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The present study aimed to characterize the biosurfactants synthesized by lactic acid bacteria (LAB) obtained from fermented foods, optimize the conditions for increasing the yield of biosurfactants and explore their antimicrobial and antibiofilm potential. Out of the 26 LAB isolates, isolate BS2 showed the highest biosurfactant production as indicated in the oil displacement test, drop collapse and emulsification activity. BS2 was identified as Lactiplantibacillus plantarum 1625 using 16S-rRNA gene sequencing and phylogenetic analysis. The biosurfactant produced by BS2 was identified as an anionic glycol-lipo-proteins by employing Fourier Transform Infrared Spectroscopy (FTIR) and Gas Chromatography–Mass Spectrometry (GC–MS) analysis. The biosurfactants produced by L. plantarum 1625 demonstrated strong antibacterial and antibiofilm characteristics against pathogenic strains such as Staphylococcus aureus MTCC 1049, Escherichia coli MTCC 1587, and Pseudomonas putida MTCC 1655. The minimal inhibition concentration value of antibacterial activity was found to be 0.1 mg/mL with the inhibition percentage ranging from 90 to 95%. Further, the effect of temperature, pH, and substrate composition on biosurfactant production was also studied to enhance it production using the Box–Behnken Design approach of Response surface methodology (RSM). Application of biosurfactant led to a considerable decrease in biofilm-forming harmful bacteria, as proven by scanning electron microscopy analysis. The results highlight the potential uses of biosurfactants in distinct industries, and biotechnological contexts, especially in the creation of new antimicrobial and antibiofilm agents.

Colorectal cancer is the second leading cause of cancer-related deaths. In 2018, there were an estimated 1.8 million cases, and this number is expected to increase to 2.2 million by 2030. Despite its prevalence, the current therapeutic option has a lot of side effects and limitations. Therefore, this study was designed to employ a computational approach for the identification of anti-cancer inhibitors against colorectal cancer using Resveratrol derivatives. Initially, the pass prediction spectrum of 50 derivatives was conducted and selected top seven compounds based on the maximum pass prediction score. After that, a comprehensive analysis, including Lipinski Rule, pharmacokinetics, ADMET profile study, molecular orbitals analysis, molecular docking, molecular dynamic simulations, and MM-PBSA binding free energy calculations. The reported binding affinity ranges of Resveratrol derivatives from molecular docking were -6.1 kcal/mol to -7.9 kcal/mol against the targeted receptor of human armadillo repeats domain of adenomatous polyposis coli (APC) (PDB ID: 3NMW). Specifically, our findings reported that two compounds [(03) Resveratrol 3-beta-mono-D-glucoside, and (29) Resveratrol 3-Glucoside] displayed the highest level of effectiveness compared to all other derivatives (-7.7 kcal/mol and -7.9 kcal/mol), and favorable drug-likeness, and exceptional safety profiles. Importantly, almost all the molecules were reported as free from toxic effects. Subsequently, molecular dynamic simulations conducted over 100ns confirmed the stability of the top two ligand-protein complexes. These findings suggest that Resveratrol derivatives may be effective drug candidate to manage the colorectal cancer. However, further experimental research, such as in vitro/in vivo studies, is essential to validate these computational findings and confirm their practical value.

IntroductionThe research focuses on Rhododendron ferrugineum L., Nepal’s national flower and Uttarakhand’s state tree, thriving in high-altitude mountain ecosystems.Methodology and ResultA study conducted in Himachal Pradesh (Latitude: N 31° 6’ 2.0088”, Longitude: E 77° 10’ 29.9136”) identified leaf anomalies resembling rust-like manifestations in R. ferrugineum. These anomalies were traced back to the pathogenic fungus Curvularia tuberculata, marking the first documented case of its impact on R. ferrugineum in India.DiscussionThis discovery emphasizes the need for vigilant monitoring, disease management research, and conservation efforts to protect the cultural and ecological significance of this iconic shrub. Beyond its immediate findings, the study introduces a novel dimension to Indian flora by associating C. tuberculata with R. ferrugineum, historically linked to monocotyledonous crops. The research methodology combines traditional microscopic examination with advanced genomic sequencing and phylogenetic analysis, enhancing pathogen identification accuracy.Future prospectIn a broader context, this research aligns with the United Nations Sustainable Development Goals (SDGs) by highlighting the importance of environmental preservation, conservation, and sustainable management. It underscores the intricate interplay between biodiversity, cultural heritage, and the need for holistic solutions. Overall, this study calls for proactive measures to protect R. ferrugineum’s cultural and ecological heritage and emphasizes the significance of interdisciplinary approaches in addressing emerging ecological threats.

