Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder.

The salient features of autism spectrum disorder (ASD) encompass persistent difficulties in social communication, as well as the presence of restricted and repetitive facets of behavior, hobbies, or pursuits, which are often accompanied with cognitive limitations. Over the past few decades, a sizable number of studies have been conducted to enhance our understanding of the pathophysiology of ASD. Preclinical rat models have proven to be extremely valuable in simulating and analyzing the roles of a wide range of established environmental and genetic factors. Recent research has also demonstrated the significant involvement of the endocannabinoid system (ECS) in the pathogenesis of several neuropsychiatric diseases, including ASD. In fact, the ECS has the potential to regulate a multitude of metabolic and cellular pathways associated with autism, including the immune system. Moreover, the ECS has emerged as a promising target for intervention with high predictive validity. Particularly noteworthy are resent preclinical studies in rodents, which describe the onset of ASD-like symptoms after various genetic or pharmacological interventions targeting the ECS, providing encouraging evidence for further exploration in this area.

ACE2-Fc and DPP4-Fc decoy receptors against SARS-CoV-2 and MERS-CoV variants: a quick therapeutic option for current and future coronaviruses outbreaks.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the Middle East respiratory syndrome coronavirus (MERS-CoV) are highly pathogenic human coronaviruses (CoVs). Anti-CoVs mAbs and vaccines may be effective, but the emergence of neutralization escape variants is inevitable. Angiotensin-converting enzyme 2 and dipeptidyl peptidase 4 enzyme are the getaway receptors for SARS-CoV-2 and MERS-CoV, respectively. Thus, we reformatted these receptors as Fc-fusion decoy receptors. Then, we tested them in parallel with anti-SARS-CoV (ab1-IgG) and anti-MERS-CoV (M336-IgG) mAbs against several variants using pseudovirus neutralization assay. The generated Fc-based decoy receptors exhibited a strong inhibitory effect against all pseudotyped CoVs. Results showed that although mAbs can be effective antiviral drugs, they might rapidly lose their efficacy against highly mutated viruses. We suggest that receptor traps can be engineered as Fc-fusion proteins for highly mutating viruses with known entry receptors, for a faster and effective therapeutic response even against virus harboring antibodies escape mutations.

Integrated Network Pharmacology Approach to Evaluate Bioactive Phytochemicals of Acalypha indica and Their Mechanistic Actions to Suppress Target Genes of Tuberculosis.

Mycobacterium tuberculosis is responsible for tuberculosis (TB) all over the world. Despite tremendous advancements in biomedical research, new treatment approaches, and preventive measures, TB incidence rates continue to ascend. The herbaceous plant Acalypha indica, also known as Indian Nettle, belongs to the Euphorbiaceae family and is known as one of the most important sources of medicines and pharmaceuticals for the medical therapy for a range of ailments. However, the precise molecular mechanism of its therapeutic action is still unknown. In this study, an integrated network pharmacology approach was employed to explore the potential mechanism of A. indica phytochemicals against TB. The active chemical components of A. indica were collected from two independent databases and published sources, whereas SwissTargetPrediction was used to identify the target genes of these phytochemicals. GeneCards and DisGeNET databases were employed to retrieve tuberculosis-related genes and variants. Following the evaluation of overlapped genes, gene enrichment analysis and PPI network analysis were performed using the DAVID and STRING databases, respectively. Later, to identify the potential target(s) for the disease, molecular docking was performed. A. indica revealed 9 active components with 259 potential therapeutic targets; TB attributed 694 intersecting genes from the two data sets; and both TB and A. indica overlapped 44 potential targets. The in-depth analysis based on the degree revealed that AKT1 and EGFR formed the foundation of the PPI network. Moreover, docking analysis followed by molecular dynamics simulations revealed that phytosterol and stigmasterol have higher binding affinities to AKT1 and EGFR to suppress tuberculosis. This study provides a convincing proof that A. indica can be exploited to target TB after experimental endorsement; further, it lays the framework for more experimental research on A. indica's anti-TB activity.

Extracellular matrix detached cancer cells resist oxidative stress by increasing histone demethylase KDM6 activity.

