Different modalities to manage rheumatoid arthritis: an A to Z story.

Aim: To investigate different approaches to RA treatment that might lead to greater efficacy and better safety profiles. Methods: The Search strategy was based on medical subject headings, and screening and selection were based on inclusion/exclusion criteria. Results & discussion: Early therapy is critical for disease control and loss of bodily function. The most promising outcomes came from the development of disease-modifying anti-rheumatic drugs. Different foods have anti-inflammatory and antioxidant qualities that protect against the development of rheumatoid arthritis (RA). Some dietary patterns and supplements have been shown to have potential protective benefits against RA. Conclusion: Improvement in the quality of life of RA patients requires a tailored management approach based on the current patient medical data.

Rheumatoid arthritis is a complex disease with an unclear origin that affects the joints. In this systematic review, we aimed to investigate different effective ways of treating rheumatoid arthritis. Study results indicate that rheumatoid arthritis treatment requires coordination between different healthcare teams. As much as we can, when we start disease treatment early, this will lead to a better disease cure. Different drugs showed promising results in the treatment of rheumatoid arthritis, but the most promising treatment results came from a group of medicinal agents called 'disease-modifying anti-rheumatic drugs'. Different foods have anti-inflammatory and antioxidant effect and help in protection against rheumatoid arthritis, but others, such as red meat and salt, have the opposite effect. Some dietary patterns and supplements, such as the Mediterranean Diet, vitamin D and probiotics, have been shown to have potential protective benefits against rheumatoid arthritis. Improvement in the quality of patient life requires an individualized management roadmap based on current patient medical data.

Asiatic acid rescues intestinal tissue by suppressing molecular, biochemical, and histopathological changes associated with the development of ulcerative colitis.

Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were down-regulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC.

The art of healing hearts: Mastering advanced RNA therapeutic techniques to shape the evolution of cardiovascular medicine in biomedical science.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are associated with increasing financial health burden that requires research into novel therapeutic approaches. Since the early 2000s, the availability of next-generation sequencing techniques such as microRNAs, circular RNAs, and long non-coding RNAs have been proven as potential therapeutic targets for treating various CVDs. Therapeutics based on RNAs have become a viable option for addressing the intricate molecular pathways that underlie the pathophysiology of CVDs. We provide an in-depth analysis of the state of RNA therapies in the context of CVDs, emphasizing various approaches that target the various stages of the basic dogma of molecular biology to effect temporary or long-term changes. In this review, we summarize recent methodologies used to screen for novel coding and non-coding RNA candidates with diagnostic and treatment possibilities in cardiovascular diseases. These methods include single-cell sequencing techniques, functional RNA screening, and next-generation sequencing.Lastly, we highlighted the potential of using oligonucleotide-based chemical products such as modified RNA and RNA mimics/inhibitors for the treatment of CVDs. Moreover, there will be an increasing number of potential RNA diagnostic and therapeutic for CVDs that will progress to expand for years to come.

Alkaline protease functionalized hydrothermal synthesis of novel gold nanoparticles (ALPs-AuNPs): A new entry in photocatalytic and biological applications.

Researchers are consistently investigating novel and distinctive methods and materials that are compatible for human life and environmental conditions This study aimed to synthesize gold nanoparticles (ALPs-AuNPs) using for the first time an alkaline protease (ALPs) derived from Phalaris minor seed extract. A series of physicochemical techniques were used to inquire the formation, size, shape and crystalline nature of ALPs-AuNPs. The nanoparticles' ability to degrade methylene blue (MB) through photocatalysis under visible light irradiation was assessed. The findings demonstrated that ALPs-AuNPs exhibited remarkable efficacy by destroying 100 % of MB within a mere 30-minute irradiation period. In addition, the ALPs-AuNPs demonstrated remarkable effectiveness in inhibiting the growth of gram-positive (S. aureus) and gram-negative (E. coli) bacteria. The inhibition zones examined against the two bacterial strains were 23(±0.3) mm and 19(±0.4); 13(±0.3) mm and 11(±0.5) mm under light and dark conditions respectively. The ALPs-AuNPs exhibited significant antioxidant activity by effectively scavenging 88 % of stable and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. As a result, the findings demonstrated that the environmentally friendly ALPs-AuNPs showed a strong potential for MB degradation and bacterial pathogen treatment.

