Exploring the mechanistic role of silk sericin biological and chemical conjugates for effective acute and chronic wound repair and related complications.

OBJECTIVE: The current review is designed to elaborate and reveal the underlying mechanism of sericin and its conjugates of drug delivery during wounds and wound-related issues. SIGNIFICANCE: Wound healing is a combination of different humoral, molecular, and cellular mechanisms. Various natural products exhibit potential in wound healing but among them, sericin, a domestic silkworm catches much attention of researchers due to its bio-functional properties such as biodegradable, biocompatible, anti-oxidant, anti-bacterial, photo-protector, anti-inflammatory and moisturizing agent. METHODS AND RESULTS: Sericin triggers the activity of anti-inflammatory cytokines which decrease cell adhesion and promote epithelial cell formation. Moreover, sericin enhances the anti-oxidant enzymes in the wounded area which scavenge the toxic consequences of reactive species (ROS). CONCLUSIONS: This article highlights the mechanisms of how topical administration of sericin formulations along with 4-hexylresorcinol,\Chitosan\Ag@MOF-GO, polyvinyl alcohol (PVA), platelet lysate and UV photo cross-linked hydrogel sericin methacrylate which recruits a large number of cytokines on wounded area that stimulate fibroblasts and keratinocyte production as well as collagen deposition that led to early wound contraction. It also reviews the different sericin-based nanoparticles that play a significant role in rapid wound healing.

Synthesis, Characterization, Phytochemistry, and Therapeutic Potential of Azadirachta indica Conjugated Silver Nanoparticles: A Comprehensive Study on Antidiabetic and Antioxidant Properties.

Nanotechnology has become a major topic of study, particularly in the medical and health domains. Because nanomedicine has a higher recovery rate than other conventional drugs, it has attracted more attention. Green synthesis is the most efficient and sustainable method of creating nanoparticles. The current work used ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray, and X-ray diffraction to thoroughly characterize the synthesized silver nanoparticles (AgNPs) from Azadirachta indica leaf extract. Characterization confirmed the synthesis of the AgNPs along with the possible linkage of the phytochemicals with the silver as well as the quantitative analysis and nature of NPs. The antioxidant activity of AgNPs and neem extract was measured by the 2,2-diphenyl-1-picrylhydrazyl assay using various concentrations (20, 40, 60, 80, and 100 µg/ml). Additionally, using diabetic mice that had been given alloxan, the in vivo antidiabetic potential of biosynthesized AgNPs was assessed. Eight groups of mice were used to assess the antidiabetic activity: one control group and seven experimental groups (untreated, extract-treated, AgNPs at low and high doses, standard drug, low dose of AgNPs + drug, and high dose of AgNPs + drug). At days 0, 7, 14, 21, and 28, blood glucose levels and body weight were measured. After 28 days, the mice were dissected, and the liver, kidney, and pancreas were examined histologically. The results depicted that the AgNPs showed higher (significant) radical scavenging activity (IC50 = 35.2 µg/ml) than extract (IC50 = 93.0 µg/ml) and ascorbic acid (IC50 = 64.6 µg/ml). The outcomes demonstrated that biosynthesized AgNPs had a great deal of promise as an antidiabetic agent and exhibited remarkable effects in diabetic mice given AgNPs, extract, and drug. Remarkable improvement in the body weight and blood glucose level of mice treated with high doses of AgNPs and drug was observed. The body weight and blood glucose level of diabetic mice treated with a high dose of AgNPs + standard drug showed significant improvement, going from 28.7 ± 0.2 to 35.6 ± 0.3 g and 248 ± 0.3 to 109 ± 0.1 mg/dl, respectively. Significant regeneration was also observed in the histomorphology of the kidney, liver's central vein, and islets of Langerhans after treatment with biosynthesized AgNPs. Diabetic mice given a high dose of AgNPs and drug displayed architecture of the kidney, liver, and pancreas that was nearly identical to that of the control group. According to the current research, biosynthesized AgNPs have strong antioxidant and antidiabetic potential and may eventually provide a less expensive option for the treatment of diabetes.

Inflammatory response of nanoparticles: Mechanisms, consequences, and strategies for mitigation.

