A besyian regularisation neural network approach for hepatitis B virus spread prediction and immune system therapy model.

The primary aim of the article is to analyze the response of the human immune system when it encounters the hepatitis B virus. This is done using a mathematical system of differential equations. The differential equation system has six components, likely representing various aspects of the immune response or virus dynamics. A Bayesian regularization neural network has been presented in the process of training. These networks are employed to find solutions for different categories or scenarios related to hepatitis B infection. The Adams method is used to generate reference data sets. The back-propagated artificial neural network, based on Bayesian regularization, is trained and validated using the generated data. The data is divided into three sets: 90% for training and 5% each for testing and validation. The correctness and effectiveness of the proposed neural network model have been assessed using various evaluation metrics. The metrics have been used in this study are Mean Square Error (MSE), histogram errors, and regression plots. These measures provide support to the neural network to approximate the immune response to the hepatitis B virus.

Biogenic synthesis of AgNPs via polyherbal formulation: Mechanistic neutralization and toxicological impact on acetylcholinesterase from Bungarus sindanus venom.

This study aims to examine the biogenic production, characterization, and anti-acetylcholinesterase (AAChE) properties of polyherbal formulation PHF-extract-synthesized silver nanoparticles (PHF-AgNPs). The Elapidae snake Bungarus sindanus has extremely dangerous venom for humans and contains a high amount of AChE (acetylcholinesterase). Inhibiting AChE leads to acetylcholine buildup, affecting neurotransmission. The study tested silver nanoparticles as AChE inhibitors using kinetics. Their production was confirmed through ultraviolet (UV) spectrometry at 425 nm (SPR peak of 1.94), and stabilizing functional groups were identified via Fourier transform infrared spectroscopy (FT-IR). The average length of 20 nm was confirmed by analyzing the scanning electron microscopy (SEM) data. Energy-dispersive X-ray spectroscopy (EDX) identified silver as the primary component of PHF-AgNPs (26%). Statistical analysis showed that the activity of AChE in krait venom decreased by up to 45% and 37% at a given dose of ACh (0.5 mM) by PHF and AgNPs, respectively. Utilizing the Lineweaver-Burk plot for kinetic analysis, a competitive type of inhibition is found. RESEARCH HIGHLIGHTS: Successfully synthesized PHF-extract-induced silver nanoparticles (PHF-AgNPs) demonstrated through UV spectrometry and characterized as crystalline with an average size of 45 nm by X-ray diffraction. PHF-AgNPs effectively inhibited acetylcholinesterase (AChE), an enzyme critical in neurotransmission, reducing its activity in krait venom by up to 45% at certain concentrations. Kinetic analysis revealed that the inhibition mechanism of AChE by PHF-AgNPs is competitive, offering potential for therapeutic applications in neurologically related conditions.

Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys.

MicroRNAs (miRNAs) play important roles in the regulation of cellular function and fate via post-transcriptional regulation of gene expression. Although several miRNAs are associated with physiological processes and kidney diseases, not much is known about changes in miRNAs in aging kidneys. We previously demonstrated that sodium hydrogen exchanger 1 (NHERF1) expression regulates cellular responses to cisplatin, age-dependent salt-sensitive hypertension, and sodium-phosphate cotransporter trafficking. However, the mechanisms driving these regulatory effects of NHERF1 on cellular processes are unknown. Here, we hypothesize that dysregulation of miRNA-mediated gene regulatory networks that induce fibrosis and cytokines may depend on NHERF1 expression. To address this hypothesis, we compared miRNA expression in kidneys from both male and female old (12-18-month-old) and young (4-7-month-old) wild-type (WT) and NHERF1 knockout (NHERF1-/-) mice. Our results identified that miRNAs significantly decreased in NHERF1-/- mice included miR-669m, miR-590-3p, miR-153, miR-673-3p, and miR-127. Only miR-702 significantly decreased in aged WT mice, while miR-678 decreased in both WT and NHERF1-/- old versus young mice. miR-153 was shown to downregulate transcription factors NFATc2 and NFATc3 which regulate the transcription of several cytokines. Immunohistochemistry and western blotting revealed a significant increase in nuclear NFATc2 and NFATc3 in old NHERF1-/- mice compared to old WT mice. Our data further show that expression of the cytokines IL-1ß, IL-6, IL-17A, MCP1, and TNF-α significantly increased in the old NHERF1-/- mice compared to the WT mice. We conclude that loss of NHERF1 expression induces cytokine expression in the kidney through interactive regulation between miR-153 and NFATc2/NFATc3 expression.

