APLpred: A machine learning-based tool for accurate prediction and characterization of asparagine peptide lyases using sequence-derived optimal features.

Asparagine peptide lyase (APL) is among the seven groups of proteases, also known as proteolytic enzymes, which are classified according to their catalytic residue. APLs are synthesized as precursors or propeptides that undergo self-cleavage through autoproteolytic reaction. At present, APLs are grouped into 10 families belonging to six different clans of proteases. Recognizing their critical roles in many biological processes including virus maturation, and virulence, accurate identification and characterization of APLs is indispensable. Experimental identification and characterization of APLs is laborious and time-consuming. Here, we developed APLpred, a novel support vector machine (SVM) based predictor that can predict APLs from the primary sequences. APLpred was developed using Boruta-based optimal features derived from seven encodings and subsequently trained using five machine learning algorithms. After evaluating each model on an independent dataset, we selected APLpred (an SVM-based model) due to its consistent performance during cross-validation and independent evaluation. We anticipate APLpred will be an effective tool for identifying APLs. This could aid in designing inhibitors against these enzymes and exploring their functions. The APLpred web server is freely available at https://procarb.org/APLpred/.

Screening, awareness and challenges for colorectal cancer treatment in Saudi Arabia: an update.

Colorectal cancer (CRC) is the second most common cancer in the world. In Saudi Arabia, CRC is the most common cancer in males and the third most common in females, and its incidence rate is rising as the country continues to develop. However, the country does not have a national CRC screening program for CRC. This review aims to review recent studies that have attempted to address and rectify this issue and discern the most notable and prevalent barriers. Despite these efforts, guidelines are still lacking. Two prospective studies have been conducted in recent years, one of which was a national pilot screening program conducted by the Ministry of Health (MOH). While both had a similar number of participants, the colonoscopy rate for patients with a positive fecal immunochemical test (FIT) in the MOH program was only 20% compared to 75.8% in the Al-Kharj program. Awareness of the Saudi population regarding CRC and its screening appears to be insufficient. The most common barriers to patients' willingness to undergo screening were embarrassment, fear, and pain. Barriers to physicians are mostly related to factors outside their hands, such as lack of equipment and time. We conclude that efforts should be made to establish a national screening program and improve awareness of the population and physicians.

Efficacy of Probiotic Strains Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 in Management of Obesity: An In Vitro and In Vivo Analysis.

The prevalence of obesity, characterized by an excessive accumulation of adipose tissue and adipocyte hypertrophy, presents a major public health challenge. This study investigates the therapeutic potential of two probiotic strains, Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093, in the context of obesity. Utilizing 3T3-L1 cell-derived human adipocytes, we assessed Probio65's and Probio-093's capacity to mitigate triglyceride accumulation and influence adipocytokine production in vitro. Subsequently, an in vivo trial with male C57BL/6J mice examined the effects of both probiotic strains on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. This study employed both live and ethanol-extracted bacterial cells. The results demonstrated significant reductions in the triglyceride deposition, body weight, and adipose tissue mass in the treated groups (p < 0.05). Furthermore, both strains modulated adipokine profiles by downregulating proinflammatory markers such as PAI-1, leptin, TNF-α, STAMP2, F4/80, resistin, and MCP-1, and upregulating the insulin-sensitive transporter GLUT4 and the anti-inflammatory adiponectin (p < 0.05). Our findings suggest that Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 are promising agents for microbiome-targeted anti-obesity therapies, offering the effective mitigation of obesity and improvement in adipocyte function in a murine model.

Role of ribosomal pathways and comorbidity in COVID-19: Insight from SARS-CoV-2 proteins and host proteins interaction network analysis.

