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Schistosomiasis, caused by flatworm parasites, is a widespread disease resulting in chronic illness and fatalities globally. Given the risk of drug resistance and limited treatment options, finding new therapeutic options are crucial for managing and controlling this neglected tropical disease. In this research, various in-silico methods including Density-Functional-Theory (DFT) computations, Molecular-docking, molecular dynamics simulations and Pharmacokinetic evaluation were employed to identify ten potential inhibitors of Schistosoma mansoni HDAC8 (SmHDAC8). The modeled activities (pIC50) of these newly designed compounds (ranging between 7.110 and 6.959) surpassed that of the hit compound 19 (pIC50 = 6.445) and the standard reference control, Praziquantel (pIC50 = 5.989). Moreover, the MolDock scores (ranging between −188.964 and −158.351 kcal/mol) for these proposed compounds in the SmHDAC8 binding cavity outperformed the hit template 19 (MolDock score: −122.516 kcal/mol) and the Praziquantel (−110.245 kcal/mol). Furthermore, the conformational stability of the top three designed compounds (19a, 19i, and 19j) in the SmHDAC8 binding cavity was examined through a 100 ns of Molecular Dynamics simulation. Additionally, the drug-likeness and ADMET predictions of these compounds indicated favorable oral bioavailability and pharmacokinetic profiles. This study offers a reliable in-silico approach for identifying potential agents against Schistosomiasis.

AbstractAlzheimer’s disease is a gradual neurodegenerative condition affecting the brain, causing a decline in cognitive function by progressively damaging nerve cells over time. While a cure for Alzheimer’s remains elusive, the detection of Alzheimer’s disease (AD) through brain biomarkers is crucial to impede its advancement. High-resolution structural MRI scans, particularly T1-weighted images, are commonly used in Alzheimer’s detection. These images provide detailed information about the brain’s structure, allowing researchers and clinicians to identify abnormalities. Our study employs a deep learning methodology using T1-weighted MRI images for a binary classification task—distinguishing between AD and normal/healthy control (NC). The volumetric convolutional neural network model is deployed on pre-processed images and validated on MIRIAD datasets, achieving an impressive accuracy of 97%, surpassing other network models. Addressing the challenge of limited datasets for deep learning models, we incorporated various augmentation techniques such as rotation and rescaling, resulting in outstanding model accuracy and effective discerning between Alzheimer’s disease and normal controls.

According to various studies, different countries have different climate conditions that affect the quantity and quality of crop production. Farmers want to use novel technologies that can help them produce crops in large quantities with good quality. The greenhouse is one of the rapidly growing technologies used for the production of crops. It protects the crops from changes in external weather conditions and, hence, helps to produce good-quality crops throughout the year. This work proposes a deep study of the technologies used in the greenhouse for the monitoring and control of various environmental parameters that affect the quality and production of the crops. This work also analyses the different communication techniques, relays, and sensors used for monitoring and controlling the different greenhouse parameters. Also, give details on sensors and the advantages and disadvantages of different communication technologies so that farmers can easily understand which technology is most suitable for their greenhouse. This study helps the farmers adopt the best-suited techniques in their green houses that are cost-friendly, easy to use, and have a longer life.

With the progress in two distinct areas of nanotechnology and aptamer identification technologies, the two fields have merged to what is known as aptamer nanotechnology. Aptamers have varying properties in the biomedical field include their small size, non-toxicity, ease of manufacturing, negligible immunogenicity, ability to identify a wide range of targets, and high immobilizing capacity. Nevertheless, aptamers can utilize the distinct characteristics offered by nanomaterials like optical, magnetic, thermal, electronic properties to become more versatile and function as a novel device in diagnostics and therapeutics. This engineered aptamer conjugated nanomaterials, in turn provides a potentially new and unique properties apart from the pre-existing characteristics of aptamer and nanomaterials, where they act to offer wide array of applications in the biomedical field ranging from drug targeting, delivery of drugs, biosensing, bioimaging. This review gives comprehensive insight of the different aptamer conjugated nanomaterials and their utilization in biomedical field. Firstly, it introduces on the aptamer selection methods and roles of nanomaterials offered. Further, different conjugation strategies are explored in addition, the class of aptamer conjugated nanodevices being discussed. Typical biomedical examples and studies specifically, related to drug delivery, biosensing, bioimaging have been presented.

AA5083 with ultrafine grain structure was produced through equal channel angular pressing using different levels of ECAP tensions, underwent a series of tensile tests. The superplasticity temperature 573 K at low temperatures. This study investigate how varying the ECAP strain influences the distinctive microstructure of the alloy and its impact on deformation mechanisms within the low-temperature superplasticity range. A fraction of the high angle borders increased when the equal channel angular pressing strain was increased from 1 to 2, while the sub-grain size stayed nearly same. This was the most applicable microstructural evolution. After double passes, the material showed superplastic elongations, but after single pass, it did not show low temperature superplasticity. Upon analyzing the mechanical data using typical deformation mechanisms, it was determined that dislocation climb controlled the samples deformation after the first pass, whereas grain boundary sliding was responsible for the sample's low temperature superplasticity after the second pass. In the present study, we explored the differences in deformation mechanisms by considering the microstructures formed under various ECAP strains. Equal channel angular pressing with a BC route and an effective strain of 1∼2, we created an ultrafine-grained AA5083. A significant increase was seen in the fraction of particles measuring 1.8–3.8 μm under the current ECAP conditions. The implementation of equal channel angular pressing, there was a significant increase in the occurrence of voids with sizes ranging from 0.8 to 1.8 μm. According to the current analysis and results, if moderate superplastic elongation is guaranteed, it may be preferable to have fewer equal channel angular pressing passes than those that result in the largest elongation while taking into account cavitation damage and the low temperature superplasticity of ultrafine grained AA5083 used in commercial applications.