Ovarian Insufficiency in Adolescent Females with Transfusion-Dependent ß-Thalassemia: Pituitary versus Ovarian Iron Overload.

INTRODUCTION: Females with transfusion-dependent ß-thalassemia (TDT) display menstrual irregularities and subfertility at certain points in their lives, even if well-chelated, representing a significant physical and psychological burden. Little is known about the effects of pituitary and ovarian iron contents on ovarian reserve and function. Hence, this study aimed to assess ovarian reserve and pituitary-gonadal axis function in adolescent females with TDT and correlate them with pituitary and ovarian volume, pituitary iron load, and serum ferritin. METHODS: Fifty adolescent females with TDT were compared to 50 age-matched healthy females. Age of diagnosis of TDT, transfusion index, type of chelation therapy, age at menarche, and Tanner breast stage were assessed. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), and ferritin were measured. Magnetic resonance imaging (MRI) pituitary iron content R2* and T2* were measured, and 3-D transabdominal ovarian ultrasound performed. RESULTS: The mean age of the studied females with TDT was 14.54 ± 2.24 years. Ovarian insufficiency was found in 20 of them (40%). Compared to controls, adolescent females with TDT had significantly delayed age of menarche, AMH, FSH, LH, antral follicle count (AFC), and ovarian volume. Upon comparing those with ovarian insufficiency and those without, adolescents with TDT having ovarian insufficiency had significantly higher serum ferritin and pituitary MRI-R2* than those without insufficiency. Multivariate-logistic regression showed that pituitary MRI-R2* was the most significant independent variable associated with ovarian insufficiency among adolescent females with TDT. CONCLUSION: Adolescent females with TDT have decreased ovarian reserve, AFC, and gonadotropins that are correlated with serum ferritin, pituitary iron load, and ovarian volume. Hence, regular ovarian reserve assessment should be implemented as a part of endocrinological follow-up of females with TDT advising procedures to preserve fertility to those who are likely to have ovarian insufficiency.

Synthesis and Biological Evaluation of Novel Imidazole Derivatives as Antimicrobial Agents.

Imidazole derivatives are considered potential chemical compounds that could be therapeutically effective against several harmful pathogenic microbes. The chemical structure of imidazole, with a five-membered heterocycle, three carbon atoms, and two double bonds, tends to show antibacterial activities. In the present study, novel imidazole derivatives were designed and synthesized to be evaluated as antimicrobial agents owing to the low number of attempts to discover new antimicrobial agents and the emerging cases of antimicrobial resistance. Two imidazole compounds were prepared and evaluated as promising candidates regarding in vitro cytotoxicity against human skin fibroblast cells and antimicrobial activity against several bacterial strains. The synthesized imidazole derivatives were chemically identified using nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR). The results demonstrated a relatively high cell viability of one of the imidazole derivatives, i.e., HL2, upon 24 and 48 h cell exposure. Both derivatives were able to inhibit the growth of the tested bacterial strains. This study provides valuable insight into the potential application of imidazole derivatives for treating microbial infections; however, further in vitro and in vivo studies are required to confirm their safety and effectiveness.

Correction: Amin et al. Hippocampal and Cerebellar Changes in Acute Restraint Stress and the Impact of Pretreatment with Ceftriaxone. Brain Sci. 2020, 10, 193.

In the original publication [...].

Developing and Validating Entrustable Professional Activities (EPAs) for Rheumatology Fellowship Training Programs in Saudi Arabia: A Delphi Study.