Burden of routine orthopedic implant removal a single center retrospective study.

BACKGROUND: Open reduction and internal fixation represent prevalent orthopedic procedures, sparking ongoing discourse over whether to retain or remove asymptomatic implants. Achieving consensus on this matter is paramount for orthopedic surgeons. This study aims to quantify the impact of routine implant removal on patients and healthcare facilities. A retrospective analysis of implant removal cases from 2016 to 2022 at King Fahad Hospital of the University (KFHU) was conducted and subjected to statistical scrutiny. Among these cases, 44% necessitated hospitalization exceeding one day, while 56% required only a single day. Adults exhibited a 55% need for extended hospital stays, contrasting with 22.8% among the pediatric cohort. The complication rate was 6%, with all patients experiencing at least one complication. Notably, 34.1% required sick leave and 4.8% exceeded 14 d. General anesthesia was predominant (88%). Routine implant removal introduces unwarranted complications, particularly in adults, potentially prolonging hospitalization. This procedure strains hospital resources, tying up the operating room that could otherwise accommodate critical surgeries. Clearly defined institutional guidelines are imperative to regulate this practice. AIM: To measure the burden of routine implant removal on the patients and hospital. METHODS: This is a retrospective analysis study of 167 routine implant removal cases treated at KFHU, a tertiary hospital in Saudi Arabia. Data were collected in the orthopedic department at KFHU from February 2016 to August 2022, which includes routine asymptomatic implant removal cases across all age categories. Nonroutine indications such as infection, pain, implant failure, malunion, nonunion, restricted range of motion, and prominent hardware were excluded. Patients who had external fixators removed or joints replaced were also excluded. RESULTS: Between February 2016 and August 2022, 360 implants were retrieved; however, only 167 of those who met the inclusion criteria were included in this study. The remaining implants were rejected due to exclusion criteria. Among the cases, 44% required more than one day in the hospital, whereas 56% required only one day. 55% of adults required more than one day of hospitalization, while 22.8% of pediatric patients required more than one day of inpatient care. The complication rate was 6%, with each patient experiencing at least one complication. Sick leave was required in 34.1% of cases, with 4.8% requiring more than 14 d. The most common type of anesthesia used in the surgeries was general anesthesia (88%), and the mean (SD) surgery duration was 77.1 (54.7) min. CONCLUSION: Routine implant removal causes unnecessary complications, prolongs hospital stays, depletes resources and monopolizing operating rooms that could serve more critical procedures.

Okra [Abelmoschus esculentus (L.) Moench] improved blood glucose and restored histopathological alterations in splenic tissues in a rat model with streptozotocin-induced type 1 diabetes through CD8+ T cells and NF-kß expression.