Summary: The paucity of preclinical models that recapitulate COVID-19 pathology without requiring SARS-COV-2 adaptation and humanized/transgenic mice limits research into new therapeutics against the frequently emerging variants-of-concern. We developed virus-free models by C57BL/6 mice receiving oropharyngeal instillations of a SARS-COV-2 ribo-oligonucleotide common in all variants or specific to Delta/Omicron variants, concurrently with low-dose bleomycin. Mice developed COVID-19-like lung pathologies including ground-glass opacities, interstitial fibrosis, congested alveoli, and became moribund. Lung tissues from these mice and bronchoalveolar lavage and lung tissues from patients with COVID-19 showed elevated levels of hyaluronic acid (HA), HA-family members, an inflammatory signature, and immune cell infiltration. 4-methylumbelliferone (4-MU), an oral drug for biliary-spasm treatment, inhibits HA-synthesis. At the human equivalent dose, 4-MU prevented/inhibited COVID-19-like pathologies and long-term morbidity; 4-MU and metabolites accumulated in mice lungs. Therefore, these versatile SARS-COV-2 ribo-oligonucleotide oropharyngeal models recapitulate COVID-19 pathology, with HA as its critical mediator and 4-MU as a potential therapeutic for COVID-19.

Plants have been utilized by humans throughout history for a variety of purposes, including sustenance and medicinal intentions. Since ancient times, wheatgrass has been utilized as a type of microgreen for therapeutic purposes. Phenolic flavonoids, vitamins, minerals, proteins and enzymes are all abundant in wheatgrass. These nutrients and bioactive substances enhanced wheatgrass's therapeutic efficacy and made it a powerful antioxidant agent for the treatment of a range of diseases. It has been shown to have a wide variety of pharmacological potentials, including an antioxidative potential that helps to neutralize free radicals, anti-cancer, anti-ulcer, anti-diabetic, anti-arthritic, anti-microbial action, and many more. However, there is a dearth of scientific evidence to back up wheatgrass's possible pharmacological effects and clinical value. To investigate its clinical utility for human welfare, in-depth research studies are needed. Through this analysis of the review literature, an attempt has been made to explain wheatgrass and its therapeutic potentials.

ABSTRACT: Herbal therapy is a type of alternative or complementary medicine that uses natural ingredients to alleviate health issues including mental illness. Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by a slow loss of memory coupled with shrinkage of brain tissue, localized loss of neurons, primarily in the hippocampus and basal forebrain, and decreased levels of the central cholinergic neurotransmitter acetylcholine. Bacopa monnieri is also known as brahmi which is very well known for memory enhancer and Piper nigrum is work as bioavailability enhancer which will reduce the dose frequency and increase effectiveness on other drugs. So, this study's goal was to look at the physicochemical parameters, phytochemical characteristics, and synergistic memory enhancing effect of B. monnieri with P. nigrum a natural bioenhancer on mice with scopolamine-induced learning and memory deficits. Six group of six animal were treated respectively, once daily with ethanolic extract of B. monnieri (EEBM) (200 mg/kg), ethanolic extract of P. nigrum (EEPN) 200 mg/kg, Combination of EEBM (100 mg/kg) with EEPN (100 mg/kg), donepezil 1 mg/kg via oral dosing and were given intraperitoneal (ip) injection of scopolamine 1 mg/kg daily to induce cognitive deficits. The tests for locomotor activity, stair climbing, and pole climbing were utilised to evaluate the learning and memory components. Additionally examined were dopamine, serotonin (5-HT) and other physiological elements. The results showed combination of Brahmi and black pepper shows pole climbing, actophotometer activity, staircase activity that showed better therapeutic advantages for improving mice's antiamnesic activity as compared to single extract of Brahmi. In response, the treated groups with combined extract emitted noticeably more dopamine and serotonin. When compared to illness control, the extract's ability to improve memory was highly significant (P< 0.001). These findings indicate that the combination of Brahmi and black pepper improved memory and hence could serve as a viable therapeutic target for the treatment of neurodegenerative illnesses.

Abstract Nano‐scale laser beam size and its shape information are essential parameters in most optics‐based precision measurements and nano‐scale material processing. It is also quite challenging to measure nano‐size optical beams accurately for both open experiments and at compact workplace of microscope due to various instrumental factors. Outside of the visible spectrum, usually wavelength‐sensitive fluorescence markers and composite materials are used to read the laser beam profile. In this article, a cost‐effective carbon nano‐particles (CNPs) film has been developed from candle soot. Furthermore, the developed bio‐carbon soot film is encapsulated with optically transparent composite polymer on aqueous media to measure sub‐micron size spot of a low‐power laser. Field emission scanning electron microscopy, optical spectrum analysis, Fourier transform infrared spectroscopy, UV‐visible spectroscopy, differential scanning calorimetry and thermogravimetric analysis techniques have been performed to characterize the developed CNPs film and optimized its functionality. The fabricated film has been used to measure sub‐micron laser beam size. Due to the wide absorption spectrum of the developed bio‐CNPs film, the sensitivity region for measurement lies within both visible and beyond the visible spectrum.

