lit , here #0 , swap postpone then ;t immediate compile-only

:to for =>r lit , here ;t immediate compile-only

:to aft drop =jump lit , here #0 , align here swap ;t immediate compile-only

:to next =next lit , 2/ , ;t immediate compile-only

:to ' bl word find ?found cfa literal ;t immediate

:t compile r> dup [@] , 1+ >r ;t compile-only

:t recurse {last} lit @ cfa compile, ;t immediate compile-only

:s toggle tuck @ xor swap ! ;s

:s hide bl word find ?found nfa $80 lit swap toggle ;s

:s (var) r> 2* ;s compile-only

:s (const) r> [@] ;s compile-only

:s (marker) r> 2* dup @ h lit ! cell+ @ get-current ! ;s compile-only

:t create postpone : drop postpone [ compile (var) get-current ! ;t

:to variable create #0 , ;t

:to constant create cell negate allot compile (const) , ;t

:to marker last here create cell negate allot compile (marker) , , ;t

:t >body cell+ ;t ( a -- a )

:s (does) r> r> 2* swap >r ;s compile-only

:s (comp) r> {last} lit @ cfa ! ;s compile-only

:t does> compile (comp) compile (does) ;t immediate compile-only

:to rp! compile rp! ;t immediate compile-only

:to rp@ compile rp@ ;t immediate compile-only

:to >r compile opToR ;t immediate compile-only

:to r> compile opFromR ;t immediate compile-only

:to r@ compile r@ ;t immediate compile-only

:to rdrop compile rdrop ;t immediate compile-only

:to exit compile opExit ;t immediate compile-only

:to ." compile .$

 [char] " word count + h half lit [!] align ;t immediate compile-only

:to $" compile ($)

 [char] " word count + h half lit [!] align ;t immediate compile-only

:to abort" compile (abort)

 [char] " word count + h half lit [!] align ;t immediate compile-only

:to ( [char] ) parse 2drop ;t immediate

:to .( [char] ) parse type ;t immediate

:to postpone bl word find ?found cfa compile, ;t immediate

:to ) ;t immediate

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[theflounderingimmunologist]

TNFa promotes dephosphorylation of Foxp3 in rheumatoid arthritis

Tregs found in RA-synovial fluid (RA-SF) from patients in equal proportions compared to healthy SF and patient PBMC but are less suppressive in in vitro assays. - inhibition of suppressive capacity increases with increasing doses of RA-SF in culture. - effect replicated with TNFa alone but not other inflammatory cytokines found in RA-SF.

RA-SF Tregs express Foxp3 at similar level as normal Tregs but are less phosphorylated (by pSer/Tyr western) - phosphorylation is inhibited by RA-SF and TNFa.  - by site-directed mutagenesis, Ser418 identified as phosphorylation site required for full Treg activity.

TNFa signalling through NFkB upregulates PP1 phosphatase expression --> increased dephosphorylation of Ser418. - Ser418 is in C-terminal DNA-binding helix domain: phosphorylation may be required for adequate binding (adjacent lysine residues are acetylated). - Ser418 dephophorylation (or mutation to alanine S418A) increases IL-2 production, S418E (phosphoserine mimetic) decreases slightly compared to WT. 

Anti-TNFa therapy (infliximab) in human RA patients restores Foxp3 phosphorylation and suppressive function.

Fig 3

INTERESTING: Draws attention to the role of post-transcriptional modification in modulating Foxp3 function. What event/kinase drives Foxp3 phosphorylation upon activation? Are there other phosphorylation sites which modulate Treg suppression? NOTE: relevance for PI3K inhibition!

Source: Nie, Hong (Zhang, Jingwu) 2013, Nature Medicine. Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis http://www.nature.com/nm/journal/v19/n3/full/nm.3085.html

[vedamayurveda]

Psoriatic Arthritis Treatment in Bangalore

If you are looking for psoriatic arthritis treatment in Bangalore, there are a few different options to choose from. One popular choice is vedamayurveda, which is considered one of the best forms of treatment for psoriatic arthritis. After diagnosis, your doctor will explain the options and discuss them with you. You may also opt for alternative therapy like acupuncture, which is an excellent way to avoid pain-inducing medicines.