Objective: To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington’s disease (HD).Methods: We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability.Results: HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain’s motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD.Conclusion: The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world, affecting an estimated 50 million individuals. The nerve cells become impaired and die due to the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs). Dementia is one of the most common symptoms seen in people with AD. Genes, lifestyle, mitochondrial dysfunction, oxidative stress, obesity, infections, and head injuries are some of the factors that can contribute to the development and progression of AD. There are just a few FDA-approved treatments without side effects in the market, and their efficacy is restricted due to their narrow target in the etiology of AD. Therefore, our aim is to identify a safe and potent treatment for Alzheimer’s disease. We chose the ursolic acid (UA) and its similar compounds as a compounds’ library. And the ChEMBL database was adopted to obtain the active and inactive chemicals against Keap1. The best Quantitative structure-activity relationship (QSAR) model was created by evaluating standard machine learning techniques, and the best model has the lowest RMSE and greatest R2 (Random Forest Regressor). We chose pIC50 of 6.5 as threshold, where the top five potent medicines (DB06841, DB04310, DB11784, DB12730, and DB12677) with the highest predicted pIC50 (7.091184, 6.900866, 6.800155, 6.768965, and 6.756439) based on QSAR analysis. Furthermore, the top five medicines utilize as ligand molecules were docked in Keap1’s binding region. The structural stability of the nominated medications was then evaluated using molecular dynamics simulations, RMSD, RMSF, Rg, and hydrogen bonding. All models are stable at 20 ns during simulation, with no major fluctuations observed. Finally, the top five medications are shown as prospective inhibitors of Keap1 and are the most promising to battle AD.

BackgroundA deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (hBD-2) and cathelicidin LL-37] in the defense against SARS-CoV-2, it became important to identify the damaging missense mutations in the genes of these molecules and study their role in the pathogenesis of COVID-19.MethodsWe conducted a comprehensive analysis with multiple in silico approaches to identify the damaging missense SNPs for hBD-2 and LL-37; moreover, we applied docking methods and molecular dynamics analysis to study the impact of the filtered mutations.ResultsThe comprehensive analysis reveals the presence of three damaging SNPs in hBD-2; these SNPs were predicted to decrease the stability of hBD-2 with a damaging impact on hBD-2 structure as well. G51D and C53G mutations were located in highly conserved positions and were associated with differences in the secondary structures of hBD-2. Docking-coupled molecular dynamics simulation analysis revealed compromised binding affinity for hBD-2 SNPs towards the SARS-CoV-2 spike domain. Different protein–protein binding profiles for hBD-2 SNPs, in relation to their native form, were guided through residue-wise levels and differential adopted conformation/orientation.ConclusionsThe presented model paves the way for identifying patients prone to COVID-19 in a way that would guide the personalization of both the diagnostic and management protocols for this serious disease.

Nardostachys jatamansi (D. Don) DC is a highly valued medicinal herb that has been used in traditional medicinal systems for its remedial effects. Owing to the over-exploitation and unethical trade of N. jatamansi, the accelerating global demand of herbal products from this plant cannot be satisfied by the conventional extraction approach. In view of the progressive demand and incredible biological potential of herb, the present research was designed to optimize various extraction parameters for microwave-assisted extraction (MAE). The extracts obtained from the traditional and green approach were also assessed for the recovery of secondary metabolites and anti-Alzheimer’s potential. Various parameters like microwave power, temperature, and time of irradiation were optimized for MAE using Box Behkhen Design (BBD) The scanning electron microscopy of different plant samples was also done to observe the effect of microwave radiations. Further, the metabolite profiling of different extracts was also done by gas chromatography-mass spectrometry (GC-MS) analysis. Also the different behavioral and biochemical parameters along with acetylcholinesterase (AChE) inhibitory potential were assessed to evaluate the anti-Alzheimer’s potential. Optimized parameters for MAE were found to be as microwave power 187.04 W, temperature 90°C, and irradiation time 20 min. The extract yield in MAE was significantly enhanced as compared to the conventional method. Also, the total phenolic content and total flavonoid content (TFC) were improved pointedly from 32.13 ± 0.55 to 72.83 ± 1.1 mg of GAE/g of extract and 21.7 ± 0.85 to 39.21 ± 0.7 mg of RUE/g of extract respectively. Later, the GC-MS analysis of various extracts confirmed the enhancement in the concentration of various sesquiterpenes like jatamansone, spirojatamol, valerenal, valeric acid, globulol, nootkatone and steroidal compounds such as sitosterol, ergosterol, stigmastanone, etc. in the optimized extract. A significant improvement in anti-Alzheimer’s potential was also observed owing to the better concentration of secondary metabolites in the optimized microwave extract. From the current findings, it could be concluded that the MAE could be a successful and green alternative for the extraction and recovery of secondary metabolites from the selected medicinal herb.

