Enriched characteristics of poultry collagen over other sources of collagen and its extraction methods: A review.

Collagen is the most abundant protein in animals and is extensively studied for its structural and thermal stability, biocompatibility, and healing properties which enables them to be widely applied in various fields. Collagen extracted from poultry sources have shown improved structural stability and reduced risk of triggering allergic responses and transmitting animal diseases onto humans. Furthermore, poultry collagen is widely accepted by consumers of diverse beliefs in comparison to collagen extracted from bovine and porcine sources. The review aims to compare different sources of collagen, focusing on the various beneficial characteristics of poultry collagen over the other sources. Moreover, the review explains various pre-treatment and extraction methods of poultry collagen and its versatile applications in different industrial sectors.

The impact of the human gut microbiome on the treatment of autoimmune disease.

Autoimmune (or rheumatic) diseases are increasing in prevalence but selecting the best therapy for each patient proceeds in trial-and-error fashion. This strategy can lead to ineffective therapy resulting in irreversible damage and suffering; thus, there is a need to bring the promise of precision medicine to patients with autoimmune disease. While host factors partially determine the therapeutic response to immunosuppressive drugs, these are not routinely used to tailor therapy. Thus, non-host factors likely contribute. Here, we consider the impact of the human gut microbiome in the treatment of autoimmunity. We propose that the gut microbiome can be manipulated to improve therapy and to derive greater benefit from existing therapies. We focus on the mechanisms by which the human gut microbiome impacts treatment response, provide a framework to interrogate these mechanisms, review a case study of a widely-used anti-rheumatic drug, and discuss challenges with studying multiple complex systems: the microbiome, the human immune system, and autoimmune disease. We consider open questions that remain in the field and speculate on the future of drug-microbiome-autoimmune disease interactions. Finally, we present a blue-sky vision for how the microbiome can be used to bring the promise of precision medicine to patients with rheumatic disease.

Silver sulphide nanoparticles (Ag2SNPs) synthesized using Phyllanthus emblica fruit extract for enhanced antibacterial and antioxidant properties.

In this study, silver sulfide nanoparticles (Ag2SNP's) were successfully produced by using fruit extracts of Phyllanthus emblica. UV-vis, FTIR, XRD with SEM and EDX techniques were used for the synthesis process and for characterization of the resulting nanostructures. According to the findings, the fabricated nanostructure had a monoclinic crystal structure, measuring 44 nm in grain size, and its strain was 1.82 × 10-3. As revealed by SEM analysis, the synthesized nanostructure consists of irregular spherical and triangular shapes. The presence of silver (Ag) and sulfur (S) was also confirmed through EDX spectra. Furthermore, Ag2S nanoparticles were tested for their ability to effectively inhibit gram-positive and gram-negative bacterial growth. As a result of this study, it was clearly demonstrated that Ag2S nanoparticles possess powerful antibacterial properties, particularly when it came to inhibiting Escherichia coli growth. Ag2S nanoparticles had high total H2O2 and flavonoid concentrations and the greatest overall antioxidant activity, according to the evaluation of antioxidant activity of the samples. The results obtained from the P. emblica fruit extract were followed by those obtained from Ag2S nanoparticles were reported in detail. RESEARCH HIGHLIGHTS: Innovative Ag2SNP synthesis using Phyllanthus emblica fruit extract. SEM with EDX revealed a monoclinic crystal structure with a grain size of 44 nm and a strain of 1.82 × 10-3. Many of these applications are demonstrated by the potential of Ag2SNPs to treat and combat bacteria, particularly Escherichia coli. A peak at 653 cm-1 indicates the presence of primary sulfide aliphatic C-S extension vibrations. The abundant H2O2 and NO2 found in P. emblica nanocomposites make them potent antioxidants.