The COVID-19 pandemic has become a significant global issue in terms of public health. While it is largely associated with respiratory complications, recent reports indicate that patients also experience neurological symptoms and other health issues. The objective of this study is to examine the network of protein-protein interactions (PPI) between SARS-CoV-2 proteins and human host proteins, pinpoint the central genes within this network implicated in disease pathology, and assess their viability as targets for drug development. The study adopts a network-based approach to construct a network of 29 SARS-CoV-2 proteins interacting with 2896 host proteins, with 176 host genes being identified as interacting genes with all the viral proteins. Gene ontology and pathway analysis of these host proteins revealed their role in biological processes such as translation, mRNA splicing, and ribosomal pathways. We further identified EEF2, RPS3, RPL9, RPS16, and RPL11 as the top 5 most connected hub genes in the disease-causing network, with significant interactions among each other. These hub genes were found to be involved in ribosomal pathways and cytoplasmic translation. Further a disease-gene interaction was also prepared to investigate the role of hub genes in other disorders and to understand the condition of comorbidity in COVID-19 patients. We also identified 13 drug molecules having interactions with all the hub genes, and estradiol emerged as the top potential drug target for the COVID-19 patients. Our study provides valuable insights using the protein-protein interaction network of SARS-CoV-2 proteins with host proteins and highlights the molecular basis of manifestation of COVID-19 and proposes drug for repurposing. As the pandemic continues to evolve, it is anticipated that investigating SARS-CoV-2 proteins will remain a critical area of focus for researchers globally, particularly in addressing potential challenges posed by specific SARS-CoV-2 variants in the future.

3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study's objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

Sugiol Masters Apoptotic Precision to Halt Gastric Cancer Cell Proliferation.

Sugiol, a natural compound with anticancer properties, has shown promise in various cancer types, but its potential in preventing gastric cancer remains uncertain. In this study, we aimed to examine the inhibitory effect of sugiol on human gastric cancer cell proliferation. Our findings demonstrate that sugiol effectively suppresses the proliferation of SNU-5 human gastric cancer cells, leading to apoptotic cell death. We assessed the chemo-preventive potential of sugiol via an MTT assay and confirmed the induction of oxidative stress using the H2DCFDA fluorescent dye. Treatment with sugiol at concentrations higher than 25 µM for 24 h resulted in an increase in intracellular levels of reactive oxygen species (ROS). This elevation of ROS levels inhibited cell-cycle progression and induced cell-cycle arrest at the G1 phase. Furthermore, our study revealed that sugiol reduces the viability and proliferation of SNU-5 cells in a dose-dependent manner. Importantly, ADME and toxicity analyses revealed that sugiol was effective and nontoxic at low doses. In parallel, we utilized the Swiss target prediction tool to identify potential targets for sugiol. Enzymes and nuclear receptors were identified as major targets. To gain insights into the molecular interactions, we performed structure-based molecular docking studies, focusing on the interaction between sugiol and STAT3. The docking results revealed strong binding interactions within the active site pocket of STAT3, with a binding affinity of -12.169 kcal/mole. Sugiol's -OH group, carbonyl group, and phenyl ring demonstrated hydrogen-bonding interactions with specific residues of the target protein, along with Vander Waals and hydrophobic interactions. These data suggest that sugiol has the potential to inhibit the phosphorylation of STAT3, which is known to play a crucial role in promoting the growth and survival of cancer cells. Targeting the dysregulated STAT3 signaling pathway holds promise as a therapeutic strategy for various human tumors. In combination with interventions that regulate cell cycle progression and mitigate the DNA damage response, the efficacy of these therapeutic approaches can be further enhanced. The findings from our study highlight the antiproliferative and apoptotic potential of sugiol against human gastric cancer cells (SNU-5). Moreover, the result underpins that sugiol's interactions with STAT3 may contribute to its inhibitory effects on cancer cell growth and proliferation. Further research is warranted to explore the full potential of sugiol as a therapeutic agent and its potential application in treating gastric cancer and other malignancies characterized by dysregulated STAT3 activity.

Assessing Spectral Analysis of Phytoconstituents and Their In Silico Interactions with Target Proteins in Plant Seed Extracts.