Optimization of nature friendly and consistent developments of the green synthesis of nanoparticles have engrossed encouraged in nanotechnology since of its marvelous incentive in modifying metals into nano size to its probable use for human welfares. The present report reveals the young leaves of Pancratium telanganense was exposed for extra-cellular bio-synthesis of silver nanoparticles (AgNPs) and its antibacterial actions against bacterial pathogens The eco-friendly biosynthesized AgNps optimized then considered by UV spectrum, FTIR, TEM. Then formed AgNPs were confirmed against bacterial test organisms. The young leaves of Pancratium telanganense were establish to be a noble fabricator of AgNPs. Expansion maximizes exhibited absorbance of 420–425 nm at pH-7, 25 °C with 1 mM AgNO3 concentration and 100 mg of leaves powder crude extract. Auxiliary TEM discovered the types of formation of irregular, fine discrete nanoparticles with size ranging between 20 to 35 nm, the FTIR illustrations the bands at 1644 and 153 8 cm−1 consistent to the necessary ambiances of bands of proteins. Antibacterial activities against bacterial pathogens exhibited good results have shown the maximum inhibition zone about 18 mm and 17 mm respectively at 60 μl of AgNps.

Abstract In recent years, the outbreak of infectious disease caused by Zika Virus (ZIKV) has posed a major threat to global public health, calling for the development of therapeutics to treat ZIKV disease. Several possible druggable targets involved in virus replication have been identified. In search of additional potential inhibitors, we screened 2895 FDA-approved compounds using Non-Structural Protein 5 (NS5) as a target utilizing virtual screening of in-silco methods. The top 28 compounds with the threshold of binding energy −7.2 kcal/mol value were selected and were cross-docked on the three-dimensional structure of NS5 using AutoDock Tools. Of the 2895 compounds screened, five compounds (Ceforanide, Squanavir, Amcinonide, Cefpiramide, and Olmesartan_Medoxomil) ranked highest based on filtering of having the least negative interactions with the NS5 and were selected for Molecular Dynamic Simulations (MDS) studies. Various parameters such as RMSD, RMSF, Rg, SASA, PCA and binding free energy were calculated to validate the binding of compounds to the target, ZIKV-NS5. The binding free energy was found to be −114.53, −182.01, −168.19, −91.16, −122.56, and −150.65 kJ mol−1 for NS5-SFG, NS5-Ceforanide, NS5-Squanavir, NS5-Amcinonide, NS5-Cefpiramide, and NS5-Ol_Me complexes respectively. The binding energy calculations suggested Cefpiramide and Olmesartan_Medoxomil (Ol_Me) as the most stable compounds for binding to NS5, indicating a strong rationale for their use as lead compounds for development of ZIKV inhibitors. As these drugs have been evaluated on pharmacokinetics and pharmacodynamics parameters only, in vitro and in vivo testing and their impact on Zika viral cell culture may suggest their clinical trials on ZIKV patients.

Background: Monkeypox is a highly infectious zoonotic disease, often resulting in complications ranging from respiratory illnesses to vision loss. The escalating global incidence of its cases demands prompt attention, as the absence of a proven post-exposure treatment underscores the criticality of developing an effective vaccine.Methods: Interactions of the viral proteins with TLR2 and TLR4 were investigated to assess their immunogenic potentials. Highly immunogenic proteins were selected and subjected to epitope mapping for identifying B-cell and MHC class I and II epitopes. Epitopes with high antigenicity were chosen, considering global population coverage. A multi-target, multi-epitope vaccine peptide was designed, incorporating a beta-defensin 2 adjuvant, B-cell epitopes, and MHC class I and II epitopes.Results: The coordinate structure of the engineered vaccine was modeled and validated. In addition, its physicochemical properties, antigenicity, allergenicity, and virulence traits were evaluated. Molecular docking studies indicated strong interactions between the vaccine peptide and the TLR2 receptor. Furthermore, molecular dynamics simulations and immune simulation studies reflected its potent cytosolic stability and robust immune response dynamics induced by the vaccine.Conclusion: This study explored an innovative structure-guided approach in the use of immunoinformatics and reverse vaccinology in pursuit of a novel multi-epitope vaccine against the highly immunogenic monkeypox viral proteins. The simulation studies indicated the engineered vaccine candidate to be promising in providing prophylaxis to the monkeypox virus; nevertheless, further in vitro and in vivo investigations are required to prove its efficacy.

The popularity and acceptance of ayurveda drugs are increasing day by day worldwide due to their low cost and no side effects. Due to high demand of herbal raw materials for the manufacturing of different classical as well as phytoformulation there is scope for adulteration of original drugs with chemically or physically resemble raw drugs. Standardization process conforms the identity, quality and purity of herbal drugs, which can be done by different procedures and by using sophisticated techniques. HPTLC method has advantages over other techniques due to its suitability for herbal drugs, low cost, reproducibility and it is easy to operate as well. An HPTLC method has been developed for the quality testing of Avipattikar churna (AVC) and to discriminate any kind of alteration in drugs composition.