Alteration in the gut microbiome is associated with changes in bone metabolism after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, leads to durable weight loss and improves obesity-related comorbidities. However, it induces abnormalities in bone metabolism. One unexplored potential contributor is the gut microbiome, which influences bone metabolism and is altered after surgery. We characterized the relationship between the gut microbiome and skeletal health in severe obesity and after LSG. In a prospective cohort study, 23 adults with severe obesity underwent skeletal health assessment and stool collection preoperatively and 6 mo after LSG. Gut microbial diversity and composition were characterized using 16S rRNA gene sequencing, and fecal concentrations of short-chain fatty acids (SCFA) were measured with LC-MS/MS. Spearman's correlations and PERMANOVA analyses were applied to assess relationships between the gut microbiome and bone health measures including serum bone turnover markers (C-terminal telopeptide of type 1 collagen [CTx] and procollagen type 1 N-terminal propeptide [P1NP]), areal BMD, intestinal calcium absorption, and calciotropic hormones. Six months after LSG, CTx and P1NP increased (by median 188% and 61%, P < .01) and femoral neck BMD decreased (mean -3.3%, P < .01). Concurrently, there was a decrease in relative abundance of the phylum Firmicutes. Although there were no change in overall microbial diversity or fecal SCFA concentrations after LSG, those with greater within-subject change in gut community microbial composition (ß-diversity) postoperatively had greater increases in P1NP level (ρ = 0.48, P = .02) and greater bone loss at the femoral neck (ρ = -0.43, P = .04). In addition, within-participant shifts in microbial richness/evenness (α-diversity) were associated with changes in IGF-1 levels (ρ = 0.56, P < .01). The lower the postoperative fecal butyrate concentration, the lower the IGF-1 level (ρ = 0.43, P = .04). Meanwhile, the larger the decrease in butyrate concentration, the higher the postoperative CTx (ρ = -0.43, P = .04). These findings suggest that LSG-induced gut microbiome alteration may influence skeletal outcomes postoperatively, and microbial influences on butyrate formation and IGF-1 are possible mechanisms.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, is a highly effective treatment for obesity because it produces dramatic weight loss and improves obesity-related medical conditions. However, it also results in abnormalities in bone metabolism. It is important to understand how LSG affects the skeleton, so that bone loss after surgery might be prevented. We studied adult men and women before and 6 mo after LSG, and we explored the relationship between the altered gut bacteria and bone metabolism changes. We found that: Those with greater shifts in their gut bacterial composition had more bone loss.Butyrate, a metabolite produced by gut bacteria from fermentation of dietary fiber, was associated with less bone breakdown and higher IGF-1 level (a bone-building hormone). We conclude that changes in the gut bacteria may contribute to the negative skeletal impact of LSG and reduced butyrate production by the gut bacteria leading to lower IGF-1 levels is a possible mechanism.

Simvastatin induces human gut bacterial cell surface genes.

Drugs intended to target mammalian cells can have broad off-target effects on the human gut microbiota with potential downstream consequences for drug efficacy and side effect profiles. Yet, despite a rich literature on antibiotic resistance, we still know very little about the mechanisms through which commensal bacteria evade non-antibiotic drugs. Here, we focus on statins, one of the most prescribed drug types in the world and an essential tool in the prevention and treatment of high circulating cholesterol levels. Prior work in humans, mice, and cell culture support an off-target effect of statins on human gut bacteria; however, the genetic determinants of statin sensitivity remain unknown. We confirmed that simvastatin inhibits the growth of diverse human gut bacterial strains grown in communities and in pure cultures. Drug sensitivity varied between phyla and was dose-dependent. We selected two representative simvastatin-sensitive species for more in-depth analysis: Eggerthella lenta (phylum: Actinobacteriota) and Bacteroides thetaiotaomicron (phylum: Bacteroidota). Transcriptomics revealed that both bacterial species upregulate genes in response to simvastatin that alter the cell membrane, including fatty acid biogenesis (E. lenta) and drug efflux systems (B. thetaiotaomicron). Transposon mutagenesis identified a key efflux system in B. thetaiotaomicron that enables growth in the presence of statins. Taken together, these results emphasize the importance of the bacterial cell membrane in countering the off-target effects of host-targeted drugs. Continued mechanistic dissection of the various mechanisms through which the human gut microbiota evades drugs will be essential to understand and predict the effects of drug administration in human cohorts and the potential downstream consequences for health and disease.