Rheumatology doctors in Bangalore are highly skilled in treating various forms of arthritis, and can prescribe advanced therapies that target specific parts of the immune system. Treatment plans are customized to alleviate pain, decrease joint damage, and improve overall function. Your doctor will most likely recommend taking biologics, which are drugs that target specific parts of the body's immune system. However, biologics are not inexpensive, and they can only be used in specific cases.

Biologics are complicated drugs that work by blocking the immune system's signals. They are given via injection or infusion. There are two main types of biologics used to treat psoriatic arthritis. The first type, known as anti-tumor necrosis factor-alpha (anti-TNFA), blocks a signal produced by immune cells that cause inflammation. In addition, these drugs block the production of two other proteins called interleukin-12 and interleukin-23. While biologics are effective for psoriatic arthritis, they do suppress the immune system and increase the risk of infection.

Vedam Ayurveda psoriasis treatment in Bengaluru focuses on the use of herbal remedies. Ayurvedic psoriasis treatment in Bengaluru includes Triphala, which is made from three fruits and helps cleanse the body by regulating bowel movements. Turmeric also helps in detoxifying the body and is a common psoriasis remedy.

In addition to using topical medications, many doctors in Bangalore also practice a holistic approach to the treatment of psoriasis. Topical medication is used for mild forms of the disease, while phototherapy is an option for more severe cases. If your condition has spread to your hands or feet, you should visit a dermatologist for a consultation. A holistic approach to psoriasis treatment in Bangalore may be the best option for you.

Alternative medicine doctors often use Ayurveda as a form of treatment for psoriatic arthritis. In ayurveda, an imbalance between the four main energy systems in the body can lead to diseases. The joints, for instance, are areas where Vata and Kapha mix. By using herbal medicines and therapies, a holistic treatment can address the underlying cause of the disease.

Psoriatic arthritis is a chronic form of arthritis. It can range from mild with intermittent flare-ups to a severe form that can damage joints. To avoid this, early diagnosis is critical. Most people with this disease also have skin psoriasis, so early diagnosis is critical. The disease generally affects the large joints such as the spine and the sacroiliac joints in the pelvis. Other areas of the body affected by psoriatic arthritis include the nails and tendons.

[examiningepsteinbarrvirus]

Abstract

In 2020, over 19.3 million new cancer cases were diagnosed worldwide and approximately 15 percent of all human cancers worldwide were attributed to viruses. The Epstein Barr Virus (EBV) infects approximately 95 percent of all adults and causes ~ 1% of all cancers. 

This project pioneers the examination of the role of EBV in nasopharyngeal cancer using single-cell RNA sequencing (scRNA-seq). 

Cancer stem cells (CSC) are a heterogenous subpopulation within tumors that have self-renewal and differentiation properties potentially causing tumor initiation and relapses. CSCs are crucial for novel anti-cancer drug discovery.

 In order to investigate the cellular response to EBV infection at the single-cell level in nasopharyngeal cancer (NPC) patients, I sourced a dataset containing tumor and peripheral blood mononuclear cell (PBMC) samples. To visualize the high dimensional data in a 2D map, we used the uniform manifold approximation and projection algorithm (UMAP), a neighbor graph-based approach to identify the cell identities. 

After checking the expression of all EBV genes, we identified LMP-1 as the sole EBV gene detected. We identified major pathways associated with human cancer malignancy, hallmark TNFA signaling via NFKB pathway, hypoxia pathway, and hallmark p53 pathway. Based on our analysis, we observed that the SOX9 gene and CD44 gene were more expressed in LMP-1 high cells versus low cells. These cancer stem cell genes were overrepresented in high LMP-1 cells than the control. By targeting LMP-1 expressing stem-like cancer cells, this research has the potential to lead to an improved outcome when combined with other treatments. 

[biomedgrid]

Biomed Grid | Innate Immune System in Chronic Endometritis Quota?