Epithelial cancer cells rely on the extracellular matrix (ECM) attachment in order to spread to other organs. Detachment from the ECM is necessary for these cells to seed in other locations. When the attachment to the ECM is lost, cellular metabolism undergoes a significant shift from oxidative metabolism to glycolysis. Additionally, the cancer cells become more dependent on glutaminolysis to avoid a specific type of cell death known as anoikis, which is associated with ECM detachment. In our recent study, we observed increased expression of H3K27me3 demethylases, specifically KDM6A/B, in cancer cells that were resistant to anoikis. Since KDM6A/B is known to regulate cellular metabolism, we investigated the effects of suppressing KDM6A/B with GSK-J4 on the metabolic processes in these anoikis-resistant cancer cells. Our results from untargeted metabolomics revealed a profound impact of KDM6A/B inhibition on various metabolic pathways, including glycolysis, methyl histidine, spermine, and glutamate metabolism. Inhibition of KDM6A/B led to elevated reactive oxygen species (ROS) levels and depolarization of mitochondria, while reducing the levels of glutathione, an important antioxidant, by diminishing the intermediates of the glutamate pathway. Glutamate is crucial for maintaining a pool of reduced glutathione. Furthermore, we discovered that KDM6A/B regulates the key glycolytic genes expression like hexokinase, lactate dehydrogenase, and GLUT-1, which are essential for sustaining glycolysis in anoikis-resistant cancer cells. Overall, our findings demonstrated the critical role of KDM6A/B in maintaining glycolysis, glutamate metabolism, and glutathione levels. Inhibition of KDM6A/B disrupts these metabolic processes, leading to increased ROS levels and triggering cell death in anoikis-resistant cancer cells.

Effect of Nk-lysin peptides on bacterial growth, MIC, antimicrobial resistance, and viral activities.

NK-lysins from chicken, bovine and human are used as antiviral and antibacterial agents. Gram-negative and gram-positive microorganisms, including Streptococcus pyogenes, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, Klebsiella oxytoca, Shigella sonnei, Klebsiella pneumoniae and Salmonella typhimurium, are susceptible to NK-lysin treatment. The presence of dominant TEM-1 gene was noted in all untreated and treated bacteria, while TOHO-1 gene was absent in all bacteria. Importantly, ß-lactamase genes CTX-M-1, CTX-M-8, and CTX-M-9 genes were detected in untreated bacterial strains; however, none of these were found in any bacterial strains following treatment with NK-lysin peptides. NK-lysin peptides are also used to test for inhibition of infectivity, which ranged from 50 to 90% depending on NK-lysin species. Chicken, bo vine and human NK-lysin peptides are demonstrated herein to have antibacterial activity and antiviral activity against Rotavirus (strain SA-11). On the basis of the comparison between these peptides, potent antiviral activity of bovine NK-lysin against Rotavirus (strain SA-11) is particularly evident, inhibiting infection by up to 90%. However, growth was also significantly inhibited by chicken and human NK-lysin peptides, restricted by 80 and 50%, respectively. This study provided a novel treatment using NK-lysin peptides to inhibit expression of ß-lactamase genes in ß-lactam antibiotic-resistant bacterial infections.

Prevalence and molecular determinants of carbapenemase-producing Klebsiella pneumoniae isolated from Jazan, Saudi Arabia.