Groundwater contamination through potentially harmful metals (PHMs) is an environmental hazard in Pakistan with significant human health risk reports. The current research was conducted in Sheikhupura District, which is a major industrial site in Punjab, Pakistan. According to the Punjab Directorate of Industries in Pakistan, there are a total of 748 industries in this area. These industries produce a lot of waste and effluent, which contaminate the environment with harmful and toxic materials. Continuous irrigation with industrial effluent and sewage sludge may make groundwater sources vulnerable. Therefore, we collected 243 groundwater samples from community tube wells to investigate the groundwater quality cconcerning PHM contaminations in the study area. This research presents the values of pH, total dissolved solids (TDS), electrical conductivity (EC), and potentially harmful metals (PHMs) like arsenic (As), manganese (Mn), lead (Pb), zinc (Zn), copper (Cu), nickel (Ni), and iron (Fe). PHMs such as As (91%), Mn (14%), Pb (97%), Fe (45%), Zn (15%), in these samples were beyond the permitted limit recommended by the world health organization (WHO). Principal component analysis (PCA) results with total variability of (60%) reveal that the groundwater sources of the study area are contaminated about 30.9, 31.3, and 37.6% of contaminations of groundwater sources of this study are resulted from geogenic sources, anthropogenic sources, or both geogenic and anthropogenic sources, respectively. Such sources may include rock-water interaction, mining actions, agricultural practices, domestic sewage, and industrial effluent in the study area. Saturation indices show that the aquifers of the study area are saturated with lead hydroxide, zinc hydroxide, and goethite minerals, indicating that these minerals have a vital role in the contamination of groundwater. Health risk assessment results predicted that the non-carcinogenic risk (HQ) values of PHMs were found within the permissible limit (

This study aims to increase the aqueous solubility of ciprofloxacin (CPN) to improve oral bioavailability. This was carried out by formulating a stable formulation of the Self-Emulsifying Drug Delivery System (SEDDS) using various ratios of lipid/oil, surfactant, and co-surfactant. A pseudo-ternary phase diagram was designed to find an area of emulsification. Eight formulations (F1-CPN–F8-CPN) containing oleic acid oil, silicone oil, olive oil, castor oil, sunflower oil, myglol oil, polysorbate-80, polysorbate-20, PEO-200, PEO-400, PEO-600, and PG were formulated. The resultant SEDDS were subjected to thermodynamic study, size, and surface charge studies to improve preparation. Improved composition of SEDDS F5-CPN containing 40% oil, 60% polysorbate-80, and propylene glycol (Smix ratio 6: 1) were thermodynamically stable emulsions having droplet size 202.6 nm, charge surface -13.9 mV, and 0.226 polydispersity index (PDI). Fourier transform infra-red (FT-IR) studies revealed that the optimized formulation and drug showed no interactions. Scanning electron microscope tests showed the droplets have an even surface and spherical shape. It was observed that within 5 h, the concentration of released CPN from optimized formulations F5-CPN was 93%. F5-CPN also showed a higher antibacterial action against S. aurous than free CPN. It shows that F5-CPN is a better formulation with a good release and high antibacterial activity.

Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma.Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4.Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events.Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.

Osteoporosis (OP) is a serious health problem, and the most popular therapeutic strategy for OP is hormone replacement (estrogen); however, it increases the risk of reproductive cancers. Hydroxyapatite (HA) nanoparticles have a similar chemical structure to the bone mineral component and can be used as a new remedy for OP. This study was designed to investigate the osteoporosis-protective potential of nano zinc hydroxyapatite (ZnHA-NPs) and/or estradiol (E2) combined therapy. A total of 35 adult female rats were assigned into five groups (n = 7): 1) control group; 2) ovariectomized group (OVX); 3) OVX received oral estradiol replacement therapy (OVX/E2); 4) OVX received ZnHA replacement therapy (OVX/ZnHA); and 5) OVX received both estradiol and ZnHA-NPs combined therapy (OVX/E2+ZnHA). After 3 months of treatment, serum bone markers and estrogen level, oxidative/antioxidant, and inflammatory cytokines were determined. Additionally, femoral expression of estrogen receptors alpha and beta (ESR1; ESR2), receptor activator of nuclear factor-kappa B (RANKL) ligand, osteoprotegerin (OPG), bone mineral density (BMD), histological alterations, and immunohistochemical expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) were assessed. ALP, PINP, Ca, and P concentrations improved significantly (p < 0.05) in all treatment groups, especially in the OVX/E + ZnHA group. MDA and NO were higher in OVX rats, while SOD activity and GSH were lower (p < 0.05). E2 alone or with ZnHA-NPs restored the estimated antioxidant molecules and cytokines toward normal levels in OVX rats (p < 0.05). On the other hand, E2 and ZnHA increased OPG and OC expression in femurs while decreasing ESR1, ESR2, and NF-kB expression (p < 0.05). The combination treatment was superior in the restoration of normal femoral histoarchitecture and both cortical and trabecular BMD (p < 0.05). Overall, the combined therapy of OVX/E2+ZnHA was more effective than the individual treatments in attenuating excessive bone turnover and preventing osteoporosis.