Background: Entrustable professional activities (EPAs) define the core tasks that a graduating rheumatologist needs to perform independently in practice. The objective of this study was to develop and validate EPAs for rheumatology fellowship training programs in Saudi Arabia. Methods: Experts met to develop an initial set of potential end-of-training EPAs by conducting a comprehensive literature review of EPAs and studying the Saudi rheumatology fellowship curriculum. Then, to validate the EPAs, we conducted two rounds of the modified Delphi technique among rheumatology experts in Saudi Arabia. A response rate of 80% was considered and the minimum number of experts needed to be 25 to 30. Descriptive statistics were utilized to describe participants' demographic characteristics and group responses to each statement in all rounds. The experts were asked to rate the relevancy of each EPA using a 5-point Likert scale in both Delphi rounds. Results: In the preliminary phase, four rheumatologists developed an initial set of 36 core EPAs for rheumatology training program in Saudi Arabia. For the two-rounds Delphi techniques, 32 experts were invited to complete the study. The response rate of the first and second round were, 78.12% (25) and 93.75% (30), respectively. The first-round Delphi resulted in a robust consensus on 31 EPAs for rheumatology training. Five EPAs were excluded, and one new EPA was proposed. In the subsequent round, all 32 EPAs achieved strong consensus. The eliminated EPAs likely fell short in one or more of the following areas: relevance to rheumatology practice in Saudi Arabia, overlapping with other EPAs, or practical challenges in the implementation. Conclusion: We have developed and validated a core set of EPAs for rheumatology fellowship training programs in Saudi Arabia. Mapping and identifying milestones for these EPAs are essential steps to follow to enhance workplace curriculum development.

Financial Toxicity Screening Preferences in Patients With Breast Cancer.

PURPOSE: Financial toxicity is an important issue in cancer that affects quality of life and treatment adherence. Screening can identify patients at risk but consensus on appropriate timing or methods is lacking. METHODS: We sent an anonymous survey to e-mail subscribers of a nationwide breast cancer-specific philanthropic organization in July 2023 asking about financial toxicity screening preferences. Frequencies, percentages, and medians were calculated for categorical and continuous variables. RESULTS: Of 5,774 potential participants, 738 respondents with a confirmed cancer diagnosis participated (12.7% response rate). Participants were 93% female (n = 690), had a median age of 50 years (IQR, 44-57), were 57% non-Hispanic White (n = 418), 20% Black/African-American (n = 149), 9.2% Hispanic (n = 68). 93% confirmed a breast cancer diagnosis (n = 689), and 54% were currently undergoing treatment (n = 400). Most indicated not being asked about financial stressors by (58%, n = 425) and not receiving assistance from their care team (68%, n = 498). Most preferred for providers to reach out regarding financial needs (83%, n = 615). Most wished for these discussions to take place early (when first diagnosed [45%, n = 334] or when treatment selected [37%, n = 275]) and to be asked frequently (each appointment [42%, n = 312] or once per month [36%, n = 268]). Participants felt most comfortable discussing financial needs with a social worker or patient/financial navigator (92%, n = 679), in person (75%, n = 553), or via telephone (65%, n = 479). CONCLUSION: Patients in this sample primarily consisting of women with breast cancer desired financial screening to occur early, often, and to be initiated by their providers. Patient preferences can inform optimal implementation of financial toxicity screening practices. Continued work refining best practices for financial toxicity screening should incorporate these patient preferences.

Development of two recombinant vaccines against Clostridioides difficile infection and immunogenicity in pregnant sows and neonatal piglets.

INTRODUCTION: Clostridioides difficile is the main cause of antibiotic-associated diarrhea in humans and is a major enteropathogen in several animal species. In newborn piglets, colonic lesions caused by C. difficile A and B toxins (TcdA and TcdB, respectively) cause diarrhea and significant production losses. OBJECTIVE: The present study aimed to develop two recombinant vaccines from immunogenic C-terminal fragments of TcdA and TcdB and evaluate the immune response in rabbits and in breeding sows. Two vaccines were produced: bivalent (rAB), consisting of recombinant fragments of TcdA and TcdB, and chimeric (rQAB), corresponding to the synthesis of the same fragments in a single protein. Groups of rabbits were inoculated with 10 or 50 µg of proteins adjuvanted with aluminum or 0.85 % sterile saline in a final volume of 1 mL/dose. Anti-TcdA and anti-TcdB IgG antibodies were detected in rabbits and sows immunized with both rAB and rQAB vaccines by ELISA. The vaccinated sows were inoculated intramuscularly with 20 µg/dose using a prime-boost approach. RESULTS: Different antibody titers (p ≤ 0.05) were observed among the vaccinated groups of sows (rAB and rQAB) and control. Additionally, newborn piglets from vaccinated sows were also positive for anti-TcdA and anti-TcdB IgGs, in contrast to control piglets (p ≤ 0.05). Immunization of sows with the rQAB vaccine conferred higher anti-TcdA and anti-TcdB responses in piglets, suggesting the superiority of this compound over rAB. CONCLUSION: The synthesized recombinant proteins were capable of inducing antibody titers against C. difficile toxins A and B in sows, and were passively transferred to piglets through colostrum.