SIMMER employs similarity algorithms to accurately identify human gut microbiome species and enzymes capable of known chemical transformations.

Bacteria within the gut microbiota possess the ability to metabolize a wide array of human drugs, foods, and toxins, but the responsible enzymes for these chemical events remain largely uncharacterized due to the time-consuming nature of current experimental approaches. Attempts have been made in the past to computationally predict which bacterial species and enzymes are responsible for chemical transformations in the gut environment, but with low accuracy due to minimal chemical representation and sequence similarity search schemes. Here, we present an in silico approach that employs chemical and protein Similarity algorithms that Identify MicrobioMe Enzymatic Reactions (SIMMER). We show that SIMMER accurately predicts the responsible species and enzymes for a queried reaction, unlike previous methods. We demonstrate SIMMER use cases in the context of drug metabolism by predicting previously uncharacterized enzymes for 88 drug transformations known to occur in the human gut. We validate these predictions on external datasets and provide an in vitro validation of SIMMER's predictions for metabolism of methotrexate, an anti-arthritic drug. After demonstrating its utility and accuracy, we made SIMMER available as both a command-line and web tool, with flexible input and output options for determining chemical transformations within the human gut. We present SIMMER as a computational addition to the microbiome researcher's toolbox, enabling them to make informed hypotheses before embarking on the lengthy laboratory experiments required to characterize novel bacterial enzymes that can alter human ingested compounds.

Post COVID-19 clinical manifestations and its risk factors among patients in a Northern District in Kerala, India.

Background: The novel virus SARS-CoV-2 has caused a pandemic of coronavirus disease 2019 (COVID-19). There is emerging evidence of post-COVID-19 manifestations among patients who sustain acute COVID-19. Most studies report fatigue, dyspnea, and myalgia as the common symptoms; however, currently, there is limited knowledge of these post-COVID manifestations and their risk factors, especially in India. Methods: A descriptive cross-sectional study was conducted among patients who had attended the district post-COVID clinic, Wayanad district, Kerala, from October 2020 to June 2021. Data were collected by direct/telephonic patient interviews and from their existing case records, using a pretested semi-structured proforma. Results: The sample size was 667. The mean age of the study population was 45 years (standard deviation [SD]: 14.55). The majority of the population presented with dyspnea (48%), fatigue (32%), and cough (25.6%). Mental health problems were also reported in 6% of participants. The respiratory system was commonly involved (61.2%). Around one-third of the patients (36.4%) had dyspnea on exertion and 11.8% had dyspnea at rest. One-fifth of the population reported aggravation of pre-existing co-morbidity and half of the respondents had persistence of at least one symptom after 6 months. There exist statistically significant associations between identified risk factors, especially gender, increasing age, the severity of COVID-19 infection, history of tobacco/alcohol use, and co-morbidities with outcomes. Conclusion: As post-COVID syndrome is a multisystem disease, integrated rehabilitation is required with targeted intervention for survivors based on their symptoms and needs.

Determinants and Prognostic Implications of Hepatorenal Dysfunction in Adults With Congenital Heart Disease.