There are more than two hundred fifty different types of cancers, that are diagnosed around the world. Prostate cancer is one of the suspicious type of cancer spreading very fast around the world, it is reported that in 2018, 29430 patients died of prostate cancer in the United State of America (USA), and hence it is expected that one out of nine men diagnosed with this severe disease during their lives. Medical science has identified cancer at several stages and indicated genes mutations involved in the cancer cell progressions. Genetic implications have been studied extensively in cancer cell growth. So most efficacious drug for prostate cancer is highly required just like other severe diseases for men. So nutraceutical companies are playing major role to manage cancer disease by the recommendation of best natural products around the world, most of these natural products are isolated from plant and mushrooms because they contain several chemoprotective agents, which could reduce the chances of development of cancer and protect the cells for further progression. Some nutraceutical supplements might activate the cytotoxic chemotherapeutic effects by the mechanism of cell cycle arrest, cell differentiation procedures and changes in the redox states, but in other, it also elevate the levels of effectiveness of chemotherapeutic mechanism and in results, cancer cell becomes less reactive to chemotherapy. In this review, we have highlighted the prostate cancer and importance of nutraceuticals for the control and management of prostate cancer, and the significance of nutraceuticals to cancer patients during chemotherapy.

Macleaya cordata (M. cordata) is a herbal plant that has abundant amounts of sanguinarine, which has many biomedical properties. The effects of M. cordata dietary supplementation on the productive performance, some blood constituents, and growth-related genes' expression were evaluated in turkey. M. cordata extract was dietary supplemented to turkey at levels of 25, 50, and 100 ppm and a control group. Growth performance measurements (FBW, ADG, and FCR) and production efficiency factor for turkey (BPEF) were similar (p > 0.05) in all supplemented groups. M. cordata has no adverse effects (p > 0.05) on the birds' health regarding hematological (Hb, RBCs, WBCs, and PCV) and blood biochemical indices evaluating liver function, kidney function, and lipid profile. Moreover, the mRNA expression of growth-related genes, such as growth hormone receptor (GHR), insulin-like growth factor 1 (IGF-1), cyclooxygenase 3 (COX-3), adenine nucleotide translocase (ANT), and uncoupling protein 3 (UCP-3) were upregulated (p < 0.001) in M. cordata treatments with the highest value for SG50 compared with the control group. We concluded that exogenous M. cordata dietary supplementation upregulated the expression of growth-related genes in turkey at a level of 50 ppm without adverse effects on their health status regarding hematological and biochemical indices.

BackgroundThe Celastrus paniculatus (CP), commonly known as Jyotishmati, is considered as “elixir of life” by Indian people for the prevention or management of many ailments. The seed powder and its extract have widely used commercially for the preparation of various Ayurvedic formulations for the improvement of memory. CP seeds were generally extracted by conventional extraction methods (CEMs) which are assumed to impact environment burden and also produce low extract yield. Green extraction with possible improvement in extract yield has always been the need of hour for selected medicinal plant.ObjectiveIn the present research, we aimed to optimize the different extraction factors in microwave and ultrasound-based extraction. The various extracts obtained in conventional and green methods are also evaluated for the possible improvement in memory enhancing potential.Materials and MethodsThe selected medicinal herb was extracted by CEM (maceration and percolation). In green methods such microwave-assisted extraction (MAE) and ultrasound assisted-extraction (UAE), various parameters were optimized using Box-Behnken design coupled with response surface methodology. The scanning electron microscopy (SEM) and gas chromatography–mass spectroscopy (GC-MS) analyses were also done to confirm the possible improvement in concentration of plant actives. The Swiss albino mice were used to evaluate memory enhancing potential of different extracts.ResultsAt the optimized conditions MAE and UAE the extraction yield, total phenolic content (TPC) and Total flavonoid content (TFC) are significantly improved. The GC-MS analysis further confirms the improvement in concentration of certain fatty acid esters, pilocarpine, and steroidal compounds in optimized extracts. The optimized extracts also exhibited the significant improvement in behavioral parameters, oxidative stress-induced parameters, and acetylcholinesterase inhibitory potential.Discussion and ConclusionFrom the results, we can say that the application of green technologies in design-based extraction of selected herb not only significantly reduces the extraction time but also improves the extract yield and concentration of plant actives. In nutshell, it can be concluded that the green approaches for extraction of seeds of Celastrus paniculatus could be scale up at a commercial level to meet the rising demand for herbal extract.

Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes that mediate various cellular activities, including propagation, differentiation, motility, and survival. Abnormal activation of NF-κB is a common incidence in several cancers. Glioblastoma multiforme (GBM) is the most aggressive brain cancer described by high cellular heterogeneity and almost unavoidable relapse following surgery and resistance to traditional therapy. In GBM, NF-κB is abnormally activated by various stimuli. Its function has been associated with different processes, including regulation of cancer cells with stem-like phenotypes, invasion of cancer cells, and radiotherapy resistance identification of mesenchymal cells. Even though multimodal therapeutic approaches such as surgery, radiation therapy, and chemotherapeutic drugs are used for treating GBM, however; the estimated mortality rate for GBM patients is around 1 year. Therefore, it is necessary to find out new therapeutic approaches for treating GBM. Many studies are focusing on therapeutics having less adverse effects owing to the failure of conventional chemotherapy and targeted agents. Several studies of compounds suggested the involvement of NF-κB signaling pathways in the growth and development of a tumor and GBM cell apoptosis. In this review, we highlight the involvement of NF-κB signaling in the molecular understanding of GBM and natural compounds targeting NF-κB signaling.