Exocyclic and Linker Editing of Lys63-linked Ubiquitin Chains Modulators Specifically Inhibits Non-homologous End-joining Repair.

Despite the great advances in discovering cyclic peptides against protein targets, their reduced aqueous solubility, cell permeability, and activity of the cyclic peptide restrict its utilization in advanced biological research and therapeutic applications. Here we report on a novel approach of structural alternation of the exocyclic and linker parts that led to a new derivative with significantly improved cell activity allowing us to dissect its mode of action in detail. We have identified an effective cyclic peptide (CP7) that induces approximately a 9-fold increase in DNA damage accumulation and a remarkable increase in apoptotic cancer cell death compared to the reported molecule. Notably, treating cells with CP7 leads to a dramatic decrease in the efficiency of non-homologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs), which is accompanied by an increase in homologous recombination (HR) repair. Interestingly, treating BRCA1-deficient cells with CP7 restores HR integrity, which is accompanied by increased resistance to CP7. Additionally, CP7 treatment increases the sensitivity of cancer cells to ionizing radiation. Collectively, our findings demonstrate that CP7 is a selective inhibitor of NHEJ, offering a potential strategy to enhance the effectiveness of radiation therapy.

Validity of a single-item indicator of treatment side effect bother in patients with head and neck cancer.

PURPOSE: Patients with head/neck squamous cell carcinomas (HNSCC) experience significant tumor- and treatment-related side effects. No efficient summary measure capturing the totality of side effect burden currently exists. We examined associations between a single patient-reported outcome (PRO) item evaluating side effect bother (FACT GP5, "I am bothered by side effects of treatment") with overall side effects in HNSCC. METHODS: We performed a retrospective secondary analysis of development of the Functional Assessment of Cancer Therapy (FACT) Head/Neck Symptom Index (FHNSI-10), which included completing FACT-HN (including Head/Neck Cancer Subscale (HNCS) and Trial Outcome Index (TOI)) and the pain intensity numeric rating scale (NRS). We calculated Spearman's correlations between GP5 and these measures of patient-reported global health, head/neck side effects, and pain intensity NRS. A correlation of > 0.4 was considered sufficient evidence of association. RESULTS: Ninety-seven patients completed baseline and 85 completed 3-month follow-up surveys. GP5 was highly correlated with FACT-HN total score (baseline r = 0.66, 3 months r = 0.67) and FHNSI-10 (baseline r = 0.63, 3 months r = 0.65). GP5 correlated with multiple FACT-HN subscales including FACT-G, physical well-being, functional well-being, HNCS, and TOI (range baseline r = 0.53-0.77, range 3 months r = 0.49-0.77). Worsening GP5 score was associated with worsening overall HNCS (p = 0.002), worsening FHNSI-10 score (p < 0.001), and worsening mean pain intensity (p < 0.001). CONCLUSION: GP5 exhibited validity within HNSCC, exhibiting substantial correlations with a number of HNSCC-related PRO measures including FACT-HN and FHNSI-10. Worsening GP5 was associated with worsening HNCS, FHNSI summary score, and pain intensity. GP5 has promise as a summary indicator of symptom and side effect bother in HNSCC.

Theoretical framework and inference for fitting extreme data through the modified Weibull distribution in a first-failure censored progressive approach.

The importance of biomedical physical data is underscored by its crucial role in advancing our comprehension of human health, unraveling the mechanisms underlying diseases, and facilitating the development of innovative medical treatments and interventions. This data serves as a fundamental resource, empowering researchers, healthcare professionals, and scientists to make informed decisions, pioneer research, and ultimately enhance global healthcare quality and individual well-being. It forms a cornerstone in the ongoing pursuit of medical progress and improved healthcare outcomes. This article aims to tackle challenges in estimating unknown parameters and reliability measures related to the modified Weibull distribution when applied to censored progressive biomedical data from the initial failure occurrence. In this context, the article proposes both classical and Bayesian techniques to derive estimates for unknown parameters, survival, and failure rate functions. Bayesian estimates are computed considering both asymmetric and symmetric loss functions. The Markov chain Monte Carlo method is employed to obtain these Bayesian estimates and their corresponding highest posterior density credible intervals. Due to the inherent complexity of these estimators, which cannot be theoretically compared, a simulation study is conducted to evaluate the performance of various estimation procedures. Additionally, a range of optimization criteria is utilized to identify the most effective progressive control strategies. Lastly, the article presents a medical application to illustrate the effectiveness of the proposed estimators. Numerical findings indicate that Bayesian estimates outperform other estimation methods by achieving minimal root mean square errors and narrower interval lengths.