BACKGROUND: There are limited data on the prognostic role of hepatorenal function indices in ambulatory patients with congenital heart disease (CHD). The purpose of this study was to determine the prevalence, risk factors, and prognostic implications of hepatorenal dysfunction, as measured by Model for End-Stage Liver Disease Excluding International Normalised Ratio (MELD-XI) score, in adults with CHD. METHODS: In this retrospective study of CHD patients with comprehensive metabolic panels (2003-2019), mild/moderate and severe hepatorenal dysfunction was defined as MELD-XI 11-15 and > 15, respectively. RESULTS: Of 4977 patients, 1376 (28%) had hepatorenal dysfunction (mild/moderate: n = 935 [19%]; severe: n = 441 [9%]). Hepatorenal dysfunction was most common in Fontan/unrepaired single ventricle (46%) and right heart disease (31%). Baseline MELD-XI was associated with all-cause mortality (HR 1.27, CI 1.21-1.33; P < 0.001) after adjustment for age, sex, and congenital heart lesion. In 3864 patients with serial MELD-XI data, there was a temporal increase in MELD-XI, and this was associated with an increased risk of mortality (HR 1.24, CI 1.15-1.36, per unit increase in MELD-XI; P = 0.004), independently from the baseline MELD-XI score. In the subset of 1856 patients that underwent surgical/transcatheter interventions, there was a postoperative reduction in MELD-XI, and this was associated with a lower risk of mortality (HR 0.94, CI 0.90-0.98, per unit decrease in MELD-XI; P = 0.008), independently from the baseline MELD-XI score. CONCLUSIONS: Hepatorenal dysfunction was common in adults with CHD. Both baseline MELD-XI score and temporal changes in MELD-XI were associated with clinical outcomes, and therefore could be used to monitor therapeutic response to interventions and for deterioration in clinical status.

Improvement in hepatic and renal function following isolated heart transplant in adults with congenital heart disease.

BACKGROUND: There are limited data about postoperative changes in hepatic and renal function in adults with congenital heart disease (CHD) undergoing isolated heart transplant. The purpose of this study was to assess postoperative changes in hepatic and renal function in this population. METHODS: Retrospective cohort study of adults with CHD undergoing isolated heart transplant at Mayo Clinic (2003-2019). Global hepatic function was assessed using the model for end-stage liver disease excluding international normalized ratio [MELD-XI]) score; hepatic fibrosis was assessed using the fibrosis-4 (FIB-4) score and aspartate/platelet ratio index (APRI); and renal function was assessed using estimated glomerular filtration rate (GFR). All indices were measured preoperatively and postoperatively (at 6 months, 1 year, 2 years). RESULTS: Of 40 patients (age 41 ± 8 years) in the study, 35 had complete preoperative and postoperative data. There was a temporal improvement in hepatic and renal indices from preop (MELD-XI 14 ± 5, APRI 0.60 ± 0.23, FIB-4 1.44 ± 0.38, GFR 59 [44-83]) to 6 months postop (MELD-XI 12 ± 6, APRI 0.49 ± 0.17, FIB-4 1.29 ± 0.33, GFR 68 [54-96]) and 1-year postop (MELD-XI 9 ± 3, APRI 0.41 ± 0.16, FIB-4 1.12 ± 0.29, GFR 82 [69-108]), p < 0.05 for all comparisons. CONCLUSIONS: CHD patients undergoing isolated heart transplant had significant improvement in hepatic and renal function. These data suggests that selected CHD patients may do well with isolated heart transplant despite reduced hepatic and renal function, and hepatic fibrosis preoperatively. More rigorous prospective studies are required to determine the relative outcomes of isolated versus combined heart-liver transplant in this population.

Mito-targeted antioxidant prevents cardiovascular remodelling in spontaneously hypertensive rat by modulation of energy metabolism.