INTRODUCTION: The World Health Organization (WHO) designated Carbapenem-resistant Enterobacterales (CRE), formerly Enterobacteriaceae, among the global priority list of antibiotic-resistant bacteria. The rate of CRE in Arabian countries, including Saudi Arabia has increased. Here, we report the prevalence of carbapenemase-producing Klebsiella pneumoniae (CPKP) in the Jazan region, a southern coastal province of Saudi Arabia. METHODOLOGY: Eighty-six non-repetitive clinical isolates of K. pneumoniae that showed resistance to at least one of the carbapenem drugs were collected from three tertiary hospitals in the Jazan region from March 2020 to April 2021. The identification and antimicrobial susceptibility testing (AST) of isolates were performed using various automated systems. Molecular detection of carbapenemase genes was conducted using a multiplex PCR. RESULTS: Out of the 86 tested CRKP isolates, 64 (74.4%) were carbapenemase-producing isolates. The blaOXA-48 gene was the most predominant carbapenemase gene, detected in 65.1% (n = 56) of isolates. The blaNDM gene was detected in only 9.3% (n = 8) of isolates; three were found to be co-harbored with blaVIM. Interestingly, one isolate of CRKP was found to have carbapenemase genes (blaNDM, blaVIM and blaKPC), which was associated with COVID-19 patient. CONCLUSIONS: The incidence of carbapenemase-producing K. pneumoniae in Jazan hospitals seemed to be high, confirming the continued prevalence of carbapenem resistance in Saudi Hospitals. We report K. pneumoniae strain with triple carbapenemase genes in southern Saudi Arabia. The emergence of such an isolate could threaten patients and healthcare workers and requires great attention to rapid interventions to avoid further dissemination, particularly during the COVID-19 pandemic.

Identification of Gut Microbiota Profile Associated with Colorectal Cancer in Saudi Population.

Colorectal cancer (CRC) is a significant global health concern. Microbial dysbiosis and associated metabolites have been associated with CRC occurrence and progression. This study aims to analyze the gut microbiota composition and the enriched metabolic pathways in patients with late-stage CRC. In this study, a cohort of 25 CRC patients diagnosed at late stage III and IV and 25 healthy participants were enrolled. The fecal bacterial composition was investigated using V3-V4 ribosomal RNA gene sequencing, followed by clustering and linear discriminant analysis (LDA) effect size (LEfSe) analyses. A cluster of ortholog genes' (COG) functional annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to identify enrichment pathways between the two groups. The findings showed that the fecal microbiota between the two groups varied significantly in alpha and beta diversities. CRC patients' fecal samples had significantly enriched populations of Streptococcus salivarius, S. parasanguins, S. anginosus, Lactobacillus mucosae, L. gasseri, Peptostreptococcus, Eubacterium, Aerococcus, Family XIII_AD3001 Group, Erysipelatoclostridium, Escherichia-Shigella, Klebsiella, Enterobacter, Alistipes, Ralstonia, and Pseudomonas (Q < 0.05). The enriched pathways identified in the CRC group were amino acid transport, signaling and metabolism, membrane biogenesis, DNA replication and mismatch repair system, and protease activity (Q < 0.05). These results suggested that the imbalance between intestinal bacteria and the elevated level of the predicated functions and pathways may contribute to the development of advanced CRC tumors. Further research is warranted to elucidate the exact role of the gut microbiome in CRC and its potential implications for use in diagnostic, prevention, and treatment strategies.

Construction of VSVΔ51M oncolytic virus expressing human interleukin-12.

The use of oncolytic viruses (OVs) in combination with cytokines, such as IL-12, is a promising approach for cancer treatment that addresses the limitations of current standard treatments and traditional cancer immunotherapies. IL-12, a proinflammatory cytokine, triggers intracellular signaling pathways that lead to increased apoptosis of tumor cells and enhanced antitumor activity of immune cells via IFN-γ induction, making this cytokine a promising candidate for cancer therapy. Targeted expression of IL-12 within tumors has been shown to play a crucial role in tumor eradication. The recent development of oncolytic viruses enables targeted delivery and expression of IL-12 at the tumor site, thereby addressing the systemic toxicities associated with traditional cancer therapy. In this study, we constructed an oncolytic virus, VSVΔ51M, based on the commercially available VSV wild-type backbone and further modified it to express human IL-12. Our preclinical data confirmed the safety and limited toxicity of the modified virus, VSV-Δ51M-hIL-12, supporting its potential use for clinical development.

Evaluation of the Antibacterial Activity of Quinoxaline Derivative Compound Against Methicillin-Resistant Staphylococcus aureus.