The pharmacological and preventive attributes of extracts from vegetable seeds have garnered widespread recognition within the scientific community. This study systematically assessed the in vitro antibacterial, antioxidant, and anti-breast cancer properties of phytochemicals present in various solvent-based vegetable seed extracts. We also conducted molecular docking simulations to ascertain their interactions with specific target proteins. Besides, nine distinct chemical constituents were identified using gas chromatography-mass spectrometry (GCMS). Remarkably, the ethyl acetate extract exhibited robust inhibitory effects against Gram-positive and Gram-negative bacterial strains. Furthermore, its capacity for 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging was found to be noteworthy, with an IC50 value of 550.82 ± 1.7 µg/mL, representing a scavenging efficiency of 64.1 ± 2.8%. Additionally, the ethyl acetate extract demonstrated significant hydrogen peroxide (H2O2) scavenging activity, with a maximal scavenging rate of 44.1 ± 1.70% (IC50) at a concentration of 761.17 ± 1.8 µg/mL. Intriguingly, in vitro cytotoxicity assays against human breast cancer (MCF-7) cells revealed varying levels of cell viability at different extract concentrations, suggesting potential anticancer properties. Importantly, these ethyl acetate extracts did not display toxicity to L929 cells across the concentration range tested. Subsequently, we conducted in-silico molecular docking experiments utilizing Discovery Studio 4.0 against the c-Met kinase protein (hepatocyte growth factor; PDB ID: 1N0W). Among the various compounds assessed, 3,4-Dihydroxy-1,6-bis-(3-methoxy-phenyl)-hexa-2,4-diene-1,6-dione exhibited a notable binding energy of -9.1 kcal/mol, warranting further investigation into its potential anticancer properties, clinical applications, and broader pharmacological characteristics.

Pr3+ Ion-Substituted Ni-Co Nano-Spinel Ferrites: Their Synthesis, Characterization, and Biocompatibility for Colorectal Cancer and Candidaemia.

Nanotherapeutics have attracted tremendous research interest in the modern pharmaceutical and biomedical industries due to their potential for drug development, targeted delivery, and therapeutic applications. Therefore, the current study underpins the synthesis of praseodymium ion (Pr3+)-substituted Ni0.5Co0.5Fe2O4 nano-spinel ferrites, (Co0.5Ni0.5PrxFe2-xO4 (0.0 ≤ x ≤ 0.10) NSFs, CoNiPr (x ≤ 0.10) NSFs) via the sonochemical route for its application as a nanotherapeutic treatment option. The synthesized nanomaterial was characterized using various analytical techniques, including scanning/transmission electron microscopy (SEM) and X-ray powder diffractometry (XRD). After substitution with Pr (x = 0.08), the particle size, polydispersity index, and zeta potential analysis indicated an increase in hydrodynamic diameter, with an average zeta potential value of -10.2 mV. The investigation of CoNiPr (x ≤ 0.10) NSFs on colorectal cancer (HCT-116) cells demonstrated a significant effect on cancer cell viability. The inhibitory concentration (IC50) of CoNiPr (x ≤ 0.10) NSFs was between 46 ± 0.91 and 288 ± 8.21 for HCT-116 cells. The effect of CoNiPr (x ≤ 0.10) NSFs on normal human embryonic kidney (HEK-293) cells showed a reduction in the HEK-293 cell viability; however, the cell viability was better than HCT-116. The NSFs treatment also showed morphological changes in cancer cell nuclei, as revealed by DAPI (4',6-diamidino-2-phenylindole), nuclear disintegration, and chromatic fragmentation, which are signs of apoptosis or programmed cell death. To examine the potential antifungal effects of CoNiPr NSFs on Candida albicans, known to cause candidemia among cancer patients, the viability of the cells was assessed post treatment with CoNiPr (x ≤ 0.10) NSFs. The increasing ratio of dopant had a moderate impact on the percentage of cell viability loss of 42, 44, and 43% with x = 0.06, 0.08, and 0.10, respectively. These results reinforce that increased dopant significantly impacts the antifungal properties of the synthesized nanomaterial. These findings support the idea that NSFs might be useful in pharmaceuticals.

Plant beneficial microbiome a boon for improving multiple stress tolerance in plants.

Beneficial microbes or their products have been key drivers for improving adaptive and growth features in plants under biotic and abiotic stress conditions. However, the majority of these studies so far have been utilized against individual stressors. In comparison to individual stressors, the combination of many environmental stresses that plants experience has a greater detrimental effect on them and poses a threat to their existence. Therefore, there is a need to explore the beneficial microbiota against combined stressors or multiple stressors, as this will offer new possibilities for improving plant growth and multiple adaptive traits. However, recognition of the multifaceted core beneficial microbiota from plant microbiome under stress combinations will require a thorough understanding of the functional and mechanistic facets of plant microbiome interactions under different environmental conditions in addition to agronomic management practices. Also, the development of tailored beneficial multiple stress tolerant microbiota in sustainable agriculture necessitates new model systems and prioritizes agricultural microbiome research. In this review, we provided an update on the effect of combined stressors on plants and their microbiome structure. Next, we discussed the role of beneficial microbes in plant growth promotion and stress adaptation. We also discussed how plant-beneficial microbes can be utilized for mitigating multiple stresses in plants. Finally, we have highlighted some key points that warrant future investigation for exploring plant microbiome interactions under multiple stressors.