Hypertension induced left ventricular hypertrophy (LVH) augments the risk of cardiovascular anomalies. Mitochondrial alterations result in oxidative stress, accompanied by decrease in fatty acid oxidation, leading to the activation of the hypertrophic program. Targeted antioxidants are expected to reduce mitochondrial reactive oxygen species more effectively than general antioxidants. This study was designed to assess whether the mito-targeted antioxidant, Mito-Tempol (Mito-TEMP) is more effective than the general oxidant, Tempol (TEMP) in reduction of hypertension and hypertrophy and prevention of shift in cardiac energy metabolism. Spontaneously hypertensive rats were administered either TEMP (20 mg/kg/day) or Mito-TEMP (2 mg/kg/day) intraperitoneally for 30 days. Post treatment, animals were subjected to 2D-echocardiography. Myocardial lysates were subjected to RPLC - LTQ-Orbitrap-MS analysis. Mid-ventricular sections were probed for markers of energy metabolism and fibrosis. The beneficial effect on cardiovascular structure and function was significantly higher for Mito-TEMP. Increase in mitochondrial antioxidants and stimulation of fatty acid metabolism; with significant improvement in cardiovascular function was apparent in spontaneously hypertensive rats (SHR) treated with Mito-TEMP. The study indicates that Mito-TEMP is superior to its non- targeted isoform in preventing hypertension induced LVH, and the beneficial effects on heart are possibly mediated by reversal of metabolic remodelling.

Human gut bacterial metabolism drives Th17 activation and colitis.

Bacterial activation of T helper 17 (Th17) cells exacerbates mouse models of autoimmunity, but how human-associated bacteria impact Th17-driven disease remains elusive. We show that human gut Actinobacterium Eggerthella lenta induces intestinal Th17 activation by lifting inhibition of the Th17 transcription factor Rorγt through cell- and antigen-independent mechanisms. E. lenta is enriched in inflammatory bowel disease (IBD) patients and worsens colitis in a Rorc-dependent manner in mice. Th17 activation varies across E. lenta strains, which is attributable to the cardiac glycoside reductase 2 (Cgr2) enzyme. Cgr2 is sufficient to induce interleukin (IL)-17a, a major Th17 cytokine. cgr2+ E. lenta deplete putative steroidal glycosides in pure culture; related compounds are negatively associated with human IBD severity. Finally, leveraging the sensitivity of Cgr2 to dietary arginine, we prevented E. lenta-induced intestinal inflammation in mice. Together, these results support a role for human gut bacterial metabolism in driving Th17-dependent autoimmunity.

Prevalence and risk of progressive aortic aneurysm and dissection in adults with conotruncal anomalies.

AIMS: Conotruncal anomalies share common embryogenic defects of the outflow tracts and great arteries, which result in a predisposition to aortic aneurysms. The purpose of this study was to describe the prevalence and risk of progressive aortic aneurysms in adults with conotruncal anomalies. METHODS AND RESULTS: Retrospective study of adults with conotruncal anomalies that underwent cross-sectional imaging 2003-20. Aneurysm was defined as aortic root/mid-ascending aorta >2.1 mm/m2/>1.9 mm/m2, progressive aneurysm as increase by >2 mm, and severe aneurysm as dimension >50 mm. Of 2261 patients (38 ± 12 years; male 58%), 1167 (52%) had an aortic aneurysm, and 205 (14%) had a severe aortic aneurysm. Mean annual increase in aortic root/mid-ascending aorta was 0.3 ± 0.1 mm/0.2 ± 0.1 mm. The 3-, 5-, and 7-year cumulative incidence of the progressive aortic aneurysm was 4%, 7%, and 9%, respectively. The rate of aneurysm growth decreased with age, with no significant growth after age 40 years. There was an excellent correlation between aortic indices from cross-sectional imaging and echocardiography. Of 950 females, 184 had ≥1 pregnancy, and 81 (44%) of the 184 patients had aortic aneurysm prior to pregnancy. There was no aortic dissection or progression of the aortic aneurysm during pregnancy. Overall, there was no aortic dissection during 7984 patient-years of follow-up. CONCLUSIONS: Aortic aneurysm was common in patients with conotruncal anomalies. However, the risk of progressive aneurysm or dissection was low. Collectively, these data suggest a benign natural history and perhaps a less frequent need for cross-sectional imaging. Further studies are required to determine the optimal timing for surgical intervention in this population.

Determinants of Aerobic Capacity After Tricuspid Valve Replacement in Congenitally Corrected Transposition of Great Arteries.