Neurological ailments, including stroke, Alzheimer’s disease (AD), epilepsy, Parkinson’s disease (PD), and other related diseases, have affected around 1 billion people globally to date. PD stands second among the common neurodegenerative diseases caused as a result of dopaminergic neuron loss in the midbrain’s substantia nigra regions. It affects cognitive and motor activities, resulting in tremors during rest, slow movement, and muscle stiffness. There are various traditional approaches for the management of PD, but they provide only symptomatic relief. Thus, a survey for finding new biomolecules or substances exhibiting the therapeutic potential to patients with PD is the main focus of present-day research. Medicinal plants, herbal formulations, and natural bioactive molecules have been gaining much more attention in recent years as synthetic molecules orchestrate a number of undesired effects. Several in vitro, in vivo, and in silico studies in the recent past have demonstrated the therapeutic potential of medicinal plants, herbal formulations, and plant-based bioactives. Among the plant-based bioactives, polyphenols, terpenes, and alkaloids are of particular interest due to their potent anti-inflammatory, antioxidant, and brain-health-promoting properties. Further, there are no concise, elaborated articles comprising updated mechanism-of-action-based reviews of the published literature on potent, recently investigated (2019–2023) medicinal plants, herbal formulations, and plant based-bioactive molecules, including polyphenols, terpenes, and alkaloids, as a method for the management of PD. Therefore, we designed the current review to provide an illustration of the efficacious role of various medicinal plants, herbal formulations, and bioactives (polyphenols, terpenes, and alkaloids) that can become potential therapeutics against PD with greater specificity, target approachability, bioavailability, and safety to the host. This information can be further utilized in the future to develop several value-added formulations and nutraceutical products to achieve the desired safety and efficacy for the management of PD.

Thermal power plants use coal as a fuel to create electricity while wasting a significant amount of energy as heat. If the heat and power plants are combined and used in cogeneration systems, it is possible to reuse the waste heat and hence enhance the overall efficiency of the power plant. In order to minimize production costs while taking system constraints into account, it is important to find out the optimal operating point of power and heat for each unit. Combined heat and power production is now widely used to improve thermal efficiency, lower environmental emissions, and reduce power generation costs. In order to determine the best solutions to the combined heat and power economic dispatch problem, several traditional as well as innovative heuristic optimization approaches were employed. This study offers a thorough analysis of the use of heuristic optimization techniques for the solution of the combined heat and power economic dispatch problem. In this proposed work, the most well-known heuristic optimization methods are examined and used for the solution of various generating unit systems, such as 4, 7, 11, 24, 48, 84, and 96, taking into account various constraints. This study analyzes how various evolutionary approaches are performed for various test systems. The heuristic methodologies’ best outcomes for various case studies with restrictions are contrasted.

One of the most cutting-edge technologies over the years is the Internet of Things (IoT), which is a major force behind the paradigm shift away from conventional medical practises. The goal of IoT-based eHealth is to provide healthcare services that are more effective and individualised through continuous data exchange between linked devices and enhanced data analytics. The IoT and decision-making systems are the main areas of focus of this programme, which seeks to deliver intelligent and proactive healthcare. By considering the huge array of physiological characteristics and applying potent analytical tools like cluster analysis, it is possible to obtain more insight into health-data. In this study, e-health technologies and remote patient monitoring were developed to assist patients in avoiding hospital visits, especially during viral epidemics. This project will use IoT and artificial intelligence (AI) technology to address these problems. The study's objective is to select the most appropriate and effective number of hidden layers and activation function types for the deep net (NN). Describe the patient data sent using IoT protocols next. NN analyses the information from the patient's medical sensors to choose the optimal option. The diagnosis is then communicated to the physician. The proposed technology enables patients to autonomously recognise and forecast the sickness while also supporting clinicians in remote disease discovery and analysis without requiring patients to attend the hospital.

Protein modification by ubiquitin fold modifier 1 (UFM1), termed ufmylation, regulates various physiological and pathological processes. Among emerging UFM1 targets, UFM1 binding protein 1 (UFBP1) is the first identified ufmylation substrate. Recent clinical and animal studies have demonstrated the pivotal roles of UFBP1 in development, hematopoiesis, intestinal homeostasis, chondrogenesis, and neuronal development, which has been linked to its function in maintaining endoplasmic reticulum (ER) homeostasis. However, the importance of UFBP1 ufmylation in these cellular and physiological processes has yet to be determined. It has been proposed that ufmylation of lysine 268 (267 in humans) in UFBP1 plays a critical role in mediating the effects of the ufmylation pathway. In this study, we for the first time probe the pathophysiological significance of UFBP1 ufmylation in vivo by creating and characterizing a mouse UFBP1 knockin (KI) model in which the lysine 268 of UFBP1, the amino acid accepting UFM1, was mutated to arginine. Our results showed that the K268R mutation reduced the total ufmylated proteins without altering the expression levels of individual ufmylation enzymes in mouse embryonic fibroblasts. The K268R mutation did not alter ER stress–stimuli–induced ER stress signaling or cell death in mouse embryonic fibroblasts. The homozygous KI mice were viable and morphologically indistinguishable from their littermate wild–type controls up to one year of age. Serial echocardiography revealed no cardiac functional impairment of the homozygous KI mice. Furthermore, the homozygous KI mice exhibited the same susceptibility to dextran sulfate sodium (DSS) –induced colitis as wild-type mice. Taken together, these results suggest that UFBP1 K268 is dispensable for ER stress response, embryonic development, cardiac homeostasis under physiological conditions, and intestinal homeostasis under pathological conditions. Our studies call for future investigations to understand the biological function of UFBP1 ufmylation and offer a new mouse model to determine the roles of UFBP1 ufmylation in different tissues under stress conditions.