This research was conducted to evaluate the impact of dietary or drinking water Ruminococcus sp. supplementation and/or heat stress (HS) on the growth, serum biochemistry, tissue antioxidant, phagocytic assay, histopathology, and bursa gene expression of broilers. Day-old broiler chicks were allotted into six groups according to HS and/or Ruminococcus with or without enzyme supplementation. The first group was the control one, with a formulated diet and normal environmental temperature but without any supplement. The second group fed on Ruminococcus-supplemented diet (1 kg/kg diet). The third group fed on a formulated diet without supplement, and Ruminococcus and digestive enzymes were given in drinking water (0.1 ml/L). The fourth one was the heat stress group, with a normal formulated diet. The fifth and the sixth groups served as second and third groups, respectively, but with heat stress. The results of this experiment indicated that thermal temperature negatively affected the parameters of growth performance, serum biochemical, tissue antioxidants, and phagocytic assay. Moreover, heat stress led to pathological lesions in the internal organs and affected the expression of some genes related to heat stress, including proapoptotic genes such as caspase8 and bax, inflammatory genes such as NF-κβ1, and heat shock protein such as HSP 70 in the bursal tissue. These bad effects and abnormalities were mitigated by Ruminococcus alone or with enzyme supplementation, which improved all the above-mentioned parameters.

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has a disastrous effect on mankind due to the contagious and rapid nature of its spread. Although vaccines for SARS-CoV-2 have been successfully developed, the proven, effective, and specific therapeutic molecules are yet to be identified for the treatment. The repurposing of existing drugs and recognition of new medicines are continuously in progress. Efforts are being made to single out plant-based novel therapeutic compounds. As a result, some of these biomolecules are in their testing phase. During these efforts, the whole-genome sequencing of SARS-CoV-2 has given the direction to explore the omics systems and approaches to overcome this unprecedented health challenge globally. Genome, proteome, and metagenome sequence analyses have helped identify virus nature, thereby assisting in understanding the molecular mechanism, structural understanding, and disease propagation. The multi-omics approaches offer various tools and strategies for identifying potential therapeutic biomolecules for COVID-19 and exploring the plants producing biomolecules that can be used as biopharmaceutical products. This review explores the available multi-omics approaches and their scope to investigate the therapeutic promises of plant-based biomolecules in treating SARS-CoV-2 infection.

Alzheimer’s disease (AD) is the most common form of dementia, which causes abnormalities in learning, thinking, memory, as well as behavior. Generally, symptoms of AD develop gradually and aggravate over time, and consequently severely interfere with daily activities. Furthermore, obesity is one of the common risk factors for dementia. Dysregulation of adipokine and adipocyte dysfunction are assumed to be accountable for the high risk of obesity in people that develop many related disorders such as AD. Moreover, it has been observed that the dysfunction of adipose is connected with changes in brain metabolism, brain atrophy, cognitive decline, impaired mood, neuroinflammation, impaired insulin signaling, and neuronal dysfunction in people with obesity. Conversely, the pathological mechanisms, as well as the molecular players which are involved in this association, have been unclear until now. In this article, we discuss the impact of adiponectin (AdipoQ) on obesity-related Alzheimer’s dementia.

Improving growth and productivity of plants that are vulnerable to environmental stresses, such as heavy metals, is of significant importance for meeting global food and energy demands. Because heavy metal toxicity not only causes impaired plant growth, it has also posed many concerns related to human well-being, so mitigation of heavy metal pollution is a necessary priority for a cleaner environment and healthier world. Hydrogen sulfide (H2S), a gaseous signaling molecule, is involved in metal-related oxidative stress mitigation and increased stress tolerance in plants. It performs multifunctional roles in plant growth regulation while reducing the adverse effects of abiotic stress. Most effective function of H2S in plants is to eliminate metal-related oxidative toxicity by regulating several key physiobiochemical processes. Soil pollution by heavy metals presents significant environmental challenge due to the absence of vegetation cover and the resulting depletion of key soil functions. However, the use of stress alleviators, such as H2S, along with suitable crop plants, has considerable potential for an effective management of these contaminated soils. Overall, the present review examines the imperative role of exogenous application of different H2S donors in reducing HMs toxicity, by promoting plant growth, stabilizing their physiobiochemical processes, and upregulating antioxidative metabolic activities. In addition, crosstalk of different growth regulators with endogenous H2S and their contribution to the mitigation of metal phytotoxicity have also been explored.