Diabetes mellitus is a complex metabolic syndrome that involves dysfunction of spleen and other lymphoid organs. Medicinal plants, including okra (Abelmoschus esculentus (L.) Moench), were used widely for diabetes treatment. Scarce data are available about the potential anti-diabetic effects of okra, the histopathological alterations in splenic tissues and the mechanistic pathways underlying this association. The current research investigated the effects of okra pod extract on the biochemical parameters and expression of CD8+ T cells and nuclear factor kappa (NF-k) B and releasing proinflammatory cytokines in spleen in streptozotocin (STZ)-induced diabetic rat models. A total of 50 mature male Wister albino rats were divided into five isolated groups; the first served as control (untreated) animals, the second (DM group) diabetes induced by STZ (at a dose of 45 mg/kg body weight, administered intraperitoneally), the third group (DM + Insulin): diabetic rats administered insulin subcutaneously (10 units/kg bw/day) daily for 4 weeks, the fourth group was administrated 400 mg/kg okra extract daily for 4 weeks, and diabetic induced rats in the fifth group were administrated 400 mg/kg okra extract daily for 4 weeks. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity in Abelmoschus esculentus (L.) Moench was studied, and the content of phenolic compounds in okra pods was estimated using high-performance liquid chromatography. Diabetes induction led to decreased body weight, increased blood glucose levels. Capsular thickness was significantly increased, white pulp was widely dispersed, and mature lymphocytes in the periphery were also drastically decreased, with thick follicular arteries, necrosis, and depletion of lymphocytes in the germinal center. Red pulp revealed severe congestion and degenerative changes, deposition of hemosiderin granules and lymphocytic depletion. In addition, collagen fiber deposition was increased also in this group. The induction of diabetes exaggerated NF-kß expression and mediated downregulation of the expression of CD8+ T cells in spleen tissue. Interestingly, oral administration of okra extracts post diabetes induction could mitigate and reverse such adverse effects. Altogether, our study points out the potential benefits of okra in improving blood glucose levels and restoring histopathological alterations in splenic tissues through CD8+ T cells and NF-kß expression in a diabetic rat model.

The Management of Intussusception: A Systematic Review.

Intussusception (ISN) is a dangerous condition where a portion of the intestine slides into an adjacent area of the intestine. This telescoping motion frequently prevents liquids or food from flowing through. Developing management guidelines for ileocolic (IC) intussusception was the aim of this systematic study. Data sources were PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Scopus, and Embase databases. Our review investigated English-language articles (from 2010 to 2023) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Overall, there were 15 articles. Surveys and analyses of national databases were the most widely used methods (n=15). The search identified 561 studies; 15 were eligible for inclusion in the analysis. Further understanding of the management of intussusception may help improve evaluation and management in the future. The use of preventive antibiotics does not reduce problems following radiologic reduction. When clinically appropriate, repeated attempts at enema reduction may be made. After the enema reduction of ileocolic intussusception, patients can be safely watched in the emergency room (ER), thereby avoiding hospitalization. Success rates for laparoscopic reduction are high. When it comes to intussusception in children who are hemodynamically stable and do not have a serious illness, there is no need for pre-reduction antibiotics. Prioritizing nonoperative outpatient (OP) therapy is recommended as the primary approach, with the utilization of minimally invasive procedures to avoid the necessity for laparotomy. The management of colonic intussusception involves complete removal in one piece, while enteric intussusception can be addressed through reduction followed by resection. A targeted approach is recommended, recognizing the intermediate forms of intussusception that may exist between the colonic and enteric types. It is essential to note that the prevailing treatment for adult intussusception remains to be surgical intervention.

Prevalence and impact of long COVID-19 among patients with diabetes and cardiovascular diseases in Bangladesh.

Introduction: Co-prevalence of long-COVID-19, cardiovascular diseases and diabetes is one of the major health challenges of the pandemic worldwide. Studies on long-COVID-19 and associated health outcomes are absent in Bangladesh. The main aim of this study was to determine the prevalence and impact of long-COVID-19 on preexisting diabetes and cardiovascular diseases (CVD) on health outcomes among patients in Bangladesh. Methods: We collected data from 3,250 participants in Bangladesh, retrospectively. Multivariable logistic regression model was used to determine the odds ratio between independent and dependent variables. Kaplan-Meier survival curve was used to determine the cumulative survival. Results: COVID-19 was detected among 73.4% (2,385 of 3,250) participants. Acute long-COVID-19 was detected among 28.4% (678 of 2,385) and chronic long-COVID-19 among 71.6% (1,707 of 2,385) patients. CVD and diabetes were found among 32%, and 24% patients, respectively. Mortality rate was 18% (585 of 3,250) among the participants. Co-prevalence of CVD, diabetes and COVID-19 was involved in majority of fatality (95%). Fever (97%), dry cough (87%) and loss of taste and smell (85%) were the most prevalent symptoms. Patients with co-prevalence of CVD, diabetes and COVID-19 had higher risk of fatality (OR: 3.65, 95% CI, 2.79-4.24). Co-prevalence of CVD, diabetes and chronic long-COVID-19 were detected among 11.9% patients. Discussion: Risk of hospitalization and fatality reduced significantly among the vaccinated. This is one of the early studies on long-COVID-19 in Bangladesh.