Abstract Background Cylinder blasts can inflict multi-system life-threatening injuries to one or many persons simultaneously if they are nearby. The explosion in high-pressure equipment produces injuries due to its varied effects. Cases have been reported where the blast occurred in balloon gas cylinder, oxyacetylene gas cylinder, oxygen cylinder, coffee machine, and compressor of a split air conditioner (AC). Most of the cases are accidental. The investigation into the blast circumstances is of utmost importance to find out the manner and device involved. Case presentation Here, we present a report of two cases where victims suffered blast injuries at the same location due to the explosion of two different capacity liquefied petroleum gas (LPG) domestic cylinder and died on the spot. Conclusion The investigation into the blast circumstances is of utmost importance to find out the manner and device involved. Malpractice involving use of cylinder to fill another one might be dangerous for the person involved and present in the vicinity. This practice should be discouraged by lay person.

Abstract Intestinal Paneth cells are professional exocrine cells that play crucial roles in maintenance of homeostatic microbiome, modulation of mucosal immunity, and support for stem cell self-renewal. Dysfunction of these cells may lead to the pathogenesis of human diseases such as inflammatory bowel disease (IBD). Cdk5 activator binding protein Cdk5rap3 (also known as C53 and LZAP) was originally identified as a binding protein of Cdk5 activator p35. Although previous studies have indicated its involvement in a wide range of signaling pathways, the physiological function of Cdk5rap3 remains largely undefined. In this study, we found that Cdk5rap3 deficiency resulted in very early embryonic lethality, indicating its indispensable role in embryogenesis. To further investigate its function in the adult tissues and organs, we generated intestinal epithelial cell (IEC)-specific knockout mouse model to examine its role in intestinal development and tissue homeostasis. IEC-specific deletion of Cdk5rap3 led to nearly complete loss of Paneth cells and increased susceptibility to experimentally induced colitis. Interestingly, Cdk5rap3 deficiency resulted in downregulation of key transcription factors Gfi1 and Sox9, indicating its crucial role in Paneth cell fate specification. Furthermore, Cdk5rap3 is highly expressed in mature Paneth cells. Paneth cell-specific knockout of Cdk5rap3 caused partial loss of Paneth cells, while inducible acute deletion of Cdk5rap3 resulted in disassembly of the rough endoplasmic reticulum (RER) and abnormal zymogen granules in the mature Paneth cells, as well as loss of Paneth cells. Together, our results provide definitive evidence for the essential role of Cdk5rap3 in Paneth cell development and maintenance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus with single positive-strand RNA, having glycoproteins projection on envelopes so reveals a halo-like appearance or corona. Coronavirus is of four types: (1) α-coronavirus (α-COV); (2) β-coronavirus (β-COV); (3) δ-coronavirus (δ-COV); and (4) γ-coronavirus (γ-COV) and belongs to family Coronaviridae and subfamily Coronavirinae. Coronaviruses are the normal pathogens that cause broad band of gastrointestinal and respiratory diseases in domestic as well as wild animals such as pigs, birds, and rodents. Coronavirus is highly infectious in case of elders for mortality rate. The elder peoples are at 2-fold higher risk as compared to the younger population and the greater part of the population dying from coronavirus disease (COVID-19) is male. The virus enters into the body by the mouth, eyes, or nose, then particles march inside of the body by different pathways and affect vital organs in severe ways such as liver, heart muscle, blood vessels, kidneys, central nervous system, etc. Right now, the only solution to avoid COVID-19 infection is “precautions.” Different companies of different countries at different steps are in race to develop effective medicines for treatment and management of the same. Here, in this review, we tried to give an overview of all about SARS-CoV-2, COVID-19 infection, pathophysiology, mechanisms, and various treatment trials.

The aim of this study was to evaluate the antistress activity of rhizomes ethanolic extract of Curculigo orchioides Gaertn in vivo, using mice with stress-induced injury. The effect of Curculigo orchioides on motor coordination, spontaneous locomotor activity, immobility time, and analgesia was evaluated in mice using standard procedure. The ethanolic extract of Curculigo orchioides at dose levels, i.e., 100 and 200 mg/kg shows pronounced antistress activity evidenced by reduced immobility time in forced swimming and tail test. It also improved motor coordination and enhanced analgesic effect compared to standard diazepam. The Curculigo orchioides was found to be a antistress activity.

Currently, a disease name as corona (COVID-19) has become a serious problem around the globe. As of December 2020, the disease has spread to over 213 countries and territories around the world and 2 international conveyances, with over 79,850,900 confirmed cases and over 1,751,705 deaths. The ailment (COVID-19) is instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CoV impacts on the respiratory tract and causes infection that may be minor or deadly. Several studies reveal that coronavirus can remain live on nonliving surfaces (glass, metal, or plastic) for up to 9 days, but it may be denatured with many disinfectants having alcohol, benzalkonium chloride, sodium hypochlorite, etc., within 1 min. As we know, there is no fruitful therapy or medication for COVID-19 so early precaution and prevention is the only solution to break the chain of coronavirus. By using different types of disinfectants, we can inhibit the growth of this novel corona disease.