Physical Activity Volume, Intensity, and Mortality: Harmonized Meta-Analysis of Prospective Cohort Studies.

INTRODUCTION: It is unclear whether moderate-to-vigorous physical activity (MVPA) is associated with a lower mortality risk, over and above its contribution to total physical activity volume. METHODS: 46,682 adults (mean age: 64 years) were included in a meta-analysis of nine prospective cohort studies. Each cohort generated tertiles of accelerometry-measured physical activity volume and volume-adjusted MVPA. Hazard ratios (HR, with 95% confidence intervals) for mortality were estimated separately and in joint models combining volume and MVPA. Data was collected between 2001 and 2019 and analyzed in 2023. RESULTS: During a mean follow-up of 9 years, 4,666 deaths were recorded. Higher physical activity volume, and a greater contribution from volume-adjusted MVPA, were each associated with lower mortality hazard in multivariable-adjusted models. Compared to the least active tertile, higher physical activity volume was associated with a lower mortality (HRs: 0.62; 0.58, 0.67 and 0.50; 0.42, 0.60 for ascending tertiles). Similarly, a greater contribution from MVPA was associated with a lower mortality (HRs: 0.94; 0.85, 1.04 and 0.88; 0.79, 0.98). In joint analysis, a lower mortality from higher volume-adjusted MVPA was only observed for the middle tertile of physical activity volume. CONCLUSIONS: The total volume of physical activity was associated with a lower risk of mortality to a greater extent than the contribution of MVPA to physical activity volume. Integrating any intensity of physical activity into daily life may lower mortality risk in middle-aged and older adults, with a small added benefit if the same amount of activity is performed with a higher intensity.

Dietary trajectories over 21 years and frailty in Norwegian older adults: the Tromsø Study 1994-2016.

PURPOSE: To investigate the association between five dietary trajectories over 21 years and frailty in Norwegian older adults. METHODS: This study used data from three surveys of the Tromsø Study. Diet was measured using food frequency questionnaires at baseline (Tromsø4, 1994-95), after 7 years (Tromsø5, 2001) and at the end of follow-up (Tromsø7, 2015-16). Survey-specific diet scores were constructed based on the Nordic Nutrition Recommendations 2023 and group-based trajectory modelling was used to derive dietary trajectories. At follow-up, frailty was assessed with a 41-item frailty index. Linear regression analysis was performed to assess the associations between dietary trajectories and frailty, adjusted for baseline variables. RESULTS: Among the 715 participants, 55% were women, with an average age of 54 years at baseline and 74 years at follow-up. The dietary trajectories 'moderately healthy' and 'healthy increase' were associated with a lower frailty index score at follow-up (ß = -0.02, 95% confidence interval (CI) = -0.04, -0.002, ß = -0.03, 95% CI = -0.06, -0.007), compared with the 'unhealthy' trajectory. CONCLUSION: Our findings suggest that maintaining a moderately healthy to very healthy diet from mid-life into older age is associated with a lower risk of frailty and supports the promotion of a healthy diet from adulthood to facilitate healthy ageing.

Exploring the Relationship Among Financial Hardship, Anxiety, and Depression in Patients With Cancer: A Longitudinal Study.