Comparative Evaluation of Salivary Parameters in Tobacco Substance Abusers.

BACKGROUND: Tobacco use by youth is ever-demanding, and it is increasingly distributed not only in India but also globally. Saliva is a complex oral bio-fluid, freely available, performing absolute tasks for maintaining oral health and homeostasis. It contains a plethora of significant constituents such as proline-rich proteins (PRPs), immunoglobulins, IgA, enzymes lysozyme, lactoferrin, peroxidases, amylase, etc. The basic ecological balance of the oral cavity is stabilized via salivary clearance by reduced aggregation and adherence of microorganisms by direct microbial activity. This balance of oral activity is also done by indirect mechanisms by immunological as well as non-immunological means and also by effectively regulating salivary pH flow rate. This institutional observational study was planned to assess and compare salivary parameters (pH, salivary flow rate), total proteins, α-amylase, calcium, phosphate, and IgA, of unstimulated whole saliva of both tobacco abusers and tobacco non-users. METHODS: The Study consisted of 270 participants (Tobacco habit) group, n = 135 and Control (Healthy) group, n = 135 and were in the age range of 20-50 years. They were assessed for oral health status, followed by the analysis of salivary pH, flow rate, total proteins, amylase, calcium, phosphates, and IgA of unstimulated whole saliva. RESULTS: Comparative evaluation of salivary parameters among groups found that varying tobacco abusers had increased salivary amylase, protein levels, and phosphate whereas decreased salivary pH, flow rate, IgA, and in the whole unstimulated saliva samples than those of non-tobacco users. This difference among groups was statistically significant. (p < 0.05), and calcium levels were not altered significantly. CONCLUSIONS: This study concludes that salivary parameters are altered in tobacco abusers when compared to those of non-abusers, and it was more significant in smokeless tobacco abusers than in any other form of tobacco abuse.

Evaluating the Efficacy of Platelet-Rich Fibrin Matrix versus Subepithelial Connective Tissue Grafts in Dental Root Coverage: A Comparative Study Using Modified Ruben's Technique.

BACKGROUND Dental root coverage, crucial in managing gingival recessions, traditionally utilizes subepithelial connective tissue grafts. However, this approach has limitations such as donor site morbidity and graft availability. Recent studies have introduced platelet-rich fibrin (PRF) as an alternative, leveraging its regenerative potential and growth factors. Despite the promise, comparative assessments between PRF and conventional grafts remain limited. This research probes whether PRF, when used beneath a modified Ruben's mixed flap, could provide comparable or superior dental root coverage than a subepithelial connective tissue graft. MATERIAL AND METHODS We enrolled 30 patients exhibiting Miller's class I and II recession in this comparative case series. Patients were randomly assigned to receive either a connective tissue graft (15 patients) or a PRF matrix (15 patients), both covered by a modified Ruben's mixed flap. RESULTS Clinical parameters, including full mouth plaque scores, bleeding scores, probing sulcus depth, clinical attachment level, gingival position assessment, width, and thickness of attached gingiva, were assessed in both the control and test groups at baseline, 6 months, and 12 months post-surgery. Significant differences were observed at all intervals.At the 12-month mark, the control group (connective tissue graft) achieved 91% complete root coverage, while the test group (PRF matrix) achieved 86%. However, this difference was not statistically significant. CONCLUSIONS The study outcomes suggest comparable gains in root coverage and attached gingiva between the connective tissue graft and PRF matrix groups. Thus, the results support our hypothesis that a subepithelial PRF matrix can serve as a viable alternative to a subepithelial connective tissue graft for treating dental root coverage.