Severe symptomatic tricuspid regurgitation (TR) with right heart failure is associated with significant morbidity and mortality. Medical therapy is often ineffective and surgical correction is not feasible due to prohibitive perioperative risk. Transcatheter caval valve implantation (CAVI) is an evolving therapeutic option for this condition. It refers to the heterotopic placement of a valve into the inferior vena cava alone or with a second valve in the superior vena cava to restrict the backflow from the failing tricuspid valve. We hereby describe a patient with previous mitral valve surgery with chronic severe TR who underwent successful CAVI at our institute.

Intestinal IL-22 has important regulatory effects on the barrier and intestinal diseases and its production is controlled by the intestinal microbiome. Here the authors show that intestinal immune cell production of IL-22 is regulated by short chain fatty acids via an aryl hydrocarbon receptor and HIF1α-mediated mechanism that protects mice from intestinal inflammation.

Currently, there is a great demand for the development of nanomedicine aided wound tissue regeneration via silver doped nanoceuticals. Unfortunately, very little research is being carried out on antioxidants-doped silver nanometals and their interaction on the signaling axis during the bio-interface mechanism. In this study, c-phycocyanin primed silver nano hybrids (AgcPCNP) were prepared and analyzed for properties such as cytotoxicity, metal decay, nanoconjugate stability, size expansion, and antioxidant features. Fluctuations in the expression of marker genes during cell migration phenomena in in vitro wound healing scenarios were also validated. Studies revealed that physiologically relevant ionic solutions did not exhibit any adverse effects on the nanoconjugate stability. However, acidic, alkali, and ethanol solutions completely denatured the AgcPCNP conjugates. Signal transduction RT2PCR array demonstrated that genes associated with NFĸB- and PI3K-pathways were significantly (p < 0.5%) altered between AgcPCNP and AgNP groups. Specific inhibitors of NFĸB (Nfi) and PI3K (LY294002) pathways confirmed the involvement of NFĸB signaling axes. In vitro wound healing assay demonstrated that NFĸB pathway plays a prime role in the fibroblast cell migration. In conclusion, the present investigation revealed that surface functionalized AgcPCNP accelerated the fibroblast cell migration and can be further explored for wound healing biomedical applications.

Wound healing responses play a major role in chronic inflammation, which affects millions of people around the world. One of the daunting tasks of creating a wound-healing drug is finding equilibrium in the inflammatory cascade. In this study, the molecular and cellular mechanisms to regulate wound healing are explained, and recent research is addressed that demonstrates the molecular and cellular events during diabetic wound healing. Moreover, a range of factors or agents that facilitate wound healing have also been investigated as possible targets for successful treatment. It also summarises the various advances in research findings that have revealed promising molecular targets in the fields of therapy and diagnosis of cellular physiology and pathology of wound healing, such as neuropeptides, substance P, T cell immune response cDNA 7, miRNA, and treprostinil growth factors such as fibroblast growth factor, including thymosin beta 4, and immunomodulators as major therapeutic targets.

IRE1 and PERK, both important mediators of the unfold protein response pathway, are differentially regulated during plasma cell differentiation. Here the authors show that an ufmylation target, Ufbp1, suppresses PERK to stimulate plasma cell development and is induced by the IRE1/XBP1 pathway to promote ER expansion .

Children under the age of five constitute around 7% of the total U.S. population, and represent a segment of the population that is totally dependent on others for day-to-day activities. A significant proportion of this population spends time in some form of day care arrangement while their parents are away from home. Accounting for those children during emergencies is of high priority, which requires a broad understanding of the locations of such day care centers. As concentrations of at risk population, the spatial location of day care centers is critical for any type of emergency preparedness and response (EPR). However, until recently, the U.S. emergency preparedness and response community did not have access to a comprehensive spatial database of day care centers at the national scale. This paper describes an approach for the development of the first comprehensive spatial database of day care center locations throughout the U.S. utilizing a variety of data harvesting techniques to integrate information from widely disparate data sources followed by geolocating for spatial precision. In the context of disaster management, such spatially refined demographic databases hold tremendous potential for improving high-resolution population distribution and dynamics models and databases.

Human pancreatic cancer does not respond to immune check point blockade immunotherapy. One key feature of pancreatic cancer is the association between its progression and chronic inflammation. Emerging evidence supports a key role for the JAK-STAT pathway in pancreatic cancer inflammation. We aimed at testing the hypothesis that sustained JAK-STAT signaling suppresses cytotoxic T lymphocyte (CTL) activation to counteract anti-PD-1 immunotherapy-induced CTL activity in pancreatic cancer. We show that human pancreatic carcinomas express high level of PD-L1 and exhibit low level of CTL infiltration. JAK-STAT inhibitor Ruxolitinib selectively inhibits STAT1 and STAT3 activation and increases CTL infiltration to induce a Tc1/Th1 immune response in the tumor microenvironment in an orthotopic pancreatic cancer mouse model. Ruxilitinib-mediated tumor suppressive efficacy diminishes in T-cell-deficient mice. Pancreatic tumor grows significantly faster in IFNγ-deficient mice. However, neutralizing IFNγ does not alter tumor growth but diminishes Ruxolitinib-induced tumor suppression in vivo, indicating that lymphocytes and IFNγ are essential for Ruxolitinib-induced host antitumor immune response. Both type I and type II interferons upregulate PD-L1 expression through the JAK-STAT signaling pathway in mouse pancreatic tumor cells. Tumor cells respond to activated T cells by activating STAT3. The inhibition of STAT3 downregulates immune suppressive cytokines production by tumor cells, resulting in increased T cell activation and effector function. Consequently, Ruxolitinib significantly improves the efficacy of anti-PD-1 immunotherapy. Our data demonstrate that Ruxolitinib is effective in the inhibition of systemic inflammation in the tumor microenvironment and therefore upregulates CTL infiltration and activation to overcome pancreatic cancer resistance to anti-PD-1 immunotherapy.