Background: While the frequency of methicillin-resistant Staphylococcus aureus (MRSA) continues to rise globally, there is a fear regarding an increase in vancomycin resistance among S. aureus strains. As far back as the 1960s, MRSA was one of the world's most prevalent antibiotic-resistant bacteria. Among hospitalized patients and community members, MRSA is the cause of a significant number of infections. As a result of its resistance to classical beta-lactam and, in some cases, vancomycin antibiotics, efforts must be made as soon as feasible to find a new approach to fighting MRSA. Purpose: This study is designed to evaluate the antibacterial activity of quinoxaline derivative compound against MRSA in comparison with vancomycin as a reference drug. Methods: Sixty MRSA isolates were subjected to susceptibility testing by broth microdilution method for quinoxaline derivative compound and vancomycin. Each drug's minimal inhibitory concentration (MIC) was determined and compared. Results: Among the sixty MRSA isolates, most of the quinoxaline derivative compound MIC findings (56.7%) were 4 µg/mL compared to vancomycin MIC values (63.3%) of 4 µg/mL. In comparison, 20% of quinoxaline derivative compound MIC readings were 2 µg/mL, while the vancomycin MIC results were 6.7%. However, the overall proportion of MIC readings at ≤2 µg/mL for both antibacterial agents was equal (23.3%). None of the isolates were resistant to vancomycin. Conclusion: This experiment revealed that most MRSA isolates were associated with low MICs (1-4 µg/mL) for quinoxaline derivative compound. Overall, the susceptibility of the quinoxaline derivative compound signifies a promising efficacy against MRSA and may set a novel treatment approach.

A Novel Homozygous Nonsense Variant in the DYM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family.

(1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the DYM gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In the present study, large consanguineous families with five affected individuals with osteochondrodysplasia phenotypes were recruited. The family members were analyzed by polymerase chain reaction for homozygosity mapping using highly polymorphic microsatellite markers. Subsequent to linkage analysis, the coding exons and exon intron border of the DYM gene were amplified. The amplified products were then sent for Sanger sequencing. The structural effect of the pathogenic variant was analyzed by different bioinformatics tools. (3) Results: Homozygosity mapping revealed a 9 Mb homozygous region on chromosome 18q21.1 harboring DYM shared by all available affected individuals. Sanger sequencing of the coding exons and exon intron borders of the DYM gene revealed a novel homozygous nonsense variant [DYM (NM_017653.6):c.1205T>A, p.(Leu402Ter)] in affected individuals. All the available unaffected individuals were either heterozygous or wild type for the identified variant. The identified mutation results in loss of protein stability and weekend interactions with other proteins making them pathogenic (4) Conclusions: This is the second nonsense mutation reported in a Pakistani population causing DMC. The study presented would be helpful in prenatal screening, genetic counseling, and carrier testing of other members in the Pakistani community.

Mouth rinses efficacy on salivary SARS-CoV-2 viral load: A randomized clinical trial.

Considering the global trend to confine the COVID-19 pandemic by applying various preventive health measures, preprocedural mouth rinsing has been proposed to mitigate the transmission risk of SARS-CoV-2 in dental clinics. The study aimed to investigate the effect of different mouth rinses on salivary viral load in COVID-19 patients. This study was a single-center, randomized, double-blind, six-parallel-group, placebo-controlled clinical trial that investigated the effect of four mouth rinses (1% povidone-iodine, 1.5% hydrogen peroxide, 0.075% cetylpyridinium chloride, and 80 ppm hypochlorous acid) on salivary SARS-CoV-2 viral load relative to the distilled water and no-rinse control groups. The viral load was measured by quantitative reverse transcription PCR (RT-qPCR) at baseline and 5, 30, and 60 min post rinsing. The viral load pattern within each mouth rinse group showed a reduction overtime; however, this reduction was only statistically significant in the hydrogen peroxide group. Further, a significant reduction in the viral load was observed between povidone-iodine, hydrogen peroxide, and cetylpyridinium chloride compared to the no-rinse group at 60 min, indicating their late antiviral potential. Interestingly, a similar statistically significant reduction was also observed in the distilled water control group compared to the no-rinse group at 60 min, proposing mechanical washing of the viral particles through the rinsing procedure. Therefore, results suggest using preprocedural mouth rinses, particularly hydrogen peroxide, as a risk-mitigation step before dental procedures, along with strict adherence to other infection control measures.