Molecular epidemiology, transmission and clinical features of 2022-mpox outbreak: A systematic review.

Background and Aims: The 2022-mpox outbreak has spread worldwide in a short time. Integrated knowledge of the epidemiology, clinical characteristics, and transmission of mpox are limited. This systematic review of peer-reviewed articles and gray literature was conducted to shed light on the epidemiology, clinical features, and transmission of 2022-mpox outbreak. Methods: We identified 45 peer-reviewed manuscripts for data analysis. The standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration were followed for conducting the study. Results: The case number of mpox has increased about 100 times worldwide. About 99% of the cases in 2022 outbreak was from non-endemic regions. Men (70%-98% cases) were mostly infected with homosexual and bisexual behavior (30%-60%). The ages of the infected people ranged between 30 and 40 years. The presence of HIV and sexually transmitted infections among 30%-60% of cases were reported. Human-to-human transmission via direct contact and different body fluids were involved in the majority of the cases (90%-100%). Lesions in genitals, perianal, and anogenital areas were more prevalent. Unusually, pharyngitis (15%-40%) and proctitis (20%-40%) were more common during 2022 outbreak than pre-2022 outbreaks. Brincidofovir is approved for the treatment of smallpox by FDA (USA). Two vaccines, including JYNNEOSTM and ACAM2000®, are approved and used for pre- and post-prophylaxis in cases. About 100% of the cases in non-endemic regions were associated with isolates of IIb clade with a divergence of 0.0018-0.0035. Isolates from B.1 lineage were the most predominant followed by B.1.2 and B.1.10. Conclusion: This study will add integrated knowledge of the epidemiology, clinical features, and transmission of mpox.

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study.

Background: Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes. Objective: This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how ß-cells of the pancreas in diabetic rats respond to MT administration. Materials and methods: Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively. Results: MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the ß-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic ß-cells; its antioxidant effect also reduced hepatocyte injury. Conclusion: Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic ß-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes.

Efficacy of laser in re-osseointegration of dental implants-a systematic review.

Despite their high success rates, peri-implantitis can affect the stability and function of dental implants. Various treatment modalities have been investigated for the treatment of peri-implantitis to achieve re-osseointegration. An electronic literature search was performed supplemented by a manual search to identify studies published until January 2022. Articles that evaluated re-osseointegration in peri-implantitis sites in animal models following laser therapy or antimicrobial photodynamic therapy (aPDT) were included. Case reports, case series, systematic reviews, and letters to the editor were excluded. Risk of bias and GRADE assessment were followed to evaluate the quality of the evidence. Six studies out of 26 articles identified on electronic search were included in this review. The studies included animal studies conducted on canine models. Four out of six studies reported a higher degree of re-osseointegration following treatment of implants with laser therapy. The findings suggest that laser decontamination shows potential in enhancing re-osseointegration, particularly with the Er: YAG laser, which effectively decontaminated implant surfaces. However, conflicting outcomes and limitations in the evidence quality warrant caution in drawing definitive conclusions. Based on the limited available evidence, laser therapy may show a higher degree of re-osseointegration of implants than mechanical debridement.

Eleven Crucial Pesticides Appear to Regulate Key Genes That Link MPTP Mechanism to Cause Parkinson's Disease through the Selective Degeneration of Dopamine Neurons.

Pesticides kill neurons, but the mechanism leading to selective dopaminergic loss in Parkinson's disease (PD) is unknown. Understanding the pesticide's effect on dopaminergic neurons (DA) can help to screen and treat PD. The critical uptake of pesticides by the membrane receptors at DA is hypothesized to activate a signaling cascade and accelerate degeneration. Using MPTP as a reference, we demonstrate the mechanisms of eleven crucial pesticides through molecular docking, protein networks, regulatory pathways, and prioritization of key pesticide-regulating proteins. Participants were recruited and grouped into control and PD based on clinical characteristics as well as pesticide traces in their blood plasma. Then, qPCR was used to measure pesticide-associated gene expression in peripheral blood mononuclear cells between groups. As a result of molecular docking, all eleven pesticides and the MPTP showed high binding efficiency against 274 membrane receptor proteins of DA. Further, the protein interaction networks showed activation of multiple signaling cascades through these receptors. Subsequent analysis revealed 31 biological pathways shared by all 11pesticides and MPTP that were overrepresented by 46 crucial proteins. Among these, CTNNB1, NDUFS6, and CAV1 were prioritized to show a significant change in gene expression in pesticide-exposed PD which guides toward therapy.