Background

The innate immune system is one of the two main immunity strategies found in human [1-2]. Unlike adaptive immunity, the innate immune responses are not specific to a particular pathogen and recognize some general groups of proteins and phagocytic cells. The major function of the innate immune system is to maintain the human body homeostasis and genetic identity by protecting the host from the toxins, infectious agents and endogenous cell waste products [3, 4, 5]. The critical role in the regulation of the innate immunity belongs to proteins of the Toll-like superfamily that express both intra- and extracellular and induce cytokines and interferons productions [6, 7, 8]. This study set out to investigate the innate immunity factors expression in the endometrium of women diagnosed with chronic endometritis.

Materials and Methods

This investigation takes the form of a prospective case-study of 43 patients aged 34,4 ± 2,7 years old. Criteria for selecting the subjects were as follows: chronic endometritis approved by histology and immunohistochemistry; absence of sexually transmitted infections; absence of severe somatic diseases; received informed consent to participate in the study. A comparison group includes 15 healthy women with BMI from 19 to 24 kg/m2 without any history of pregnancies, sexually transmitted infections, uterine interventions, and severe gynecological or other somatic diseases. The first step in the study was to conduct the endometrial aspirational pipelle biopsy (on 20-24 days of the menstrual cycle) and the morphological and immunohistochemical examination of samples with an assessment of CD138 (B-A138, syndecan-1 Roche-Ventana), CD20, CD8, CD4, CD56 (123C3 Roche-Ventana), and HLA-DRII. After that, in order to analyze the expression TLR-4, TLR-2, HBD1-defensin и TNFa genes, the Real Time-PCR and the reverse transcription reaction were run. To measure the HNP1-3 antimicrobial peptide levels, the enzyme-linked immunosorbent assay (ELISA) was used (Human HNP1-3, HycultBiotech).

Statistical Analysis

Data management and analysis were performed using Microsoft Excel 2016 and Statistica 6.1. Means reflecting conditions before and after the treatment were compared using the Wilcoxon signedrank test. Results were considered to be significant when p<0,01.

Results

Compared to the healthy women group, rates of Epstein – Barr virus identification in endometrium were significantly higher in the group of women diagnosed with chronic endometritis (in 55,8%). Besides from the Epstein – Barr virus, a significant increase in activity of CD138 (detected in 82,8% in study group comparing to 5,2% in the group of the healthy women), CD20 (in 53,5% comparing to 6,9%), CD8 (in 58,8% comparing to 4,7%), CD4 (in 59,2% comparing to 9,3%), CD56 (in 51,2% comparing to 9,3%), and HLA-DRII (in 55,8% comparing to 6,9%) was found in endometrial samples with chronic endometritis. Regarding the innate immune system proteins genes, their activity was variable in the endometrium of healthy women and women with chronic endometritis. Analyzing the two groups, a significant up-regulation of TNF and TLR-2 genes expression (2517,9±413,1 x103 copies/ ml and 1481,5±216,2 х103 copies/ml respectively comparing to 2218,7±305,2 х103 copies/ml and 1225,6±109,2 х103 copies/ml respectively in healthy women group) and a down-regulation in TLR- 4 and HBD-1 genes expression (376,5 ±103,2 х103 copies/ml and 1013,7±211х103 copies/ml respectively comparing to 610,7±94,2 х103 copies/ml and 1354,7±199,2 х103 copies/ml respectively in healthy women group) was found in the endometrium of women diagnosed with chronic endometritis. The HNP1-3 gene activity was absent in healthy endometrium, while its activity in tissue with chronic endometritis was up-regulated, resulting in the production of significant amounts of protein (7,3±1,1 ng/ml).

Conclusion

One of the more significant findings to emerge from this study is that the cell types prevail in the endometrium with chronic endometritis are plasmatic cells (CD138), B-lymphocytes, large granular lymphocytes (CD56) and T-helpers (CD4). Also, analysis of such samples revealed a presence of chronic viral infections, whereas the Epstein – Barr virus was the most common one (identified in 55,8%). Chronic endometritis is a pathological condition involving the breakdown of balance between immunocompetent cells and cytokines, leading to disrupt in receptiveness and proliferative activity of cells. This study has approved the immunological disbalance occurring in the endometrial tissue in the state of chronic inflammation.

Read More About this Article: https://biomedgrid.com/fulltext/volume6/innate-immune-system-in-chronic-endometritis.001020.php

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