Background: Systemic tricuspid regurgitation and impaired aerobic capacity are common in adults with congenitally corrected transposition of great arteries (cc-TGA), but it is unknown whether systemic tricuspid valve replacement (sTVR) is associated with improvement in aerobic capacity. Objectives: The purpose of this study was to determine whether sTVR was associated with postoperative improvement in aerobic capacity as measured by peak oxygen consumption (VO2). Methods: This is a retrospective cohort study of adults with cc-TGA and ≥moderate tricuspid regurgitation that underwent sTVR and exercise test pre- and post-sTVR (2003-2019). We selected a propensity-matched control group of patients with cc-TGA and ≥moderate tricuspid regurgitation that did not undergo sTVR between exercise tests. Improvement in aerobic capacity was calculated as the difference between baseline and follow-up exercise tests. Results: The study comprised 48 patients in each group, and both groups had similar peak VO2 at baseline. Compared to the baseline exercise test, the sTVR group had more improvement in peak VO2 (6 ± 4% vs -8 ± 3%-predicted, P = 0.001), and the factors associated with postoperative improvement in peak VO2 were baseline systolic blood pressure (<120 mm Hg), systemic right ventricular global longitudinal strain (<-16%), and preoperative peak VO2 (>60%-predicted). Conclusions: There was an improvement in aerobic capacity after sTVR in patients with cc-TGA and severe tricuspid regurgitation. The determinants of improvement in aerobic capacity were baseline systolic blood pressure, systemic right ventricular global longitudinal strain, and preoperative peak VO2. Further studies are required to determine whether strict blood pressure control and optimal timing of sTVR based on these indices would result in improved clinical outcomes in this population.

Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome.

Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used to deliver DNA to Escherichia coli within the mouse gastrointestinal (GI) tract. Delivery of a programmable exogenous CRISPR-Cas9 system enables the strain-specific depletion of fluorescently marked isogenic strains during competitive colonization and genomic deletions that encompass the target gene in mice colonized with a single strain. Multiple mechanisms allow E. coli to escape targeting, including loss of the CRISPR array or even the entire CRISPR-Cas9 system. These results provide a robust and experimentally tractable platform for microbiome editing, a foundation for the refinement of this approach to increase targeting efficiency, and a proof of concept for the extension to other phage-bacterial pairs of interest.

A Spectrum of Pulmonary Complications Occurring in End-Stage Renal Disease Patients on Maintenance Hemodialysis.

Objective To investigate the trends of end-stage renal disease (ESRD) in patients undergoing maintenance hemodialysis (MHD) and find the correlation with effects on the pulmonary system in such patients. Methodology A multicentric prospective study was conducted in the city of Solapur, India. Data were collected from 250 patients through interpersonal interrogation using a questionnaire to capture basic demographic details, the history of ESRD, and relevant respiratory symptoms like breathlessness, cough, fever, etc. related to their disease. Symptoms that are likely associated with the pulmonary system were analyzed and referred to the pulmonology department. Appropriate diagnoses were made using relevant diagnostic tools like X-rays and sputum studies. The association between various disease attributes and pulmonary diagnoses was analyzed using the chi-square (χ2) test, with a p-value of value less than or equal to 0.05 considered statistically significant. Various socio-demographic variables, existing comorbidities, occupation-related risk factors, smoking history, past or current history of any respiratory conditions, the association between the causes of ESRD, time since the first dialysis and sociodemographic factors, and frequency of pulmonary complications were the other covariates in the study. Results Our study reports that 31.6% of our patients had significant impairment in their functioning due to respiratory complaints. The prevalence of respiratory complications was 27.2%. Major contributors were pleural effusion (33.8), pneumonia (25), pulmonary edema (20.58), pleuritis (11.76), collapse (8.8), tuberculosis (5.8), fibrosis (4.4), pericardial effusion (4.4), calcification (2.9), and hydrothorax (1.47). We report one case of Urinothorax as a rare cause of hydrothorax in such patients. Overall, our analysis found a significant association between non-reporting of respiratory complaints and acute admissions to the intensive care unit (ICU) with a respiratory cause at p-value 0.0076 with a greater predilection toward the rural populations. Conclusion Our study results highlight the prevalence of pulmonary complications in ESRD patients. The occurrence of pulmonary complications, irrespective of the presence of symptoms and a greater association between non-reporting of respiratory symptoms and acute admissions to the ICU, is a hallmark to consider the importance of history and clinical vigilance during patient visits.