Nano-sized warriors: zinc chromium vanadate nanoparticles as a dual solution for eradicating waterborne enterobacteriaceae and fighting cancer.

The revolution of biomedical applications has opened new avenues for nanotechnology. Zinc Chromium vanadate nanoparticles (VCrZnO4 NPs) have emerged as an up-and-coming candidate, with their exceptional physical and chemical properties setting them apart. In this study, a one-pot solvothermal method was employed to synthesize VCrZnO4 NPs, followed by a comprehensive structural and morphological analysis using a variety of techniques, including X-Ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, Energy-dispersive X-ray, and X-ray photoelectron spectroscopy. These techniques confirmed the crystallinity of the NPs. The VCrZnO4 NPs were tested for their antibacterial activity against primary contaminants such as Enterobacteriaceae, including Shigella flexneri, Salmonella cholerasis, and Escherichia coli, commonly found in hospital settings, using the broth dilution technique. The results indicated a stronger antibacterial activity of VCrZnO4 NPs against Shigella and Salmonella than E. coli. Electron microscopy showed that the NPs caused severe damage to the bacterial cell wall and membrane, leading to cell death. In addition, the study evaluated the anticancer activities of the metal complexes in vitro using colorectal cancer cells (HCT-116) and cervical cancer cells (HELA), along with non-cancer cells and human embryonic kidney cells (HEK-293). A vanadium complex demonstrated efficient anticancer effects with half-inhibitory concentrations (IC50) of 38.50+3.50 g/mL for HCT-116 cells and 42.25+4.15 g/mL for HELA cells. This study highlights the potential of Zinc Chromium vanadate nanoparticles as promising candidates for antibacterial and anticancer applications. Various advanced characterization techniques were used to analyze the properties of nanomaterials, which may help develop more effective and safer antibacterial and anticancer agents in the future.

The gut dysbiosis-cancer axis: illuminating novel insights and implications for clinical practice.

The human intestinal microbiota, also known as the gut microbiota, comprises more than 100 trillion organisms, mainly bacteria. This number exceeds the host body cells by a factor of ten. The gastrointestinal tract, which houses 60%-80% of the host's immune cells, is one of the largest immune organs. It maintains systemic immune homeostasis in the face of constant bacterial challenges. The gut microbiota has evolved with the host, and its symbiotic state with the host's gut epithelium is a testament to this co-evolution. However, certain microbial subpopulations may expand during pathological interventions, disrupting the delicate species-level microbial equilibrium and triggering inflammation and tumorigenesis. This review highlights the impact of gut microbiota dysbiosis on the development and progression of certain types of cancers and discusses the potential for developing new therapeutic strategies against cancer by manipulating the gut microbiota. By interacting with the host microbiota, we may be able to enhance the effectiveness of anticancer therapies and open new avenues for improving patient outcomes.

Limosilactobacillus fermentum KAU0021 Abrogates Mono- and Polymicrobial Biofilms Formed by Candida albicans and Staphylococcus aureus.

Candida albicans and Staphylococcus aureus, representing two different kingdoms, are the most frequently isolated pathogens from invasive infections. Their pathogenic attributes, combined with drug resistance, make them a major threat and a challenge to successful treatments, mainly when involved in polymicrobial biofilm-associated infections. In the present study, we investigated the antimicrobial potential of Lactobacillus metabolite extracts (LMEs) purified from cell-free supernatant of four Lactobacillus strains (KAU007, KAU0010, KAU0021, and Pro-65). Furthermore, LME obtained from the strain KAU0021 (LMEKAU0021), being the most effective, was analyzed for its anti-biofilm property against mono- and polymicrobial biofilms formed by C. albicans and S. aureus. The impact of LMEKAU0021 on membrane integrity in single and mixed culture conditions was also evaluated using propidium iodide. The MIC values recorded for LMEKAU0021 was 406 µg/mL, 203 µg/mL, and 406 µg/mL against planktonic cells of C. albicans SC5314, S. aureus and polymicrobial culture, respectively. The LMEKAU0021 at sub-MIC values potentially abrogates both biofilm formation as well as 24 h mature mono- and polymicrobial biofilms. These results were further validated using different microscopy and viability assays. For insight mechanism, LMEKAU0021 displayed a strong impact on cell membrane integrity of both pathogens in single and mixed conditions. A hemolytic assay using horse blood cells at different concentrations of LMEKAU0021 confirmed the safety of this extract. The results from this study correlate the antimicrobial and anti-biofilm properties of lactobacilli against bacterial and fungal pathogens in different conditions. Further in vitro and in vivo studies determining these effects will support the aim of discovering an alternative strategy for combating serious polymicrobial infections caused by C. albicans and S. aureus.

