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The human intestine contains an intricate ecological community of dwelling bacteria, referred as gut microbiota (GM), which plays a pivotal role in host homeostasis. Multiple factors could interfere with this delicate balance, including genetics, age, antibiotics, as well as environmental factors, particularly diet, thus causing a disruption of microbiota equilibrium (dysbiosis). Growing evidences support the involvement of GM dysbiosis in gastrointestinal (GI) and extra-intestinal cardiometabolic diseases, namely obesity and diabetes. This review firstly overviews the role of GM in health and disease, then critically reviews the evidences regarding the influence of dietary polyphenols in GM based on preclinical and clinical data, ending with strategies under development to improve efficiency of delivery. Although the precise mechanisms deserve further clarification, preclinical and clinical data suggest that dietary polyphenols present prebiotic properties and exert antimicrobial activities against pathogenic GM, having benefits in distinct disorders. Specifically, dietary polyphenols have been shown ability to modulate GM composition and function, interfering with bacterial quorum sensing, membrane permeability, as well as sensitizing bacteria to xenobiotics. In addition, can impact on gut metabolism and immunity and exert anti-inflammatory properties. In order to overcome the low bioavailability, several different approaches have been developed, aiming to improve solubility and transport of dietary polyphenols throughout the GI tract and deliver in the targeted intestinal regions. Although more research is still needed, particularly translational and clinical studies, the biotechnological progresses achieved during the last years open up good perspectives to, in a near future, be able to improve the use of dietary polyphenols modulating GM in a broad range of disorders characterized by a dysbiotic phenotype.

The aims of this work to optimize and validate a RP-HPLC method to quantify erastin (ERT) and lenalidomide (LND) in mesoporous silica nanoparticles (MSNs). The Design of Experiments (DoE) strategy optimized the RP-HPLC method. The independent variables were buffer ratio, buffer pH, flow rate and injection volume. The dependent variables were retention time (Rt), Peak area, and resolution between the peaks of the analytes. The optimized conditions were: buffer ratio 68% and methanol 32%, flow rate 0.8 mL/min, buffer pH 5.8, and injection volume 10 µL. The ICH Q2(R1) recommendations were followed in the validation of the optimized RP-HPLC method. The method demonstrated linearity of more than 0.99 for both ERT and LND. The LOD and LOQ were 0.75 and 1.62 ng/mL for ERT; for LND 31.25 and 50 ng/mL. The specificity of the established RP-HPLC method was unaffected by the MSNs matrix. The drugs-loaded MSNs were analyzed using the suggested RP-HPLC technique. The % entrapment efficiency of ERT and LND was found to be 72.65 and 79.50%, and drug loading of ERT and LND was found to be 14 and 17% in MSNs, respectively. The optimized RP-HPLC method was used to check the in-vitro drug release of the ERT and LND from the ERT-LND@MSNs. Surface properties of synthesized MSNs was checked through particle and SEM analysis. The developed analytical method was eco-friendly according to AGREE analysis and GAPI analysis.

Activation of the innate immune system is commonly associated with depression. Immunomodulatory drugs may have efficacy for depressive symptoms that are co-morbidly associated with inflammatory disorders. We report a large-scale re-analysis by standardized procedures (mega-analysis) of patient-level data combined from 18 randomized clinical trials conducted by Janssen or GlaxoSmithKline for one of nine disorders (N = 10,743 participants). Core depressive symptoms (low mood, anhedonia) were measured by the Short Form Survey (SF-36) or the Hospital Anxiety and Depression Scale (HADS), and participants were stratified into high (N = 1921) versus low-depressive strata based on baseline ratings. Placebo-controlled change from baseline after 4–16 weeks of treatment was estimated by the standardized mean difference (SMD) over all trials and for each subgroup of trials targeting one of 7 mechanisms (IL-6, TNF-α, IL-12/23, CD20, COX2, BLγS, p38/MAPK14). Patients in the high depressive stratum showed modest but significant effects on core depressive symptoms (SMD = 0.29, 95% CI [0.12–0.45]) and related SF-36 measures of mental health and vitality. Anti-IL-6 antibodies (SMD = 0.8, 95% CI [0.20–1.41]) and an anti-IL-12/23 antibody (SMD = 0.48, 95% CI [0.26–0.70]) had larger effects on depressive symptoms than other drug classes. Adjustments for physical health outcome marginally attenuated the average treatment effect on depressive symptoms (SMD = 0.20, 95% CI: 0.06–0.35), but more strongly attenuated effects on mental health and vitality. Effects of anti-IL-12/23 remained significant and anti-IL-6 antibodies became a trend after controlling for physical response to treatment. Novel immune-therapeutics can produce antidepressant effects in depressed patients with primary inflammatory disorders that are not entirely explained by treatment-related changes in physical health.

Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), an ellagitannin, is one of the major bioactive compounds present in various plants. Ellagitannins belong to the hydrolyzable tannins, a group of polyphenols. Corilagin shows broad-spectrum biological, and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, and antitumor actions. Natural compounds possessing antitumor activities have attracted significant attention for treatment of cancer. Corilagin has shown inhibitory activity against the growth of numerous cancer cells by prompting cell cycle arrest at the G2/M phase and augmented apoptosis. Corilagin-induced apoptosis and autophagic cell death depends on production of intracellular reactive oxygen species in breast cancer cell line. It blocks the activation of both the canonical Smad and non-canonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways. The potential apoptotic action of corilagin is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, and Bcl-2 Bax. In nude mice, corilagin suppressed cholangiocarcinoma growth and downregulated the expression of Notch1 and mammalian target of rapamycin. The aim of this review is to summarize the anticancer efficacy of corilagin with an emphasis on the molecular mechanisms involving various signaling pathways in tumor cells.

Immune system is amongst the most radiosensitive system to radiation-induced cellular and molecular damage. Present study was focused on the evaluation of radioprotective efficacy of a novel secondary metabolite, N -acetyl tryptophan glucoside (NATG), isolated from a radioresistant bacterium Bacillus sp. INM-1 using murine macrophage J774A.1 cells experimental model. Radioprotective efficacy of NATG against radiation-induced DNA damage and apoptosis was estimated using phosphatidyl-serine-externalization Annexin V-PI and Comet assay analysis. Radiation-induced cell death is the outcome of oxidative stress caused by free radicals. Therefore, perturbations in antioxidant enzymes i.e., superoxide dismutase (SOD), catalase, glutathione-s-transferase (GST) and GSH activities in irradiated and NATG pre-treated irradiated J774A.1 cells were studied. Results of the present study demonstrated that NATG pre-treated (0.25 µg/ml) irradiated (20 Gy) cells showed significant ( p  < 0.05) reduction in apoptotic cells index at 4–48 h as compared to radiation alone cells. Comet assay exhibited significant protection to radiation-induced DNA damage in J774A.1 cells. Significantly shortened DNA tail length, increased % Head DNA contents and lower olive tail moment was observed in NATG pre-treated irradiated cells as compared to radiation alone cells. Further, significant increase in catalase (~ 3.9 fold), SOD (67.52%), GST (~ 1.9 fold), and GSH (~ 2.5 fold) levels was observed in irradiated cells pre-treated with NATG as compared to radiation-alone cells. In conclusion, current study suggested that NATG pre-treatment to irradiated cells enhanced antioxidant enzymes in cellular milieu that may contribute to reduce oxidative stress and decrease DNA damage which resulted to significant reduction in the cell death of irradiated macrophages.

Ecchordosis physaliphora (EP) is a benign notochordal remnant, which is often an incidental finding; however, it can rarely present with neurological symptoms. We performed a systematic review of the literature for cases of symptomatic EP published in PubMed, Web of Science and Embase from January 1982 to May 2023. This is the largest review to date and revealed 60 cases including ours. Headache (55%) and CSF rhinorrhea (32%) were the most frequent clinical manifestations. The majority of symptomatic EP lesions were located in the prepontine region (77%) and required surgical resection (75%). EP should be considered in patients with neurologic symptoms in the setting of prepontine or posterior sphenoid sinus lesions. While symptomatic patients often require surgical intervention, rare cases may respond to oral corticosteroids.