Western Diet and Psoriatic-Like Skin and Joint Diseases: A Potential Role for the Gut Microbiota.

Shi et al. (2021) in "Short-term Western diet intake promotes IL-23-mediated skin and joint inflammation accompanied by changes to the gut microbiota in mice" show that Western diet (WD) exacerbates an IL-23 minicircle‒mediated model of psoriasis and psoriatic arthritis, with an expansion of IL-17A‒expressing γδ T cells and shifts to the gut microbial community. WD-associated inflammation is mitigated by diet manipulation or antibiotic administration. These results suggest that dietary manipulation may be useful in the treatment of IL-23‒mediated disease, possibly through the modulation of the gut microbiota.

Methotrexate impacts conserved pathways in diverse human gut bacteria leading to decreased host immune activation.

Immunomodulatory drugs can inhibit bacterial growth, yet their mechanism of action, spectrum, and clinical relevance remain unknown. Methotrexate (MTX), a first-line rheumatoid arthritis (RA) treatment, inhibits mammalian dihydrofolate reductase (DHFR), but whether it directly impacts gut bacteria is unclear. We show that MTX broadly alters the human gut microbiota. Drug sensitivity varied across strains, but the mechanism of action against DHFR appears conserved between mammalian and bacterial cells. RA patient microbiotas were sensitive to MTX, and changes in gut bacterial taxa and gene family abundance were distinct between responders and non-responders. Transplantation of post-treatment samples into germ-free mice given an inflammatory trigger led to reduced immune activation relative to pre-treatment controls, enabling identification of MTX-modulated bacterial taxa associated with intestinal and splenic immune cells. Thus, conservation in cellular pathways across domains of life can result in broad off-target drug effects on the human gut microbiota with consequences for immune function.

Pharmacomicrobiomics in inflammatory arthritis: gut microbiome as modulator of therapeutic response.

In the past three decades, extraordinary advances have been made in the understanding of the pathogenesis of, and treatment options for, inflammatory arthritides, including rheumatoid arthritis and spondyloarthritis. The use of methotrexate and subsequently biologic therapies (such as TNF inhibitors, among others) and oral small molecules have substantially improved clinical outcomes for many patients with inflammatory arthritis; for others, however, these agents do not substantially improve their symptoms. The emerging field of pharmacomicrobiomics, which investigates the effect of variations within the human gut microbiome on drugs, has already provided important insights into these therapeutics. Pharmacomicrobiomic studies have demonstrated that human gut microorganisms and their enzymatic products can affect the bioavailability, clinical efficacy and toxicity of a wide array of drugs through direct and indirect mechanisms. This discipline promises to facilitate the advent of microbiome-based precision medicine approaches in inflammatory arthritis, including strategies for predicting response to treatment and for modulating the microbiome to improve response to therapy or reduce drug toxicity.

Column-Free Method for Isolation and Culture of C-Kit Positive Stem Cells from Atrial Explants.

Ever since the discovery of stem cells, their isolation from tissues and expansion in culture has been extensively studied due to its potential for therapeutic application. The magnetic-assisted cell sorting (MACS) method is the most widely used technique for the sorting of cells based on their cell surface markers. Though effective, the major drawbacks are high cost and the requirement for the frequent replacement of the columns. In the column-free method, the cells are sorted using the same principle of immune-magnetic isolation but does not require magnetic columns, making it cost-effective. The isolation of c-kit+ stem cells from atrial explants using column-free magnet is found to be efficient and yields homogenous population of stem cells. This method saves time and labor and is economical when working with large sample sizes.