Reversal of Azole Resistance in Candida albicans by Human Neutrophil Peptide.

With the spread of AIDS and the increase in immunocompromised patients, multi-drug-resistant fungal infections have become a serious concern among clinicians, predominantly in the developing world. Therefore, developing novel strategies and new drugs is essential to overcome drug resistance in fungal pathogens. Antimicrobial peptides of human origin have been investigated as a potential treatment against Candida infections. In this study, human neutrophil peptide (HNP) was tested for its antifungal activity alone and in combination with fluconazole (FLC) against azole-susceptible and resistant C. albicans isolates, following CLSI guidelines. Susceptibility and combination interactions were also confirmed by MUSE cell viability assay and isobolograms for synergistic combinations, respectively. The effect of HNP on biofilm inhibition was determined spectrophotometrically and microscopically. Drug susceptibility testing showed minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) ranging from 7.813 to 62.5 µg/mL and 15.625 to 250 µg/mL against all the tested C. albicans strains. The combination activity of FLC with HNP exhibited synergistic and additive interactions in 43% of each and indifferent interaction in 14%, and none of the combinations showed antagonistic interaction. Furthermore, HNB inhibited biofilm formation in all the tested C. albicans isolates. At the respective MICs, HNP exhibited inhibitory effects on the activity of the drug efflux pumps and their genes. These results warrant the application of HNP as a mono- or combination therapy with FLC to treat azole-resistant C. albicans.

Lactiplantibacillus plantarum KAU007 Extract Modulates Critical Virulence Attributes and Biofilm Formation in Sinusitis Causing Streptococcus pyogenes.

Streptococcus pyogenes is one of the most common bacteria causing sinusitis in children and adult patients. Probiotics are known to cause antagonistic effects on S. pyogenes growth and biofilm formation. In the present study, we demonstrated the anti-biofilm and anti-virulence properties of Lactiplantibacillus plantarum KAU007 against S. pyogenes ATCC 8668. The antibacterial potential of L. plantarum KAU007 metabolite extract (LME) purified from the cell-free supernatant of L. plantarum KAU007 was evaluated in terms of minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). LME was further analyzed for its anti-biofilm potential using crystal violet assay and microscopic examination. Furthermore, the effect of LME was tested on the important virulence attributes of S. pyogenes, such as secreted protease production, hemolysis, extracellular polymeric substance production, and cell surface hydrophobicity. Additionally, the impact of LME on the expression of genes associated with biofilm formation and virulence attributes was analyzed using qPCR. The results revealed that LME significantly inhibited the growth and survival of S. pyogenes at a low concentration (MIC, 9.76 µg/mL; MBC, 39.06 µg/mL). Furthermore, LME inhibited biofilm formation and mitigated the production of extracellular polymeric substance at a concentration of 4.88 µg/mL in S. pyogenes. The results obtained from qPCR and biochemical assays advocated that LME suppresses the expression of various critical virulence-associated genes, which correspondingly affect various pathogenicity markers and were responsible for the impairment of virulence and biofilm formation in S. pyogenes. The non-hemolytic nature of LME and its anti-biofilm and anti-virulence properties against S. pyogenes invoke further investigation to study the role of LME as an antibacterial agent to combat streptococcal infections.

The Inhibition of SARS-CoV-2 and the Modulation of Inflammatory Responses by the Extract of Lactobacillus sakei Probio65.