Chicken ß-defensin-1 peptide as a candidate anticoccidial agent in broiler chickens.

The current study aimed to investigate the potentiality of using avian ß-defensin-1 peptide as a candidate agent against coccidiosis infection in broiler chicken.We employed an in-silico analysis to study the primary structure of ß-defensin-1 peptide as well as its 3-D and molecular dynamic structures. This will also enable obtaining adequate information about the mode of action of these peptides and the intra-cellular transduction pathways. The results revealed no significant difference among groups of broiler chicken in terms of body weight before the Eimeria challenge.The results of our study indicated a significant reduction in oocyst count in birds administered ß-defensin-1 peptide treatment, vis-a-vis healthy birds. The treated group showed a 2-3 times reduction in oocyst count, compared to the positive control group. The Eimeria oocysts count evaluated for birds administered with ß-defensin-1 after the Eimeria challenge showed a significant difference. The study indicated significant reduction and down-regulation in the level of expression of ß-defensin 1 and 4 in the control and treatment groups.This electrostatic profile and hydrophobicity regulate the functioning of this peptide. The results may help in the development of novel approaches that could be used as alternatives or adjunct to the existing means of coccidiosis control in broilers.

Green Synthesis of Zn(OH)2/ZnO-Based Bionanocomposite using Pomegranate Peels and Its Application in the Degradation of Bacterial Biofilm.

The ability and potency of bacterial species to form biofilms, which show antibiotic resistance thereby avoiding antibiotic surfaces, is a major cause of prolonged infections. Various advanced approaches have been employed to prevent or damage bacterial biofilms, formed by a variety of bacterial strains, to help prevent the associated infectious disease. In this context, zinc-based nanostructures have been recognized as a potential antibiotic agent against a broad spectrum of bacterial communities. As a result, a sustainable and green synthesis method was adapted in the present study to synthesize a Zn(OH)2/ZnO-based bionanocomposite, in which aqueous extracts of waste pomegranate peels (Punica granatum) were employed as a natural bioreducing agent to prepare the bionanocomposite at room temperature. Furthermore, FT-IR, XRD, DLS, UV-Visible, PL spectroscopy, FE-SEM, and TEM were used to characterize the green route synthesized a Zn(OH)2/ZnO bionanocomposite. The average crystallite size was determined using the Scherrer relation to be 38 nm, and the DLS results indicated that the Zn(OH)2/ZnO bionanocomposite had a hydrodynamic size of 170 nm. On the other hand, optical properties investigated through UV-Vis and PL spectroscopy explored the energy bandgap between 2.80 and 4.46 eV, corresponding to the three absorption edges, and it covered the blue spectrum when the sample was excited at 370 nm. Furthermore, the impact of this green route synthesized a Zn(OH)2/ZnO bionanocomposite on the biofilm degradation efficiency of the pathogenic bacterial strain Bacillus subtilis PF_1 using the Congored method was investigated. The Congored assay clearly explored the biofilm degradation efficiency in the presence of a 50 mg/mL and 75 mg/mL concentration of the Zn(OH)2/ZnO bionanocomposite against the bacterial strain Bacillus subtilis PF_1 grown for 24 h. This study can be further applied to the preparation of bionanocomposites following a low-cost green synthesis approach, and thus prepared nanostructures can be exploited as advanced antimicrobial agents, which could be of great interest to prevent various infectious diseases.

In Vitro and In Vivo Anti-Arthritic Potential of Caralluma tuberculata N. E. Brown. and Its Chemical Characterization.