Alzheimer’s disease (AD) is a progressive cortex and hippocampal neurodegenerative disease which ultimately causes cognitively impaired decline in patients. The AD pathogen is a very complex process, including aggregation of Aβ (β-amyloid peptides), phosphorylation of tau-proteins, and chronic inflammation. Exactly, resveratrol, a polyphenol present in red wine, and many plants are indicated to show the neuroprotective effect on mechanisms mostly above. Resveratrol plays an important role in promotion of non-amyloidogenic cleavage of the amyloid precursor protein. It also enhances the clearance of amyloid beta-peptides and reduces the damage of neurons. Most experimental research on AD and resveratrol has been performed in many species, both in vitro and in vivo, during the last few years. Nevertheless, resveratrol’s effects are restricted by its bioavailability in the reservoir. Therefore, scientists have tried to improve its efficiency by using different methods. This review focuses on recent work done on the cell and animal cultures and also focuses on the neuroprotective molecular mechanisms of resveratrol. It also discusses about the therapeutic potential onto the treatment of AD.

Two oilseed rape genotypes (Jiu-Er-13XI and Zheyou-50), differing in seed oil content, were subjected to cadmium (Cd) stress in hydroponic experiment. Genotypic differences were observed in terms of tolerance to Cd exposure. Cd treatment negatively affected both genotypes, but the effects were more devastating in Jiu-Er-13XI (low seed oil content) than in Zheyou-50 (high seed oil content). Jiu-Er-13XI accumulated more reactive oxygen species (ROS), which destroyed chloroplast structure and decreased photosynthetic pigments, than Zheyou-50. Total fatty acids, especially 18:2 and 18:3, severely decreased as suggested by increase in MDA content. Roots and shoots of Jiu-Er-13XI plants accumulated more Cd content, while less amount of tocopherol (Toc) was observed under Cd stress, than Zheyou-50. Conversely, Zheyou-50 was less affected by Cd stress than its counterpart. It accumulated comparatively less amount of Cd in roots and shoots, along with reduced accumulation of malondialdehyde (MDA) and ROS under Cd stress, than Jiu-Er-13XI. Further, the level of Toc, especially α-Tocopherol, was much higher in Zheyou-50 than in Jiu-Er-13XI, which was also supported by high expression of Toc biosynthesis genes in Zheyou-50 during early hours. Toc not only restricted the absorption of Cd by roots and its translocation to shoot but also scavenged the ROS generated during oxidative stresses. The low level of MDA shows that polyunsaturated fatty acids in chloroplast membranes remained intact. In the present study the tolerance of Zheyou-50 to Cd stress, over Jiu-Er-13XI, is attributed to the activities of Toc. This study shows that plants with high seed oil content are tolerant to Cd stress due to high production of Toc.

At the end of 2019, a novel coronavirus (CoV) was found at the seafood market of Hubei province in Wuhan, China, and this virus was officially named coronavirus diseases 2019 (COVID-19) by World Health Organization (WHO). COVID-19 is mainly characterized by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) and creates public health concerns as well as significant threats to the economy around the world. Unfortunately, the pathogenesis of COVID-19 is unclear and there is no effective treatment of this newly life-threatening and devastating virus. Therefore, it is crucial to search for alternative methods that alleviate or inhibit the spread of COVID-19. In this review, we try to find out the etiology, epidemiology, symptoms as well as transmissions of this novel virus. We also summarize therapeutic interventions and suggest antiviral treatments, immune-enhancing candidates, general supplements, and CoV specific treatments that control replication and reproduction of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).

The recent outbreak of the COVID-2019 (coronavirus disease 2019) due to the infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has realized the requirement of alternative therapeutics to mitigate and alleviate this lethal infection. These alternative therapies are effective when they are started at the initial stage of the infection. Some drugs that were used in previous other related infections SARS-CoV-2003 and Middle East respiratory syndrome coronavirus (MERS-CoV)-2012 could be potentially active against currently emerging SARS-CoV-2. This fact imparts some rationale of current interventions, in the absence of any specific therapeutics for SARS-CoV-2. It is imperative to focus on the available antimicrobial and adjunct therapies during the current emergency state and overcome the challenges associated with the absence of robust controlled studies. There is no established set of drugs to manage SARS-CoV-2 infected patients. However, closely following patients’ conditions and responding with the dosage guidelines of available drugs may significantly impact our ability to slow down the infection. Of note, it depends upon the condition of the patients and associated comorbid; therefore, the health workers need to choose the drug combinations judiciously until COVID-19 specific drug or vaccine is developed with the collective scientific rigor. In this article, we reviewed the available antimicrobial drug, supportive therapies, and probable high importance vaccines for the COVID-19 treatment.

Chelator-assisted phytoremediation is an economical, sustainable, and ecologically friendly method of extracting heavy metals and metalloids from the soil. Organic chelators are thought to enhance metal availability and mobility in contaminated media, thereby improving phytoextraction. The aim of the present study was to examine whether exogenous application of glutamic acid (GA) could improve chromium (Cr) phytoextraction by sunflower plants (Helianthus annuus L.). Seeds were planted in plastic pots filled with 5 kg of local agricultural soil spiked with increasing concentrations of Cr (1, 2, and 5 mg kg−1). Glutamic acid (5 mM) was applied to soil in solution according to a completely randomized experimental design, and the sunflower plants were harvested after 8 weeks. The results indicated that increasing Cr-induced stress significantly inhibited plant growth, leading to reduced biomass, photosynthetic pigment content, activities of antioxidant enzymes, and leaf area of the sunflower plants. However, exogenous addition of GA significantly reduced the Cr-associated toxic effects while also increasing the accumulation of Cr in the plants. Moreover, increasing concentrations of Cr in the soil increased the generation of reactive oxygen species (ROS) responsible for the altered antioxidant enzyme activities. The results revealed that GA application to the topsoil enhanced the Cr concentration and accumulation in the root, stem, and leaves by up to 254, 225, 355, and 47, 59, 150% respectively. Further the GA addition reduced the Cr-induced toxicity in plants and might be helpful for enhancing Cr phytoextraction by sunflower plants.