In the three years since the first outbreak of COVID-19 in 2019, the SARS-CoV-2 virus has continued to be prevalent in our community. It is believed that the virus will remain present, and be transmitted at a predictable rate, turning endemic. A major challenge that leads to this is the constant yet rapid mutation of the virus, which has rendered vaccination and current treatments less effective. In this study, the Lactobacillus sakei Probio65 extract (P65-CFS) was tested for its safety and efficacy in inhibiting SARS-CoV-2 replication. Viral load quantification by RT-PCR showed that the P65-CFS inhibited SARS-CoV-2 replication in human embryonic kidney (HEK) 293 cells in a dose-dependent manner, with 150 mg/mL being the most effective concentration (60.16% replication inhibition) (p < 0.05). No cytotoxicity was inflicted on the HEK 293 cells, human corneal epithelial (HCE) cells, or human cervical (HeLa) cells, as confirmed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The P65-CFS (150 mg/mL) also reduced 83.40% of reactive oxidizing species (ROS) and extracellular signal-regulated kinases (ERK) phosphorylation in virus-infected cells, both of which function as important biomarkers for the pathogenesis of SARS-CoV-2. Furthermore, inflammatory markers, including interferon-α (IFN-α), IFN-ß, and interleukin-6 (IL-6), were all downregulated by P65-CFS in virus-infected cells as compared to the untreated control (p < 0.05). It was conclusively found that L. sakei Probio65 showed notable therapeutic efficacy in vitro by controlling not only viral multiplication but also pathogenicity; this finding suggests its potential to prevent severe COVID-19 and shorten the duration of infectiousness, thus proving useful as an adjuvant along with the currently available treatments.

A Subtraction Genomics-Based Approach to Identify and Characterize New Drug Targets in Bordetella pertussis: Whooping Cough.

Bordetella pertussis is a Gram-negative bacterium known to cause pertussis or whooping cough. The disease affects the respiratory system and is contagious. Pertussis causes high mortality among infants aged less than one-year-old, although it can affect anyone of any age. Globally, 16 million cases of pertussis were reported in 2008, 95% of which were in developing nations, and approximately 195,000 children died from the disease. Under a computational subtractive genomics approach, the total proteome of a pathogen is gently trimmed down to a few potential drug targets. First, from NCBI, we obtained the pathogen proteins followed by CD hit for removal of duplicate proteins. The BLAST step was applied to find non-similar proteins, and then, we applied BLAST to these non-similar bacterial proteins with DEG to find essential bacterial proteins. After this, to find the location, these vital proteins were screened via PSORTb; the majority of proteins were in cytoplasm. The KASS server was used to determine the involvement of these proteins in the metabolic pathways of bacteria, and KEGG was applied to find the unique metabolic pathways of the pathogen. Finally, we applied BLAST to these vital, unique, and non-similar proteins with FDA-approved drug targets, and four proteins of the B. pertussis strain B1917 were identified that might be powerful drug targets. A variety of therapeutic molecules could be designed to target these proteins in order to treat infections caused by bacteria.

Evaluation of Lactiplantibacillus plantarum KAU007 against Low-Pathogenic Avian Influenza Virus (H9N2).

Avian influenza A viruses (AIVs) pose a persistent threat to humans owing to their reassortment and antigenic drift properties. Among them is H9N2, a low-pathogenic avian influenza virus first discovered in the non-human host and later found infective to humans with huge pandemic potential. In recent years, antiviral resistance has become an increasing threat to public health. Additionally, vaccination against AIVs is becoming increasingly challenging with little success due to antigenic drift. This has resulted in a growing demand for products that can replace the presently in-use medications and the development of innovative antiviral therapies. In this study, we systematically investigate the antiviral potential of lactic acid bacteria against H9N2. Bacteria that produce lactic acid are commonly used in food processing. In addition, these bacteria are considered more affordable, effective, and safe "nutraceuticals" than other alternative medicines. We tested Lactiplantibacillus plantarum KAU007 against the low-pathogenic avian influenza virus (H9N2). As confirmed by the hemagglutination assay, KAU007 showed potent antiviral activity against H9N2 and vigorous antioxidant activity. The CFCS showed a dose-dependent reduction in the levels of IL-6 and IFN-γ. Thus, KAU007 might be considered a potential H9N2 target-based probiotic.

In Vitro Evaluation of Leuconostoc mesenteroides Cell-Free-Supernatant GBUT-21 against SARS-CoV-2.

