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Alzheimer’s disease (AD) is a neurodegenerative disorder, and its pathogenesis is not fully known. Although there are several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid-β plaques, neurofibrillary tangles, and oxidative stress, none of them completely explain the origin and progression of AD. Emerging evidence suggests that gut microbiota and epigenetics can directly influence the pathogenesis of AD via their effects on multiple pathways, including neuroinflammation, oxidative stress, and amyloid protein. Various gut microbes such as Actinobacteria, Bacteroidetes, E. coli, Firmicutes, Proteobacteria, Tenericutes, and Verrucomicrobia are known to play a crucial role in the pathogenesis of AD. These microbes and their metabolites modulate various physiological processes that contribute to AD pathogenesis, such as neuroinflammation and other inflammatory processes, amyloid deposition, cytokine storm syndrome, altered BDNF and NMDA signaling, impairing neurodevelopmental processes. Likewise, epigenetic markers associated with AD mainly include histone modifications and DNA methylation, which are under the direct control of a variety of enzymes, such as acetylases and methylases. The activity of these enzymes is dependent upon the metabolites generated by the host’s gut microbiome, suggesting the significance of epigenetics in AD pathogenesis. It is interesting to know that both gut microbiota and epigenetics are dynamic processes and show a high degree of variation according to diet, stressors, and environmental factors. The bidirectional relation between the gut microbiota and epigenetics suggests that they might work in synchrony to modulate AD representation, its pathogenesis, and progression. They both also provide numerous targets for early diagnostic biomarkers and for the development of AD therapeutics. This review discusses the gut microbiota and epigenetics connection in the pathogenesis of AD and aims to highlight vast opportunities for diagnosis and therapeutics of AD.

Cardiovascular diseases (CVD) are the leading cause of mortality, morbidity, and “sudden death” globally. Environmental and lifestyle factors play important roles in CVD susceptibility, but the link between environmental factors and genetics is not fully established. Epigenetic influence during CVDs is becoming more evident as its direct involvement has been reported. The discovery of epigenetic mechanisms, such as DNA methylation and histone modification, suggested that external factors could alter gene expression to modulate human health. These external factors also influence our gut microbiota (GM), which participates in multiple metabolic processes in our body. Evidence suggests a high association of GM with CVDs. Although the exact mechanism remains unclear, the influence of GM over the epigenetic mechanisms could be one potential pathway in CVD etiology. Both epigenetics and GM are dynamic processes and vary with age and environment. Changes in the composition of GM have been found to underlie the pathogenesis of metabolic diseases via modulating epigenetic changes in the form of DNA methylation, histone modifications, and regulation of non-coding RNAs. Several metabolites produced by the GM, including short-chain fatty acids, folates, biotin, and trimethylamine-N-oxide, have the potential to regulate epigenetics, apart from playing a vital role in normal physiological processes. The role of GM and epigenetics in CVDs are promising areas of research, and important insights in the field of early diagnosis and therapeutic approaches might appear soon.

COVID-19 was first reported in December 2019 in the Wuhan city of China, and since then it has spread worldwide taking a heavy toll on human life and economy. COVID-19 infection is commonly associated with symptoms like coughing, fever, and shortness of breath, besides, the reports of muscle pain, anosmia, hyposmia, and loss of taste are becoming evident. Recent reports suggest the pathogenic invasion of the SARS-CoV-2 into the CNS, that could thereby result in devastating long term complications, primarily because some of these complications may go unnoticed for a long time. Evidence suggest that the virus could enter the CNS through angiotensin-converting enzyme-2 (ACE-2) receptor, neuronal transport, haematogenous route, and nasal route via olfactory bulb, cribriform plate, and propagates through trans-synaptic signalling, and shows retrograde movement into the CNS along nerve fiber. COVID-19 induces CNS inflammation and neurological degenerative damage through a diverse mechanism which includes ACE-2 receptor damage, cytokine-associated injury or cytokine storm syndrome, secondary hypoxia, demyelination, blood–brain barrier disruption, neurodegeneration, and neuroinflammation. Viral invasion into the CNS has been reported to show association with complications like Parkinsonism, Alzheimer’s disorder, meningitis, encephalopathy, anosmia, hyposmia, anxiety, depression, psychiatric symptoms, seizures, stroke, etc. This review provides a detailed discussion of the CNS pathogenesis of COVID-19. Authors conclude that the COVID-19 cannot just be considered as a disorder of the pulmonary or peripheral system, rather it has a significant CNS involvement. Therefore, CNS aspects of the COVID-19 should be monitored very closely to prevent long term CNS complications, even after the patient has recovered from COVID-19.