In this study, we studied cancer pattern among male and females' patients reported to this tertiary care hospital located in this region. Results A total of 4409 cancer cases were reported at our hospital during the years 2017 and 2018, out of which males accounted for 2504 (56.79%) and females for 1905 (43.2%) of cases with male to female ratio of 1.31:1. The possible risk factor for occurrence of breast cancer was contributed by stress in the form of higher education and occupation, late menopause, history of induced abortion, first-degree family history of the disease and body mass index (17). Early marriages, infection with HPV, multiple partners & lack of genital hygiene are some of the contributory factors for the high incidence of this cancer (19).

Race and ethnicity have been shown to affect patient symptoms and outcomes in various diseases, including autoimmune neurological diseases. There has not yet been a comprehensive study on how race and ethnicity affects all causes of encephalitis in adults, including both infectious and autoimmune sources. Our research team used patient records from the past and from two major cities to collect data on patient demographics, symptoms, diagnostic and imaging findings, treatment received while hospitalized, and outcomes/recovery. Patients were categorized by race/ethnicity into two groups for this initial study; White or ethnic minority (including Black, Hispanic, and Asian patients). We analyzed the data to see if there were major differences in any factors between the two groups. The total number of patients was 599, with 52.1% being White and 47.9% of an ethnic minority. We found that White patients tended to present at a much older age and with memory gaps. Ethnic minority patients were sicker when they presented to the hospital in terms of other diseases they co-presented with, as well as initial imaging and lab findings. Our ethnic minority patients had worse outcomes in terms of neurological recovery and functional status by their discharge. A separate analysis showed that abnormal magnetic resonance imaging (MRI) results and a certain level of consciousness upon admission were indicative of worse outcomes by discharge. Our study revealed that ethnic minority patients with encephalitis are more likely to present younger and with more severe illness upon hospitalization, which may be a potential reason for worse functional outcomes. More work needs to be done to differentiate symptoms and outcomes between the two groups based on the cause of encephalitis (infectious vs. autoimmune). This study has also identified abnormal MRI and level of consciousness upon admission as potential predictors of worse outcomes, which should be further studied.

H-bonded liquid crystals (HBLCs) are newly synthesized with PyBF viz., (4-pyridyl)-benzylidene-4′-fluoro aniline as the proton acceptor which is non-mesogenic and alkyloxy benzoic acids viz., nOBAs (n = 3, 12) as the mesogenic proton donors. The H-bond formed is confirmed by FTIR spectroscopy. Polarizing Optical Microscopy confirmed the H-bonded compound’s mesomorphic textures, and the thermal analysis is carried out using a Differential Scanning Calorimeter. The influence of fluorine atom on mesomorphic stability is studied. The nonlinear optical properties of the H-bonded compound is studied using DFT theoretical approach. This work supports the SDG-9 of the United Nations.Article HighlightsNew heterocyclic H-bonded liquid crystals is synthesized.The fluorine atoms influence the mesomorphism.Decreased clearing and crystallization temperatures are achievedMesomorphism is realized at ambient temperatures.The H-bonded liquid crystals exhibit good nonlinear optical properties.

After publishing a research article in the year 2019, a cam-shaped cylinder was introduced, and the results expressed its ability to prevent the vortex from shedding. This makes the cam-shaped cylinder a better performer than the circular cylinder. This work is an extension of past work with the aim of further reducing drag by attaching a backward splitter plate to a cam-shaped cylinder. In an attempt to decrease drag and regulate the wake regime more efficiently than the traditional splitter plate control devices, a splitter plate flow departure control device is presented in this paper for a low Reynolds number flow range (Re = 50–200). It has been noted that when plate length increases, integral parameters like drag, lift, and Strouhal number do not change monotonically. The Strouhal number (St) increases with a drop in D2/Deq, but the average drag reduces with a rise in Re and a decrease in D2/Deq, respectively. In terms of decreased drag, the current cam-shaped cylinders attached to a rearward splitter plate have shown their superiority to other bluff bodies.