Effects of Bacterial Metabolites on the Wnt4 Protein in Dental-Pulp-Stem-Cells-Based Endodontic Pulpitis Treatment.

Porphyromonas gingivalis is associated with endodontic pulpitis, causing damage to the dental pulp, leading to severe pain and a decline in quality of life. Regenerative pulp treatments using dental pulp stem cells (DPSCs) can be hindered by interactions between DPSCs and the infecting bacteria. The protein WNT family member 4 (Wnt4) plays a critical role in the differentiation of DPSCs and the regeneration of odontogenic tissue. However, the specific influence of P. gingivalis on Wnt4 remains unclear. In this study, we employed a computational approach to investigate the underlying mechanisms through which P. gingivalis-produced metabolites inhibit the Wnt4 protein, thereby diminishing the regenerative potential and therapeutic efficacy of odontogenic tissue. Among the metabolites examined, C29H46N7O18P3S-4 exhibited the strongest inhibitory effect on the Wnt4 protein, as evidenced by the lowest binding energy score of -6782 kcal/mol. Molecular dynamic simulation trajectories revealed that the binding of C29H46N7O18P3S-4 significantly altered the structural dynamics and stability of the Wnt4 protein. These alterations in protein trajectories may have implications for the molecular function of Wnt4 and its associated pathways. Overall, our findings shed light on the inhibitory impact of P. gingivalis-produced metabolites on the Wnt4 protein. Further in vitro, in vivo, and clinical studies are necessary to validate and expand upon our findings.

Virtual screening, molecular dynamics and density functional theory on pain inhibitors against TRPV1 associating inflammatory conditions.

Transient receptor potential vanilloid 1 protein (TRPV1) is expressed widely in skin and sensory neurons that contribute to pain/heat sensation in the human system. TRPV1 gene polymorphisms are susceptible to multiple diseases and it is considered a therapeutic target for various inflammatory conditions. Among the TRPV1 variants, rs8065080 (1911 A > G) plays a vital role in painful osteoarthritis and migraine. The presence of rs8065080 polymorphism may render drug efficacy. This study aimed to identify better antagonists against wild-type and variant TRPV1 that may help in the relief of pain/inflammation. We constructed suitable TRPV1 protein structures for wild-type and rs8065080 variant through a homology modelling approach. A total of 3363 anti-inflammatory compounds with high chemical diversity and good drug-like properties were collected and screened against the generated structures. Molecular docking showed that nobilamide B had the highest binding affinity (-5.83 kcal/mol) towards the wild-type. Whereas, isoquinoline analogue displayed highest binding potency with the variant TRPV1 (-11.65 kcal/mol). Besides those, C18H15F3N4O showed affinity towards both wild-type (-5.53 kcal/mol) and variant TRPV1 (-9.75 kcal/mol). Then, molecular dynamic simulation revealed stable conformation in wild-type and variant TRPV1 upon binding of nobilmaide B, isoquinoline analogue and C18H15F3N4O. Additionally, density functional theory (DFT) using B3LYP hybrid function showed high chemical reactiveness of nobilamie B, isoquinoline analogue and C18H15F3N4O. Overall, our systematic investigations provide, C18H15F3N4O could be a potential analgesic inhibiting both wild-type and variant TRPV1 against inflammatory conditions.

High prevalence of norovirus GII.4 Sydney among children with acute gastroenteritis in Bangladesh, 2018-2021.