Present research was planned to assess the in vitro and in vivo anti-arthritic potential of Caralluma tuberculata N. E. Brown. methanolic (CTME) and aqueous (CTAQ) extracts. Chemical characterization was done by high-performance liquid chromatography and gas chromatography−mass spectrometry analysis. The Complete Freund's Adjuvant (CFA) was injected in left hind paw of rat at day 1 and dosing at 150, 300 and 600 mg/kg was started on the 8th day via oral gavage in all groups except normal and disease control rats (which were given distilled water), whereas methotrexate (intraperitoneal; 1 mg/kg/mL) was administered to standard control. The CTME and CTAQ exerted significant (p < 0.01−0.0001) in vitro anti-arthritic action. Both extracts notably reduced paw edema, and restored weight loss, immune organs weight, arthritic score, RBCs, ESR, platelet count, rheumatoid factor (RF), C-reactive protein, and WBCs in treated rats. The plant extracts showed significant (p < 0.05−0.0001) downregulation of tumor necrosis factor-α, Interleukin-6, -1ß, NF-κB, and cyclooxygenase-2, while notably upregulated IL-4, IL-10, I-κBα in contrast to disease control rats. The plant extracts noticeably (p < 0.001−0.0001) restored the superoxide dismutase and catalase activities and MDA levels in treated rats. Both extracts exhibited significant anti-arthritic potential. The promising potential was exhibited by both extracts probably due to phenolic, and flavonoids compounds.

Recent Update on anaerobic digestion of paddy straw for biogas production: Advancement, limitation and recommendations.

At present, development and production of advanced green energy sources are highly demanded, and this may offer a clean and sustainable environment to our modern society. In this reference, biogas is emerging as a promising green energy source and seems to have high potential to replace fossil-fuel based energy sources in the coming future. Further, lignocellulosic biomass (LCB) based biogas production technology has been found to be highly promising owing to several advantages associated therewith. Rich inorganic content, renewable nature, huge availability and low-cost are the key beneficial factors of LCB-based feedstock l to produce biogas. Among the varieties of LCB, paddy straw is one of the most demanding feedstocks and is highly rich in organic compounds that are imperative to producing biogas. Nevertheless, it is noticed that paddy straw as a waste material is usually disposed-off by direct burning, whereas it exhibits low natural digestibility due to the presence of high lignin and silica content which causes severe environmental pollution. On the other hand, paddy straw can be a potential feedstock to produce biogas through anaerobic digestion. Therefore, based on the current ongoing research studies worldwide, this review evaluates the advancements made in the AD process. Meanwhile, existing limitations and future recommendations to improve the yield and productivity of the biogas using paddy straw have been discussed. The emphasis has also been given to various operational parameters developments, related shortcomings, and strategies to improve biogas production at pilot scale.

Bacterial co-infections and antimicrobial resistance associated with the Coronavirus Disease 2019 infection.

Bacterial co-infections are typically associated with viral respiratory tract infections and pose a significant public health problem around the world. COVID-19 infection damages tissues lining the respiratory track and regulates immune cells/cytokines leading to microbiome dysbiosis and facilitating the area to be colonized by pathogenic bacterial agents. There have been reports of different types of bacterial co-infection in COVID-19 patients. Some of these reports showed despite geographical differences and differences in hospital settings, bacterial co-infections are a major cause of morbidity and mortality in COVID-19 patients. The inappropriate use of antibiotics for bacterial infections, particularly broad-spectrum antibiotics, can also further complicate the infection process, often leading to multi drug resistance, clinical deterioration, poor prognosis, and eventually death. To this end, researchers must establish a new therapeutic approach to control SARS-CoV-2 and the associated microbial coinfections. Hence, the aim of this review is to highlight the bacterial co-infection that has been recorded in COVID-19 patients and the status of antimicrobial resistance associated with the dual infections.

Apigenin Loaded Lipoid-PLGA-TPGS Nanoparticles for Colon Cancer Therapy: Characterization, Sustained Release, Cytotoxicity, and Apoptosis Pathways.