Cisplatin (CP) is one of the most active medications in cancer treatment and has some adverse effects such as hepatotoxicity and nephrotoxicity. The present research was planned to determine the protective effects of L-carnitine (LC) against CP-induced hepato-renal oxidative stress in rats, via investigating of some serum biochemical and tissue oxidative/antioxidant parameters, histological alterations, and immunohistochemical expressions of two different intermediate filaments (IFs) proteins; vimentin (VIM) and cytokeratin 18 (CK18). Twenty-eight rats were divided into four groups (7 rats each). Groups I and II were orally administered saline and LC (100 mg/kg body weight), respectively, once daily for 30 consecutive days. Group III received saline orally once daily and a single dose of CP on the 27th day of the experiment [7.5 mg/kg, intraperitoneal (IP)]. Group IV received both LC and CP. Injection of CP significantly (P ≤ 0.05) increased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities and creatinine and urea levels, while serum total protein, albumin, and globulin concentrations significantly (P ≤ 0.05) decreased. In addition, CP induced a dramatic increase in the Malondialdehyde (MDA) level along with a substantial decrease in reduced glutathione (GSH) and catalase (CAT) in the hepato-renal tissues. Histologically, both liver and kidney of the CP treated group revealed marked degenerative changes. Moreover, overexpression of both VIM and CK18 in hepato-renal tissues were noted after CP injection. On the other hand, the administration of LC in the CP injected group (Group IV) restored the biochemical parameters, histological, and immunohistochemical pictures toward the normalcy. In conclusion, LC may be supplemented for chemotherapy with CP to ameliorate its oxidative stress and restore the normal organization of IFs, especially VIM and CK18 within the CP intoxicated hepato-renal cells.

Alzheimer’s disease (AD) is an irreversible chronic neurodegenerative disorder that occurs when neurons in the brain degenerate and die. Pain frequently arises in older patients with neurodegenerative diseases including AD. However, the presence of pain in older people is usually overlooked with cognitive dysfunctions. Most of the times dementia patients experience moderate to severe pain but the development of severe cognitive dysfunctions tremendously affects their capability to express the presence of pain. Currently, there are no effective treatments against AD that emphasize the necessity for increasing research to develop novel drugs for treating or preventing the disease process. Furthermore, the prospective therapeutic use of cannabinoids in AD has been studied for the past few years. In this regard, targeting the endocannabinoid system has considered as a probable therapeutic strategy to control several associated pathological pathways, such as mitochondrial dysfunction, excitotoxicity, oxidative stress, and neuroinflammation for the management of AD. In this review, we focus on recent studies about the role of cannabinoids for the treatment of pain and related neuropathological changes in AD.

In December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related epidemic was first observed in Wuhan, China. In 2020, owing to the highly infectious and deadly nature of the virus, this widespread novel coronavirus disease 2019 (nCOVID-19) became a worldwide pandemic. Studies have revealed that various environmental factors including temperature, humidity, and air pollution may also affect the transmission pattern of COVID-19. Unfortunately, still, there is no specific drug that has been validated in large-scale studies to treat patients with confirmed nCOVID-19. However, remdesivir, an inhibitor of RNA-dependent RNA polymerase (RdRp), has appeared as an auspicious antiviral drug. Currently, a large-scale study on remdesivir (i.e., 200 mg on first day, then 100 mg once/day) is ongoing to evaluate its clinical efficacy to treat nCOVID-19. Good antiviral activity against SARS-CoV-2 was not observed with the use of lopinavir/ritonavir (LPV/r). Nonetheless, the combination of umifenovir and LPV/r was found to have better antiviral activity. Furthermore, a combination of hydroxychloroquine (i.e., 200 mg 3 times/day) and azithromycin (i.e., 500 mg on first day, then 250 mg/day from day 2–5) also exhibited good activity. Currently, there are also ongoing studies to evaluate the efficacy of teicoplanin and monoclonal and polyclonal antibodies against SARS-CoV-2. Thus, in this article, we have analyzed the genetic diversity and molecular pathogenesis of nCOVID-19. We also present possible therapeutic options for nCOVID-19 patients.