BACKGROUND: Active molecular surveillance and rapid diagnosis method to track an outbreak of norovirus in Bangladesh is lacking. This study aims to determine the genotypic diversity, molecular epidemiology and evaluate a rapid diagnosis method. METHODS: A total of 404 fecal specimens were collected from children aged below 60 months from January 2018 to December 2021. All samples were analyzed by reverse transcriptase polymerase chain reaction molecular sequencing of partial VP1 nucleotide. Immunochromatography kit (IC, IP Rota/Noro) was evaluated against reference test method. RESULTS: We found norovirus in 6.7 % (27 of 404) fecal specimens. A wide diversity of norovirus genotype including GII.3, GII.4, GII.5, GII.6, GII.7, and GII.9 were detected. Norovirus strain GII.4 Sydney-2012 was the most predominant (74 %, 20 of 27) followed by GII.7 (7.4 %), GII.9 (7.4 %), GII.3 (3.7 %), GII.5 (3.7 %) and GII.6 (3.7 %), respectively. Co-infection of rotavirus and norovirus (19 [4.7 %] of 404) was the most prevalent. We found higher odds of prolonged health impact [OR 1.93 (95 % CI 0.87-3.12) (p = .001)] among patients with co-infection. The incidence of norovirus was significant among the children below 24 months (p = 0.001). Significant relation of temperature with the cases of norovirus was detected (p = 0.001). The IC kit provided high specificity (99.3 %) and sensitivity (100 %) for the detection of norovirus. CONCLUSIONS: This study will provide an integrated insight on the genotypic diversity and rapid identification method of norovirus in Bangladesh.

Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis.

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Dynamics of TUBB protein with five majorly occurring natural variants: a risk of cortical dysplasia.

Beta-tubulin (TUBB) protein is one of the components of the microtubule cytoskeleton that plays a critical role in the central nervous system. Genetic variants of TUBB cause cortical dysplasia, a developmental brain defect implicated in axonal guidance and the neuron migration. In this study, we assess pathogenic variants (Q15K, Y222F, M299V, V353I, and E401K) of TUBB protein and compared with non-pathogenic variant G235S to determine their impact on protein dynamic to cause cortical dysplasia. Among the analyzed variants, Q15K, Y222F, M299V, and E401K were noticed to have deleterious effect. Then, variant structures were modeled and their affinity with their known cofactor Guanosine-5'-triphosphate (GTP) was assessed which showed diverse binding energies ranged between (-7.436 to -6.950 kcal/mol) for the variants compared to wild-type (-7.428 kcal/mol). Finally, the molecular dynamics simulation of each variant was investigated which showed difference in trajectory between the pathogenic and non-pathogenic variant. Our analysis suggests change in amino acid residue of TUBB structure has notably affects the protein flexibility and their interactions with known cofactor. Overall, our findings provide insight on the relationship between TUBB variants and their structural dynamics that may cause diverse effects leading to cortical dysplasia.

Phage engineering and phage-assisted CRISPR-Cas delivery to combat multidrug-resistant pathogens.

Antibiotic resistance ranks among the top threats to humanity. Due to the frequent use of antibiotics, society is facing a high prevalence of multidrug resistant pathogens, which have managed to evolve mechanisms that help them evade the last line of therapeutics. An alternative to antibiotics could involve the use of bacteriophages (phages), which are the natural predators of bacterial cells. In earlier times, phages were implemented as therapeutic agents for a century but were mainly replaced with antibiotics, and considering the menace of antimicrobial resistance, it might again become of interest due to the increasing threat of antibiotic resistance among pathogens. The current understanding of phage biology and clustered regularly interspaced short palindromic repeats (CRISPR) assisted phage genome engineering techniques have facilitated to generate phage variants with unique therapeutic values. In this review, we briefly explain strategies to engineer bacteriophages. Next, we highlight the literature supporting CRISPR-Cas9-assisted phage engineering for effective and more specific targeting of bacterial pathogens. Lastly, we discuss techniques that either help to increase the fitness, specificity, or lytic ability of bacteriophages to control an infection.