Carbidopa is a drug that blocks conversion of levodopa to dopamine outside of central nervous system (CNS) and thus inhibits unwanted side effects of levodopa on organs located outside of CNS during management of Parkinson's Disease (PD). PD is associated with increased expression of inflammatory genes in peripheral and central nervous system (CNS), infiltration of immune cells into brain, and increased numbers of activated/memory T cells. Animal models of PD have shown a critical role of T cells in inducing pathology in CNS. However, the effect of carbidopa on T cell responses in vivo is unknown. In this report, we show that carbidopa strongly inhibited T cell activation in vitro and in vivo. Accordingly, carbidopa mitigated myelin oligodendrocyte glycoprotein peptide fragment 35-55 (MOG-35-55) induced experimental autoimmune encephalitis (EAE) and collagen induced arthritis in animal models. The data presented here suggest that in addition to blocking peripheral conversion of levodopa, carbidopa may inhibit T cell responses in PD individuals and implicate a potential therapeutic use of carbidopa in suppression of T cell mediated pathologies.

Direct smear microscopy of sputum forms the mainstay of TB diagnosis in resource-limited settings. Stained sputum smear slides can serve as a ready-made resource to transport sputum for molecular drug susceptibility testing. However, bio-safety is a major concern during transport of sputum/stained slides and for laboratory workers engaged in processing Mycobacterium tuberculosis infected sputum specimens. In this study, a bio-safe USP (Universal Sample Processing) concentration-based sputum processing method (Bio-safe method) was assessed on 87 M. tuberculosis culture positive sputum samples. Samples were processed for Ziehl-Neelsen (ZN) smear, liquid culture and DNA isolation. DNA isolated directly from sputum was subjected to an IS6110 PCR assay. Both sputum DNA and DNA extracted from bio-safe ZN concentrated smear slides were subjected to rpoB PCR and simultaneously assessed by DNA sequencing for determining rifampin (RIF) resistance. All sputum samples were rendered sterile by Bio-safe method. Bio-safe smears exhibited a 5% increment in positivity over direct smear with a 14% increment in smear grade status. All samples were positive for IS6110 and rpoB PCR. Thirty four percent samples were RIF resistant by rpoB PCR product sequencing. A 100% concordance (κ value = 1) was obtained between sequencing results derived from bio-safe smear slides and bio-safe sputum. This study demonstrates that Bio-safe method can address safety issues associated with sputum processing, provide an efficient alternative to sample transport in the form of bio-safe stained concentrated smear slides and can also provide information on drug (RIF) resistance by direct DNA sequencing.

Guanylyl cyclase-C (GC-C) agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation. Oral administration of sildenafil caused increased cGMP levels in mouse intestinal epithelium demonstrating that blocking cGMP-breakdown is an alternative approach to increase cGMP in the gut. Both linaclotide and sildenafil reduced proliferation and increased differentiation in colon mucosa, indicating common target pathways. The homeostatic effects of cGMP required gut turnover since maximal effects were observed after 3 days of treatment. Neither linaclotide nor sildenafil treatment affected intestinal transit or water content of fecal pellets in healthy mice. To test the effectiveness of cGMP elevation in a functional motility disorder model, mice were treated with dextran sulfate sodium (DSS) to induce colitis and were allowed to recover for several weeks. The recovered animals exhibited slower transit, but increased fecal water content. An acute dose of sildenafil was able to normalize transit and fecal water content in the DSS-recovery animal model, and also in loperamide-induced constipation. The higher fecal water content in the recovered animals was due to a compromised epithelial barrier, which was normalized by sildenafil treatment. Taken together our results show that sildenafil can have similar effects as linaclotide on the intestine, and may have therapeutic benefit to patients with CIC, IBS-C, and post-infectious IBS.

The Ufm1 conjugation system is an ubiquitin-like modification system that consists of Ufm1, Uba5 (E1), Ufc1 (E2), and less defined E3 ligase(s) and targets. The biological importance of this system is highlighted by its essential role in embryogenesis and erythroid development, but the underlying mechanism is poorly understood. UFBP1 (Ufm1 binding protein 1, also known as DDRGK1, Dashurin and C20orf116) is a putative Ufm1 target, yet its exact physiological function and impact of its ufmylation remain largely undefined. In this study, we report that UFBP1 is indispensable for embryonic development and hematopoiesis. While germ-line deletion of UFBP1 caused defective erythroid development and embryonic lethality, somatic ablation of UFBP1 impaired adult hematopoiesis, resulting in pancytopenia and animal death. At the cellular level, UFBP1 deficiency led to elevated ER (endoplasmic reticulum) stress and activation of unfolded protein response (UPR), and consequently cell death of hematopoietic stem/progenitor cells. In addition, loss of UFBP1 suppressed expression of erythroid transcription factors GATA-1 and KLF1 and blocked erythroid differentiation from CFU-Es (colony forming unit-erythroid) to proerythroblasts. Interestingly, depletion of Uba5, a Ufm1 E1 enzyme, also caused elevation of ER stress and under-expression of erythroid transcription factors in erythroleukemia K562 cells. By contrast, knockdown of ASC1, a newly identified Ufm1 target that functions as a transcriptional co-activator of hormone receptors, led to down-regulation of erythroid transcription factors, but did not elevate basal ER stress. Furthermore, we found that ASC1 was associated with the promoters of GATA-1 and Klf1 in a UFBP1-dependent manner. Taken together, our findings suggest that UFBP1, along with ASC1 and other ufmylation components, play pleiotropic roles in regulation of hematopoietic cell survival and differentiation via modulating ER homeostasis and erythroid lineage-specific gene expression. Modulating the activity of this novel ubiquitin-like system may represent a novel approach to treat blood-related diseases such as anemia.