Neuropathic pain (NP) is the result of irregular processing in the central or peripheral nervous system, which is generally caused by neuronal injury. The management of NP represents a great challenge owing to its heterogeneous profile and the significant undesirable side effects of the frequently prescribed psychoactive agents, including benzodiazepines (BDZ). Currently, several established drugs including antidepressants, anticonvulsants, topical lidocaine, and opioids are used to treat NP, but they exert a wide range of adverse effects. To reduce the burden of adverse effects, we need to investigate alternative therapeutics for the management of NP. Flavonoids are the most common secondary metabolites of plants used in folkloric medicine as tranquilizers, and have been claimed to have a selective affinity to the BDZ binding site. Several studies in animal models have reported that flavonoids can reduce NP. In this paper, we emphasize the potentiality of flavonoids for the management of NP.

Feed additives are used frequently in variable combinations to maximize broiler productivity and consumer safety. Therefore, we evaluated the efficiency of feed additives used in four different diets: a basal diet, a probiotic (PRO-PAC®) supplement diet, an egg yolk purified immunoglobulin Y (IgY) supplemented diet, and a combination of IgY and PRO-PAC® supplement (n = 15 for each group). We assessed the improvement of behavioral and hematological parameters of Ross broilers before and after an immune stress challenge using lipopolysaccharide (LPS). Behavioral as well as physiological parameters were analyzed. The standing frequency was the highest (P < 0.05) in broilers supplemented with a combination of probiotics and IgY. Likewise, latency approach score to a novel object improved (P < 0.01) in the combination group at week-3. After intraperitoneal injection of LPS, this combination group achieved the best gait score at week-3, followed by week-5, compared to birds fed the basal diet. The heterophil/lymphocyte (H/L) ratio, heterophil differential count, and eosinophil differential count in the basal diet group that was challenged with LPS were significantly increased (P < 0.01, P < 0.001, P < 0.05, respectively) compared to the combination groups. Therefore, we concluded that the combination of IgY and probiotics can significantly improve the behavior and the underlying physiological parameters of Ross broilers. Consequently, this combination can improve the broilers′ health, welfare and produce a safe meat free from harmful chemical residues.

Over the past decades, researchers have reported several mechanisms for doxorubicin (DOX)-induced cardiomyopathy, including oxidative stress, inflammation, and apoptosis. Another mechanism that has been suggested is that DOX interferes with the cell cycle and induces oxidative stress in C-kit+ cells (commonly known as cardiac progenitor cells), reducing their regenerative capacity. Cardiac regeneration through enhancing the regenerative capacity of these cells or administration of other stem cells types has been the axis of several studies over the past 20 years. Several experiments revealed that local or systemic injections with mesenchymal stem cells (MSCs) were associated with significantly improved cardiac function, ameliorated inflammatory response, and reduced myocardial fibrosis. They also showed that several factors can affect the outcome of MSC treatment for DOX cardiomyopathy, including the MSC type, dose, route, and timing of administration. However, there is growing evidence that the C-kit+ cells do not have a cardiac regenerative potential in the adult mammalian heart. Similarly, the protective mechanisms of MSCs against DOX-induced cardiomyopathy are not likely to include direct differentiation into cardiomyocytes and probably occur through paracrine secretion, antioxidant and anti-inflammatory effects. Better understanding of the involved mechanisms and the factors governing the outcomes of MSCs therapy are essential before moving to clinical application in patients with DOX-induced cardiomyopathy.

This study was performed to compare the nephroprotective effects of benzyl isothiocyanate (BITC) and resveratrol (RES) and investigate the nephroprotective efficacy of their combination against cisplatin-induced acute renal injury. Five animal groups (each of eight) received either normal saline, a single intraperitoneal injection of cisplatin (20 mg/kg) at the sixth day, cisplatin plus oral RES (30 mg/kg) or BITC (100 mg/kg in diet), or a combination of both for 10 days. Compared to saline-treated mice, cisplatin-intoxicated mice had significantly higher (p < 0.05) serum levels of urea, creatinine, interleukin-1β (IL-1β), and tumor necrosis factor-α. Moreover, biochemical analysis of kidney tissue homogenates showed that cisplatin intoxication was associated with significantly higher (p < 0.05) tissue levels of malondialdehyde (MDA) and lower levels of reduced glutathione and activities of endogenous antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) in comparison to normal controls. Histopathological and immunohistochemical examinations of renal tissue slices from cisplatin-intoxicated mice showed interstitial leukocytic infiltration, tortuous tubules with vacuolated epithelium, luminal casts, and overexpression of cyclooxygenase-II enzyme. On the other hand, treatment with RES or BITC ameliorated all the previous parameters. The effects of both compounds were comparable in all assessed parameters, except IL-1β serum concentration and renal tissue MDA concentration (which were significantly lower in the RES group). Interestingly, treatment with BITC and RES combination restored the normal concentrations of all the aforementioned biochemical parameters, as well as near normal histological and immunohistochemical pictures. In conclusion, BITC exerted nearly comparable nephroprotective, antioxidant, and anti-inflammatory effects to RES and the combination of both agents showed more potent nephroprotective effects against cisplatin than each one alone.

Alzheimer’s disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.