PURPOSE: Financial hardship (FH) is a complex issue in cancer care, affecting material conditions, well-being, and coping behaviors. This study aimed to longitudinally examine FH, anxiety, depressive symptoms, and their associations while incorporating social determinants of health and health care cost covariates in a sample of patients diagnosed with cancer. METHODS: This prospective, longitudinal cohort study analyzed data from 2,305 participants from the Northwestern University Improving the Management of Symptoms during and following Cancer Treatment trial. Outcomes assessed at baseline and at 3, 6, 9, and 12 months postbaseline included depressive symptoms, anxiety, and FH. Analysis involved random intercept cross-lagged panel models to explore between- and within-person effects, incorporating factors such as age, sex, insurance status, neighborhood area deprivation, health care charges, out-of-pocket costs, and health literacy. RESULTS: The cohort had a mean age of 60.7 (standard deviation [SD] = 12.7) years and was mostly female (64.9%) and White (86.2%). Correlations were found between FH and depressive symptoms (r = 0.310) and anxiety (r = 0.289). A predictive relationship was observed between FH and depressive symptoms, with baseline and 6-month depressive symptom levels predicting later FH (baseline ß = .079, P = .070; 6-month ß = .072, P = .081) and 9-month FH significantly predicting 12-month depressive symptoms (ß = .083, P = .025), even after accounting for health care charges and out-of-pocket costs. Baseline and 9-month anxiety showed a predictive relationship with subsequent FH (baseline ß = .097, P = .023; 9-month ß = .071, P = .068). CONCLUSION: FH emerged as a prominent issue, with nearly half of participants experiencing some level of FH. Depressive symptoms and anxiety were related to FH. These findings underscore the need for a comprehensive approach in cancer care that concurrently addresses anxiety, depressive symptoms, and FH, recognizing their interconnected impact.

Machine learning-driven assessment of biochemical qualities in tomato and mandarin using RGB and hyperspectral sensors as nondestructive technologies.

Estimation of fruit quality parameters are usually based on destructive techniques which are tedious, costly and unreliable when dealing with huge amounts of fruits. Alternatively, non-destructive techniques such as image processing and spectral reflectance would be useful in rapid detection of fruit quality parameters. This research study aimed to assess the potential of image processing, spectral reflectance indices (SRIs), and machine learning models such as decision tree (DT) and random forest (RF) to qualitatively estimate characteristics of mandarin and tomato fruits at different ripening stages. Quality parameters such as chlorophyll a (Chl a), chlorophyll b (Chl b), total soluble solids (TSS), titratable acidity (TA), TSS/TA, carotenoids (car), lycopene and firmness were measured. The results showed that Red-Blue-Green (RGB) indices and newly developed SRIs demonstrated high efficiency for quantifying different fruit properties. For example, the R2 of the relationships between all RGB indices (RGBI) and measured parameters varied between 0.62 and 0.96 for mandarin and varied between 0.29 and 0.90 for tomato. The RGBI such as visible atmospheric resistant index (VARI) and normalized red (Rn) presented the highest R2 = 0.96 with car of mandarin fruits. While excess red vegetation index (ExR) presented the highest R2 = 0.84 with car of tomato fruits. The SRIs such as RSI 710,600, and R730,650 showed the greatest R2 values with respect to Chl a (R2 = 0.80) for mandarin fruits while the GI had the greatest R2 with Chl a (R2 = 0.68) for tomato fruits. Combining RGB and SRIs with DT and RF models would be a robust strategy for estimating eight observed variables associated with reasonable accuracy. Regarding mandarin fruits, in the task of predicting Chl a, the DT-2HV model delivered exceptional results, registering an R2 of 0.993 with an RMSE of 0.149 for the training set, and an R2 of 0.991 with an RMSE of 0.114 for the validation set. As well as for tomato fruits, the DT-5HV model demonstrated exemplary performance in the Chl a prediction, achieving an R2 of 0.905 and an RMSE of 0.077 for the training dataset, and an R2 of 0.785 with an RMSE of 0.077 for the validation dataset. The overall outcomes showed that the RGB, newly SRIs as well as DT and RF based RGBI, and SRIs could be used to evaluate the measured parameters of mandarin and tomato fruits.

Berberine protects against sepsis-related acute lung injury in rats via PPAR-γ signaling pathway upregulation and improvement at the cellular level: Functional, biochemical, and immunohistochemistry study.

This study aimed to assess the prophylactic effects of Berberine on experimentally induced lung sepsis and examine its effects on selected cytokines, genes, and protein expression besides the histopathological evaluation. Berberine significantly reduced the wet/dry lung ratio, the broncho-alveolar lavage fluid (BALF) protein, cells, neutrophils percentage, and cytokines levels. In addition, pretreatment with Berberine decreased the myeloperoxidase (MPO) and malondialdehyde (MDA) levels and decreased gene expression of nuclear factor kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and the intracellular adhesion molecule 1 (ICAM-1) by RT-qPCR analysis, revealing Berberine's antioxidant and anti-inflammatory mode of action. Western blot analysis revealed increased peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in the Berberine pretreated group compared to the cecal ligation and puncture (CLP) group, in which the histopathological examination evidenced this improvement. In conclusion, Berberine improved lung sepsis via its PPAR-γ mediated antioxidant and anti-inflammatory effects.