The incidences of infections caused by an aerobic Gram-negative bacterium, Acinetobacter baumannii are very common in hospital environments. It usually causes soft tissue infections including urinary tract infections and pneumonia. It is difficult to treat due to acquired resistance to available antibiotics is well known. In order to design specific inhibitors against one of the important enzymes, peptidyl-tRNA hydrolase from Acinetobacter baumannii, we have determined its three-dimensional structure. Peptidyl-tRNA hydrolase (AbPth) is involved in recycling of peptidyl-tRNAs which are produced in the cell as a result of premature termination of translation process. We have also determined the structures of two complexes of AbPth with cytidine and uridine. AbPth was cloned, expressed and crystallized in unbound and in two bound states with cytidine and uridine. The binding studies carried out using fluorescence spectroscopic and surface plasmon resonance techniques revealed that both cytidine and uridine bound to AbPth at nanomolar concentrations. The structure determinations of the complexes revealed that both ligands were located in the active site cleft of AbPth. The introduction of ligands to AbPth caused a significant widening of the entrance gate to the active site region and in the process of binding, it expelled several water molecules from the active site. As a result of interactions with protein atoms, the ligands caused conformational changes in several residues to attain the induced tight fittings. Such a binding capability of this protein makes it a versatile molecule for hydrolysis of peptidyl-tRNAs having variable peptide sequences. These are the first studies that revealed the mode of inhibitor binding in Peptidyl-tRNA hydrolases which will facilitate the structure based ligand design.

The aim of this study was to investigate the effects of ethanolic extract of Pueraria tuberosa (PT) on sexual behaviour and androgenic activity. Male albino rats were divided into four groups of six animals each: control group 1 (2% acacia solution), PT-treated group 2 (50 mg/Kg), PT-treated group 3 (100 mg/Kg), and PT-treated group 4 (150 mg/Kg). Sexual behavior of male rats in the presence of a female rat was recorded. The treated groups were evaluated for sexual parameters. The extract was characterized using LC-MS. The effect of treatment on anabolic and weight of secondary sexual organs was determined. The histological changes in section of testis and epididymis after treatment were observed. Sperm count in epididymis and fructose content in seminal vesicles were also measured. Levels of hormones like FSH, LH, and T were determined. A dose-dependent increase in sexual behaviors was evidenced in the animals of extract treated groups. Increase in testis weight was recorded in PT. At the highest dose PT also affects the hormones level. The four compounds namely puerarin, daidzein, biochanin-A and formononetin were identified in ethanolic extract using LC-MS. It concluded that PT extract possesses androgenic effect and it significantly increased the sexual behaviour and hormones level.

A common procedure in human cytotoxic T lymphocyte (CTL) adoptive transfer immunotherapy is to expand tumor-specific CTLs ex vivo using CD3 mAb prior to transfer. One of the major obstacles of CTL adoptive immunotherapy is a lack of CTL persistence in the tumor-bearing host after transfer. The aim of this study is to elucidate the molecular mechanisms underlying the effects of stimulation conditions on proliferation and survival of tumor-specific CTLs.Tumor-specific CTLs were stimulated with either CD3 mAb or cognate Ag and analyzed for their proliferation and survival ex vivo and persistence in tumor-bearing mice. Although both Ag and CD3 mAb effectively induced the cytotoxic effecter molecules of the CTLs, we observed that Ag stimulation is essential for sustained CTL proliferation and survival. Further analysis revealed that Ag stimulation leads to greater proliferation rates and less apoptosis than CD3 mAb stimulation. Re-stimulation of the CD3 mAb-stimulated CTLs with Ag resulted in restored CTL proliferative potential, suggesting that CD3 mAb-induced loss of proliferative potential is reversible. Using DNA microarray technology, we identified that survivin and ifi202, two genes with known functions in T cell apoptosis and proliferation, are differentially induced between Ag- and CD3 mAb-stimulated CTLs. Analysis of the IFN-γ signaling pathway activation revealed that Ag stimulation resulted in rapid phosphorylation of STAT1 (pSTAT1), whereas CD3 mAb stimulation failed to activate STAT1. Chromatin immunoprecipitation revealed that pSTAT1 is associated with the promoters of both survivin and ifi202 in T cells and electrophoresis mobility shift assay indicated that pSTAT1 directly binds to the gamma activation sequence element in the survivin and ifi202 promoters. Finally, silencing ifi202 expression significantly decreased T cell proliferation.Our findings delineate a new role of the IFN-γ signaling pathway in regulating T cell proliferation and apoptosis through upregulating survivin and ifi202 expression.