To develop an amino acid prodrug of acetaminophen with comparable therapeutic profile and less hepatotoxicity than acetaminophen. Acetaminophen prodrug was synthesized by esterification between the carboxyl group of amino acid glycine and hydroxyl group of acetaminophen. Analgesic, antipyretic, ulcer healing, and hepatotoxic activities were performed on Wistar rats in this study. Prodrug showed a 44% inhibition in writhings as compared to 53.3% of acetaminophen. Acetaminophen also offered highest antipyretic activity. Prodrug showed gastroprotective and hepatoprotective effects as it reduced the gastric lesions by 32.1% (P < 0.01) and significantly prevented the rise in liver enzymes (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and bilirubin). The most notable effect of prodrug was in preventing the depletion of hepatic glutathione (GSH), which is reduced by acetaminophen. Prodrug showed hepatoprotective and gastroprotective effects, although the therapeutic efficacy was compromised. Prodrug was successful in preventing a decrease in GSH, thereby exhibiting promising results in the field of prodrug designing to avoid the toxic effects of acetaminophen.

The presence of voids in cement concrete may lead to a reduction in its performance when exposed to high shrinkage and settlement. This study focused on utilization of bacteria for improving the performance by reducing the voids in the concrete. Bacillus family bacteria were found to be the great healers for the concrete. Bacillus megaterium bacteria of bacillus family with a concentration of 10 8 CFU have been utilized in the current study. A total of 48 specimens were cast and tested for their mechanical strength and water absorption after 7 and 28 days of curing. The test results indicate that the compressive, split tensile and flexural strengths increased to 12.91%, 10.28% and 9.02% respectively after 28 days of curing as compared to standard M30 grade concrete mix. The water absorption value of bacterial concrete was also found to be less as compared to the standard concrete mix. This is because of the filling of the cracks in concrete due to calcite precipitation produced by the Bacillus megaterium bacteria. Therefore, the Bacillus megaterium bacteria of bacillus family can be effectively utilized to improve the mechanical strength by reducing the voids.

It is almost impossible to avoid the development of cracks on the surface of the concrete even after using the best quality material and workmanship. These cracks may result into the degradation of concrete in terms of its strength and durability. Therefore it becomes utmost important to seal these cracks so that the devastating effects of the degrading agencies that may enter into the concrete through these cracks can be reduced or eliminated. This paper presents a review on the effects of the concentration of various bacillus family bacteria on the strength and durability properties of concrete. The bacteria with a concentration of 10 0 CFU to 10 8 has been considered in this review. This paper also outlines the self-healing ability of different bacillus family bacteria. Self-healing refers to the cracks in concrete, through addition of the bacillus family bacteria to the concrete mix and checks the impacts of bacillus family bacteria on the strength and durability properties of the concrete.

Diabetes mellitus is a chronic metabolic disorder and has been associated with cognitive dysfunction. In our earlier study, chronic Urtica dioica (UD) treatment significantly ameliorated diabetes induced associative and spatial memory deficit in mice. The present study was designed to explore the effect of UD leaves extract on muscarinic cholinergic system, which has long been known to be involved in cognition. Streptozotocin (STZ) (50 mg/kg, i.p., consecutively for 5 days) was used to induce diabetes followed by treatment with UD extract (50 mg/kg, oral) or rosiglitazone (5 mg/kg, oral) for 8 weeks. STZ-induced diabetic mice showed significant reduction in hippocampal muscarinic acetylcholine receptor-1 and choline acetyltransferase expressions. Chronic diabetes significantly up-regulated the protein expression of acetylcholinesterase associated with oxidative stress in hippocampus. Besides, STZ-induced diabetic mice showed hypolocomotion with up-regulation of muscarinic acetylcholine receptor-4 expression in striatum. Chronic UD treatment significantly attenuated the cholinergic dysfunction and oxidative stress in the hippocampus of diabetic mice. UD had no effect on locomotor activity and muscarinic acetylcholine receptor-4 expression in striatum. In conclusion, UD leaves extract has potential to reverse diabetes mediated alteration in muscarinic cholinergic system in hippocampus and thereby improve memory functions.

