Unlocking the potential of phenyl boronic acid functionalized-quercetin nanoparticles: Advancing antibacterial efficacy and diabetic wound healing.

This study investigates the novel application of Phenyl Boronic Acid Functionalized-Quercetin nanoparticles (PBA-Qt NPs) in the context of antibacterial and diabetic wound healing. The research reveals a multifaceted approach, encompassing physicochemical characterization, antioxidant activity, antibacterial potential, and wound healing efficacy. The purpose of the study was to improve wound healing and antibacterial effects of quercetin and its esterified nanoparticles with phenyl boronic acid (PBA-Qt) compared with phenytoin streptozotocin-induced diabetic rats as a model. PBA-Qt NPs were confirmed using TLC, SEM, and FTIR. They exhibited superior DPPH scavenging (84.2 ± 0.12 %) compared to PBA (59.00 ± 0.18 %) and quercetin (79.02 ± 0.17 %). PBA-Qt showed significant antimicrobial properties with ZOI against Gram-negative (30.34 ± 0.02) and Gram-positive bacteria (25.40 ± 0.03). The MIC for Pseudomonas aeruginosa was 1.41 ± 0.03 µg/100 µL, and for Staphylococcus aureus, it was 8.25 ± 0.02 µg/100 µL. The MBC against Pseudomonas aeruginosa was 4.33 ± 0.02 µg/100 µL, and for Staphylococcus aureus, it was 8.25 ± 0.02 µg/100 µL. PBA-Qt NPs reduced MIC for both Gram-positive and Gram-negative bacteria compared to quercetin. They enhanced wound healing by 60-99 % in infected diabetic rats, outperforming phenytoin. PBA-Qt NPs stimulated angiogenesis, tissue repair, and regeneration, improving wound closure. In diabetic and non-diabetic wounds, PBA-Qt NPs demonstrated superior wound contraction and granulation tissue formation. In conclusion, PBA-Qt nanoparticles are promising for treating diabetic chronic wounds due to reduced irritation and enhanced antibacterial and wound-healing properties.

Survival, growth, behavior, hematology and serum biochemistry of mice under different concentrations of orally administered amorphous silica nanoparticle.

Silica nanoparticles (SiNPs) are used extensively in consumer products and biomedical research basically due to ease of production and low cost. However, insufficient literature is reported regarding the toxicity and biocompatibility of SiNPs. The present study aimed to investigate the potential role of amorphous SiNPs on survival, growth, behavioral alterations, hematology and serum biochemistry of mice at four concentrations (control, 50, 100 and 150 mg/kg/day) of an oral supplementation for a period of 3 months. Signs of toxicity (lethargy, nausea, coma, tremors, vomiting and diarrhea, etc.) were noted at 9:00 am and 9:00 pm (twice a day) and the body weight of each of these mice was measured every week. The data were subjected to mean, standard deviation (S.D). Moreover, One-Way Analysis of Variance (ANOVA) and Dunnett's test were applied for analysis of statistical significance between groups by using SPSS software, version 20. All the mice survived with minor alterations in behavior and no significant weight changes were observed during the stipulated time period. Complete blood count (CBC) analysis indicated non-significant (P ≥ 0.05) systemic dysfunctions of organ systems. However, there was elevation in the level of AST and ALT in the analysis of serum biochemistry, while the values of all other examined parameters were not-significant (P ≥ 0.05). The study concluded that orally administered large silica nanoparticles up to the dose level of 150 mg/kg/day are nontoxic for the in vivo use in mice.

Growth Response in Oryctolagus cuniculus to Selenium Toxicity Exposure Ameliorated with Vitamin E.

The adverse impacts of high temperature during the summer season on the rabbit industry have gained increased global attention. In this study, the comparative effects of biological (BIO) and chemical (CH) nanoselenium (nano-Se) combined with vitamin E on the growth and immune performances of rabbits were observed. A total of 200 white male rabbits of similar age (90 days) were divided into five treatment groups (T0, T1, T2, T3, and T4), 40 animals in each treatment. The rabbits in the first treatment group (T0) was fed basal diet; (T1) basal diet supplemented with 35 mg biological synthesized nanoselenium/kg diet; (T2) basal diet with 35 mg biological nanoselenium/kg diet+150 mg Vit. E/kg; (T3) basal diet+35 m chemically synthesized nanoselenium/kg diet; and (T4) basal diet+35 mg of chemical nanoselenium/kg diet+150 mg Vit. E/kg. The duration of this experiment was 63 days. The body weight of each rabbit was recorded weekly. Results revealed a significant (P < 0.05) increase in live body weight (LBW), total body gain (TBG), and feed conversion ratio (FCR) of rabbits treated with BIO-Se+Vit. E (T2) compared to the other groups. Selenium concentrations in the kidneys and liver were significantly higher (P < 0.05) in animals fed with BIO-Se+Vit. E (T2). The concentrations of serum urea, glutamyl transferase (GGT), and triglycerides (TG) were lower in untreated (T0) and treated groups (T1, T2, T3, and T4). From the results of this study, it can be concluded that biological nano-Se gave maximum improvement for the parameters under study compared to the chemically synthesized nanoselenium by playing a role in alleviating heat stress, increasing the growth performance, and enhancing the immunity of growing white male rabbits. Further addition of Vit. E is an alternative method to maximize productivity with no adverse effects during the fattening period of growing white male rabbits.

Integrative analysis reveals methylenetetrahydrofolate dehydrogenase 1-like as an independent shared diagnostic and prognostic biomarker in five different human cancers.