Colon cancer (CC) is one of major causes of mortality and affects the socio-economic status world-wide. Therefore, developing a novel and efficient delivery system is needed for CC management. Thus, in the present study, lipid polymer hybrid nanoparticles of apigenin (LPHyNPs) was prepared and characterized on various parameters such as particle size (234.80 ± 12.28 nm), PDI (0.11 ± 0.04), zeta potential (−5.15 ± 0.70 mV), EE (55.18 ± 3.61%), etc. Additionally, the DSC, XRD, and FT-IR analysis determined drug entrapment and affinity with the selected excipient, demonstrating a promising drug affinity with the lipid polymer. Morphological analysis via SEM and TEM exhibited spherical NPs with a dark color core, which indicated drug entrapment inside the core. In vitro release study showed significant (p < 0.05) sustained release of AGN from LPHyNPs than AGN suspension. Further, the therapeutic efficacy in terms of apoptosis and cell cycle arrest of developed LPHyNPs against CC was estimated by performing flow cytometry and comparing its effectiveness with blank LPHyNPs and AGN suspension, which exhibited remarkable outcomes in favor of LPHyNPs. Moreover, the mechanism behind the anticancer attribute was further explored by estimating gene expression of various signaling molecules such as Bcl-2, BAX, NF-κB, and mTOR that were involved in carcinogenic pathways, which indicated significant (p < 0.05) results for LPHyNPs. Moreover, to strengthen the anticancer potential of LPHyNPs against chemoresistance, the expression of JNK and MDR-1 genes was estimated. Outcomes showed that their expression level reduced appreciably when compared to blank LPHyNPs and AGN suspension. Hence, it can be concluded that developed LPHyNPs could be an efficient therapeutic system for managing CC.

Improved biohydrogen production via graphene oxide supported granular system based on algal hydrolyzate, secondary sewage sludge and bacterial consortia.

Biohydrogen production using renewable sources has been regarded as one of the most sustainable ways to develop low-cost and green production technology. In order to achieve this objective, herein biohydrogen production has been conducted using the combination of untreated secondary sewage sludge (Sss), algal biomass hydrolyzate (Abh), graphene oxide (GO) and bacterial consortia that forms a granular system. Thus, naturally formed granular system produced cumulative H2 of 1520 mL/L in 168 h with the maximum production rate of 13.4 mL/L/h in 96 h at initial pH 7.0, and optimum temperature of 37 °C. It is noticed that the combination of Abh, Sss and GO governed medium showed 42.05 % higher cumulative H2 production along with 22.71 % higher production rate as compared to Abh and Sss based H2 production medium. The strategy presented herein may find potential applications for the low-cost biohydrogen production using waste biomasses including Sss and Abh.

Anticancer activity of chicken cathelicidin peptides against different types of cancer.

BACKGROUND: This study served as the pioneer in studying the anti-cancer role of chicken cathelicidin peptides. METHODS AND RESULTS: Chicken cathelicidins were used as anticancer agent against the breast cancer cell line (MCF-7) and human colon cancer cell line (HCT116). In addition, the mechanism of action of the interaction of cationic peptides with breast cancer cell line MCF-7 was also investigated. An in vivo investigation was also achieved to evaluate the role of chicken cathelicidin in Ehrlich ascites cell (EAC) suppression as a tumor model after subcutaneous implantation in mice. It was found during the study that exposure of cell lines to 40 µg/ml of chicken cathelicidin for 72 h reduced cell lines growth rate by 90-95%. These peptides demonstrated down-regulation of (cyclin A1 and cyclin D genes) of MCF-7 cells. The study showed that two- and three-fold expression of both of caspase-3 and - 7 genes in untreated MCF-7 cells compared to treated MCF-7 cells with chicken cathelicidin peptides. Our data showed that chicken (CATH-1) enhance releasing of TNFα, INF-γ and upregulation of granzyme K in treated mice groups, in parallel, the tumor size and volume was reduced in the treated EAC-bearing groups. Tumor of mice groups treated with chicken cathelicidin displayed high area of necrosis compared to untreated EAC-bearing mice. Based on histological analysis and immunohistochemical staining revealed that the tumor section in Ehrlich solid tumor exhibited a strong Bcl2 expression in untreated control compared to mice treated with 10 & 20 µg of cathelicidin. Interestingly, low expression of Bcl2 were observed in mice taken 40 µg/mL of CATH-1. CONCLUSIONS: This study drive intention in treatment of cancer through the efficacy of anticancer efficacy of chicken cathelicidin peptides.