The unprecedented health catastrophe derived from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 infection) met with a phenomenal scientific response across the globe. Worldwide, the scientific community was focused on finding a cure for the deadly disease. A wide range of research studies has consistently revealed the link between SARS-CoV-2 infection severity and abnormal gut microbiomes, suggesting its potential in developing novel therapeutic approaches. Probiotics have been extensively studied to promote health in human hosts and reestablish a balance in the dysbiotic gut microbiome; however, there is strong skepticism about their safety and efficacy. Consequently, the metabolic signatures of probiotics, often referred to as "postbiotics", could prove of paramount importance for adjuvant cures in patients with SARS-CoV-2. Postbiotics exhibit safety, enhanced shelf-life, and stability and, therefore, could be implemented in SARS-CoV-2 prophylactic strategies with no undue adverse side effects. The current study is a preliminary investigation of the antiviral properties of postbiotic metabolites derived from Leuconostoc mesenteroides GBUT-21. The study focuses on the potential biological role in inactivating SARS-CoV-2 and reducing related inflammatory pathways.

Insights into the biodegradation and heavy metal resistance potential of the genus Brevibacillus through comparative genome analyses.

Members of the genus Brevibacillus belonging to the familyPaenibacillaceae are Gram-positive/variable, endospore-forming, and rod-shaped bacteria that dwell in various environmental habitats. Brevibacillus spp. have a wide range of enzyme activities such as degradation of various carbohydrates, plastics, and they possess resistance against heavy metals. These characteristics make them encouraging contenders for biotechnological applications.In this work, we analyzed the reference genomes of 19Brevibacillusspecies, focusing on discovering the biodegradation and heavy metal resistance capabilities of this little studied genus from genomic data. The results indicate that several strain specific traits were identified. For example Brevibacillus halotolerans s-14, and Brevibacillus laterosporus DSM 25 have more glycoside hydrolases (GHs) compared to other carbohydrate-active enzymes, and therefore might be more suitable for biodegradation of carbohydrates. In contrast, strains such as Brevibacillus antibioticus TGS2-1, with a higher number of glycosyltransfereases (GTs) may aid in the biosynthesis of complex carbohydrates. Our results also suggest some correlation between heavy metal resistance and polyurethane degradation, thus indicating that heavy metal resistance strains (e.g. Brevibacillus reuszeri J31TS6) can be a promising source of enzymes for polyurethane degradation. These strain specific features make the members of this bacterial group potential candidates for further investigations with industrial implications. This work also represents the first exhaustive study of Brevibacillus at the genome scale.

Z-Guggulsterone Is a Potential Lead Molecule of Dawa-ul-Kurkum against Hepatocellular Carcinoma.

An ancient saffron-based polyherbal formulation, Dawa-ul-Kurkum (DuK), has been used to treat liver ailments and other diseases and was recently evaluated for its anticancer potential against hepatocellular carcinoma (HCC) by our research team. To gain further insight into the lead molecule of DuK, we selected ten active constituents belonging to its seven herbal constituents (crocin, crocetin, safranal, jatamansone, isovaleric acid, cinnamaldehyde, coumaric acid, citral, guggulsterone and dehydrocostus lactone). We docked them with 32 prominent proteins that play important roles in the development, progression and suppression of HCC and those involved in endoplasmic reticulum (ER) stress to identify the binding interactions between them. Three reference drugs for HCC (sorafenib, regorafenib, and nivolumab) were also examined for comparison. The in silico studies revealed that, out of the ten compounds, three of them-viz., Z-guggulsterone, dehydrocostus lactone and crocin-showed good binding efficiency with the HCC and ER stress proteins. Comparison of binding affinity with standard drugs was followed by preliminary in vitro screening of these selected compounds in human liver cancer cell lines. The results provided the basis for selecting Z-guggulsterone as the best-acting phytoconstituent amongst the 10 studied. Further validation of the binding efficiency of Z-guggulsterone was undertaking using molecular dynamics (MD) simulation studies. The effects of Z-guggulsterone on clone formation and cell cycle progression were also assessed. The anti-oxidant potential of Z-guggulsterone was analyzed through DPPH and FRAP assays. qRTPCR was utilized to check the results at the in vitro level. These results indicate that Z-guggulsterone should be considered as the main constituent of DuK instead of the crocin in saffron, as previously hypothesized.