Epidemiologic and clinical updates on viral infections in Saudi Arabia.

In the past two decades, the world has witnessed devastating pandemics affecting the global healthcare infrastructure and disrupting society and the economy worldwide. Among all pathogens, viruses play a critical role that is associated with outbreaks due to their wide range of species, involvement of animal hosts, easily transmitted to humans, and increased rates of infectivity. Viral disease outbreaks threaten public health globally due to the challenges associated with controlling and eradicating them. Implementing effective viral disease control programs starts with ongoing surveillance data collection and analyses to detect infectious disease trends and patterns, which is critical for maintaining public health. Viral disease control strategies include improved hygiene and sanitation facilities, eliminating arthropod vectors, vaccinations, and quarantine. The Saudi Ministry of Health (MOH) and the Public Health Authority (also known as Weqayah) in Saudi Arabia are responsible for public health surveillance to control and prevent infectious diseases. The notifiable viral diseases based on the Saudi MOH include hepatitis diseases, viral hemorrhagic fevers, respiratory viral diseases, exanthematous viral diseases, neurological viral diseases, and conjunctivitis. Monitoring trends and detecting changes in these viral diseases is essential to provide proper interventions, evaluate the established prevention programs, and develop better prevention strategies. Therefore, this review aims to highlight the epidemiological updates of the recently reported viral infections in Saudi Arabia and to provide insights into the recent clinical treatment and prevention strategies.

Renoprotective effect of a novel combination of 6-gingerol and metformin in high-fat diet/streptozotocin-induced diabetic nephropathy in rats via targeting miRNA-146a, miRNA-223, TLR4/TRAF6/NLRP3 inflammasome pathway and HIF-1α.

BACKGROUND: MiRNA-146a and miRNA-223 are key epigenetic regulators of toll-like receptor 4 (TLR4)/tumor necrosis factor-receptor-associated factor 6 (TRAF6)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway, which is involved in diabetic nephropathy (DN) pathogenesis. The currently available oral anti-diabetic treatments have been insufficient to halt DN development and progression. Therefore, this work aimed to assess the renoprotective effect of the natural compound 6-gingerol (GR) either alone or in combination with metformin (MET) in high-fat diet/streptozotocin-induced DN in rats. The proposed molecular mechanisms were also investigated. METHODS: Oral gavage of 6-gingerol (100 mg/kg) and metformin (300 mg/kg) were administered to rats daily for eight weeks. MiRNA-146a, miRNA-223, TLR4, TRAF6, nuclear factor-kappa B (NF-κB) (p65), NLRP3, caspase-1, and hypoxia-inducible factor-1 alpha (HIF-1α) mRNA expressions were measured using real-time PCR. ELISA was used to measure TLR4, TRAF6, NLRP3, caspase-1, tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1ß) renal tissue levels. Renal tissue histopathology and immunohistochemical examination of fibronectin and NF-κB (p65) were performed. RESULTS: 6-Gingerol treatment significantly reduced kidney tissue damage and fibrosis. 6-Gingerol up-regulated miRNA-146a and miRNA-223 and reduced TLR4, TRAF6, NF-κB (p65), NLRP3, caspase-1, TNF-α, IL-1ß, HIF-1α and fibronectin renal expressions. 6-Gingerol improved lipid profile and renal functions, attenuated renal hypertrophy, increased reduced glutathione, and decreased blood glucose and malondialdehyde levels. 6-Gingerol and metformin combination showed superior renoprotective effects than either alone. CONCLUSION: 6-Gingerol demonstrated a key protective role in DN by induction of miRNA-146a and miRNA-223 expression and inhibition of TLR4/TRAF6/NLRP3 inflammasome signaling. 6-Gingerol, a safe, affordable, and abundant natural compound, holds promise for use as an adjuvant therapy with metformin in diabetic patients to attenuate renal damage and stop the progression of DN.