BACKGROUND: Defects in methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) expression have earlier been examined in only a few human cancers. OBJECTIVES: Multi-omics profiling of MTHFD1L as a shared biomarker in distinct subtypes of human cancers. METHODS: In the current study, for the multi-omics analysis of MTHFD1L in 24 major subtypes of human cancers, a comprehensive in silico approach was adopted to mine different open access online databases including UALCAN, Kaplan-Meier (KM) plotter, LOGpc, GEPIA, Human Protein Atlas (HPA), Gene Expression across Normal and Tumor tissue (GENT2), MEXPRESS, cBioportal, STRING, DAVID, TIMER, and Comparative Toxicogenomics Database (CTD). RESULTS: We noticed that the expression of MTHFD1L was significantly higher in all the analyzed 24 subtypes of human cancers as compared with the normal controls. Moreover, MTHDF1L overexpression was also found to be significantly associated with the reduced overall survival (OS) duration of Bladder urothelial cancer (BLCA), Head and neck cancer (HNSC), Kidney renal papillary cell carcinoma (KIRP), Lung adenocarcinoma (LUAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that MTHFD1L plays a significant role in the development and progression of these cancers. We further noticed that MTHFD1L was also overexpressed in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of MTHFD1L-associated genes in five diverse pathways. We also explored few interesting correlations between MTHFD1L expression and its promoter methylation, genetic alterations, CNVs, and between CD8+ T immune cells level. CONCLUSION: In conclusion, our results elucidated that MTHFD1L can serve as a shared diagnostic and prognostic biomarker in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features.

Multi-Omics Analysis Identified TMED2 as a Shared Potential Biomarker in Six Subtypes of Human Cancer.

INTRODUCTION: Cancer is one of the most common malignancies and the leading cause of death worldwide. As a member of the transmembrane emp24 domain (Tmed)/p24 family of proteins, TMED2 expression variations have been documented earlier in only a few subtypes of human cancers, and the multi-omics profiling of TMED2 as a shared biomarker in different other subtypes of human cancers remains to be uncovered. METHODS: In the current study, TMED2 multi-omics analysis in 24 major subtypes of human cancer was performed using different authentic online databases and bioinformatics analysis including UALCAN, Kaplan-Meier (KM) plotter, Human Protein Atlas (HPA), GENT2, MEXPRESS, cBioportal, STRING, DAVID, TIMER, and CTD. RESULTS: In general, the TMED2 expression in 24 major subtypes of human cancers was higher relative to normal controls and was also strongly associated with the lower overall survival (OS) and relapse-free survival (RFS) duration of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. This implies that TMED2 plays a significant role in the development and progression of these cancers. Furthermore, the TMED2 overexpression was also correlated with different clinicopathological features of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. TMED2-associated genes network was involved in 3 diverse pathways, and finally, few stronger correlations were also explored between TMED2 expression and its promoter methylation level, genetic alterations, and CD8+ T immune cells level. CONCLUSION: In conclusion, via this in silico study, we have elucidated that TMED2 can serve as a shared diagnostic and prognostic biomarker in CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients of different clinicopathological features but, further in vitro and in vivo research should be carried out to confirm these findings.

CTHRC1 expression is a novel shared diagnostic and prognostic biomarker of survival in six different human cancer subtypes.

According to the previous reports, the collagen triple helix repeat containing 1 (CTHRC1) causes tumorigenesis by modulating the tumor microenvironment, however, the evidence is limited to a few human cancer subtypes. In the current study, we analyzed and validated the CTHRC1 expression variations in 24 different human cancer tissues paired with normal tissues using publically available databases. We observed that CTHRC1 was overexpressed in all the 24 major subtypes of human cancers and its overexpression was significantly associated with the reduced overall survival (OS) duration of head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), Lung adenocarcinoma (LUAD), stomach adenocarcinoma (STAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that CTHRC1 plays a significant role in the development and progression of these cancers. We further noticed that CTHRC1 was also overexpressed in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of CTHRC1 associated genes in seven diverse pathways. We also explored few interesting correlations between CTHRC1 expression and promoter methylation, genetic alterations, CNVs, CD8+ T immune cells infiltration, and tumor purity. In conclusion, CTHRC1 can serve as a shared diagnostic and prognostic biomarker in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features.

Evaluation of DNA vaccines encoding M. Tb gene Bfrb and Mpt32 in mice model.

Tuberculosis (TB) is a life threatening infectious disease which is prevalent throughout the world. Mycobacterium bovis based Bacille Calmette-Gue´rin (BCG) is the only vaccine available against TB however, this (single) vaccine is not enough to eradicate it. Furthermore, numbers of researches from different parts of the World have shown its efficacy as variable. Hence other (better) vaccines like DNA vaccines are needed in addition to BCG in order to achieve desired goal of TB eradication. The current study was aimed to develop subunit based DNA vaccines against TB and to check their efficacy. Two constructs Bfrb-pND14 and Mpt32-pND14 were made and used as DNA vaccines. Endotoxin free DNA preparations were made and used in immunization studies. Twenty Balb/c female mice of age eight weeks were used in trial. Two experimental groups each comprising eight animals were used to inoculate Mpt32-pND14 and Bfrb-pND14 vaccines respectively. A group of four animals was used as negative control. Animals were bled through tail periodically and finally through cardiac puncture before euthanization. Antibodies were confirmed through dot blot and Agar Gel Immuno Diffusion test (AGID). All the animals immunized with both vaccines were found positive as tested through dot blot and AGID. The results of this study have indicated that both the M. tb genes have produced strong immune response in mice model through pND14 vector and proved themselves as good subunit based DNA vaccines.