Vaginal candidiasis (VC), a common recurrent gynaecological disorder affects almost 70% of women. Development of resistance to anti-fungal agents exacerbates the need for new treatments against Candida infections. The objective of the current work was to develop ethosomal vesicles (EVs) and EV hydrogel of Butea monosperma seed oil (BMSO) for treatment of vaginal candidiasis, as BMSO has demonstrated fungicidal and bactericidal activities. EVs, formulated by ethanol injection-sonication method, used Phospholipon®90G and ethanol as excipients and were optimized by Box-Behnken design (BBD). BMSO ( X 1 ), phospholipid ( X 2 ) and ethanol concentration ( X 3 ) were selected as input variables, while vesicle size ( Y 1 ), polydispersity index ( PDI ) ( Y 2 ) and percent entrapment efficiency (% EE ) ( Y 3 ) were taken as response variables. The size of optimized EVs determined by dynamic light scattering technique was found to be 249 ± 2.6 nm; PDI was 0.301 ± 0.013; % EE determined by high-speed centrifugation method was 53.84 ± 1.98%. Field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HR-TEM) unveiled vesicles of rhombic dodecahedral shape with smooth, sealed structure. The EVs, incorporated into carbopol gel, demonstrated non-Newtonian behaviour on a rotary type rheometer. Minimal inhibitory concentration (MIC ) determination by broth microdilution method revealed MIC of EVs and hydrogel to be 2.5 times less, as compared to BMSO against Candida albicans  ( C.albicans ). Anti- candidal activities determined using agar well diffusion method demonstrated better zone of inhibition for hydrogel vis-a-vis BMSO. Pharmacodynamic evaluation conducted on Balb/c female mice manifested a comparable decrease in fungal burden by EVs and EV hydrogel to marketed clotrimazole. Histopathology of vaginal tissue of treated groups showed no or mild inflammation with normal skin structure. The results disclosed EVs and EV hydrogel to possess better anti-fungal activity vis-a-vis BMSO and can be explored as potential alternative herbal product for VC.

Background The vitreous humor is a transparent, gelatinous mass whose main constituent is water. It plays an important role in providing metabolic nutrient requirements of the lens, coordinating eye growth and providing support to the retina. It is in close proximity to the retina and reflects many of the changes occurring in this tissue. The biochemical changes occurring in the vitreous could provide a better understanding about the pathophysiological processes that occur in vitreoretinopathy. In this study, we investigated the proteome of normal human vitreous humor using high resolution Fourier transform mass spectrometry. Results The vitreous humor was subjected to multiple fractionation techniques followed by LC-MS/MS analysis. We identified 1,205 proteins, 682 of which have not been described previously in the vitreous humor. Most proteins were localized to the extracellular space (24%), cytoplasm (20%) or plasma membrane (14%). Classification based on molecular function showed that 27% had catalytic activity, 10% structural activity, 10% binding activity, 4% cell and 4% transporter activity. Categorization for biological processes showed 28% participate in metabolism, 20% in cell communication and 13% in cell growth. The data have been deposited to the ProteomeXchange with identifier PXD000957. Conclusion This large catalog of vitreous proteins should facilitate biomedical research into pathological conditions of the eye including diabetic retinopathy, retinal detachment and cataract.

The pathogenesis of Alzheimer’s disease (AD) is not fully understood which limits the availability of safer and more efficient therapeutic strategies for the management of AD. There has been growing interest in recent years in exploring the potential of herbal medicines as a source of safer and alternative therapeutic strategies for the management of AD. This study aims to discover the mechanism of Hypericum perforatum in the management of AD using network pharmacology and molecular docking approach. The results of network pharmacology suggest that 39 bioactive molecules of H. perforatum target 127 genes associated with AD, amongst which ATP-dependent translocase, acetylcholinesterase, amyloid-β precursor protein, β-secretase 1, carbonic anhydrase 2, dipeptidyl peptidase 4, epidermal growth factor receptor, tyrosine-protein phosphatase non-receptor type 1, α-synuclein, and vascular endothelial growth factor A seems to be the prominent target of these molecules. Further, the results of molecular docking predicted amentoflavone, I3,II8-biapigenin, rutin, miquelianin, quercetin, luteolin, and nicotiflorin as a promising modulator of target proteins which were determined from network pharmacology to be associated with AD. Our findings suggest that H. perforatum could be a safer and more promising alternative therapeutic strategy for the management of AD by targeting multiple pathways of AD pathogenesis.