Numerous nano-dimensioned materials have been generated as a result of several advancements in nanoscale science such as metallic nanoparticles (mNPs) which have aided in the advancement of related research. As a result, several significant nanoscale materials are being produced commercially. It is expected that in the future, products that are nanoscale, like mNPs, will be useful in daily life. Despite certain benefits, widespread use of metallic nanoparticles and nanotechnology has negative effects and puts human health at risk because of their continual accumulation in closed biological systems, along with their complex and diverse migratory and transformation pathways. Once within the human body, nanoparticles (NPs) disrupt the body's natural biological processes and trigger inflammatory responses. These NPs can also affect the immune system by activating separate pathways that either function independently or interact with one another. Cytotoxic effects, inflammatory response, genetic material damage, and mitochondrial dysfunction are among the consequences of mNPs. Oxidative stress and reactive oxygen species (ROS) generation caused by mNPs depend upon a multitude of factors that allow NPs to get inside cells and interact with biological macromolecules and cell organelles. This review focuses on how mNPs cause inflammation and oxidative stress, as well as disrupt cellular signaling pathways that support these effects. In addition, possibilities and problems to be reduced are addressed to improve future research on the creation of safer and more environmentally friendly metal-based nanoparticles for commercial acceptance and sustainable use in medicine and drug delivery.

Methanolic extracts of litchi (Litchi chinensis Sonn.): A novel approach of targeting glucose-6-phosphate dehydrogenase for liver cancer therapy.

Cancer metabolism has emerged as a potential target for innovative therapeutic approaches in the treatment of cancer. Cancer metabolism has received much attention, particularly in relation to glucose metabolism. It has been observed that human malignancies have high levels of glucose-6-phosphate dehydrogenase (G6PD) activity which is an important enzyme of glucose metabolism. This overactivity is associated with the cell death and angiogenesis, highlighting its potential as a viable target for cancer treatment. This study was conducted to examine the methanolic extracts from the seeds, bark and leaves of litchi (Litchi chinensis Sonn.) in order to discover effective compounds targeting G6PD and potentially active entities against liver cancer. Plant extract screening for the target protein was carried out through enzymatic activity assay. The recombinant plasmid pET-24a-HmG6PD was expressed in E. coli (BL21-DE3) strain, then purified and assessed using metal affinity chromatography with Ni-NTA columns and SDS-PAGE. The cytotoxicity of plant extracts against liver cancer HepG2 cells was assessed using the MTT assay. All three extracts demonstrated significant inhibitory effects (>80% inhibition) against G6PD. They were then subjected to testing at various concentrations, and their IC50 values were subsequently determined. The extracts of litchi (leaf, IC50: 1.199 µg/mL; bark, IC50: 2.350 µg/mL; seeds, IC50: 1.238 µg/mL) displayed significant inhibition of G6PD activity at lower concentrations. Subsequently, the leaf extract of litchi was further assessed for its impact on HepG2 cell lines in a dose-dependent manner and exhibited strong potential as an inhibitor of cancer cell progression. Moreover, the results of acute toxicity study in mice revealed nontoxic effects of litchi leaf extract on hepatocytes. The results imply that Litchi chinensis leaf extract could be considered as a promising candidate for safer drug development in the treatment of liver cancer.

Integrating genomics, phenomics, and deep learning improves the predictive ability for Fusarium head blight-related traits in winter wheat.

Fusarium head blight (FHB) remains one of the most destructive diseases of wheat (Triticum aestivum L.), causing considerable losses in yield and end-use quality. Phenotyping of FHB resistance traits, Fusarium-damaged kernels (FDK), and deoxynivalenol (DON), is either prone to human biases or resource expensive, hindering the progress in breeding for FHB-resistant cultivars. Though genomic selection (GS) can be an effective way to select these traits, inaccurate phenotyping remains a hurdle in exploiting this approach. Here, we used an artificial intelligence (AI)-based precise FDK estimation that exhibits high heritability and correlation with DON. Further, GS using AI-based FDK (FDK_QVIS/FDK_QNIR) showed a two-fold increase in predictive ability (PA) compared to GS for traditionally estimated FDK (FDK_V). Next, the AI-based FDK was evaluated along with other traits in multi-trait (MT) GS models to predict DON. The inclusion of FDK_QNIR and FDK_QVIS with days to heading as covariates improved the PA for DON by 58% over the baseline single-trait GS model. We next used hyperspectral imaging of FHB-infected wheat kernels as a novel avenue to improve the MT GS for DON. The PA for DON using selected wavebands derived from hyperspectral imaging in MT GS models surpassed the single-trait GS model by around 40%. Finally, we evaluated phenomic prediction for DON by integrating hyperspectral imaging with deep learning to directly predict DON in FHB-infected wheat kernels and observed an accuracy (R2 = 0.45) comparable to best-performing MT GS models. This study demonstrates the potential application of AI and vision-based platforms to improve PA for FHB-related traits using genomic and phenomic selection.

Influence of agro-wastes derived biochar and their composite on reducing the mobility of toxic heavy metals and their bioavailability in industrial contaminated soils.

The agro-waste derived valuable products are prime interest for effective management of toxic heavy metals (THMs). The present study investigated the efficacy of biochars (BCs) on immobilization of THMs (Cr, Zn, Pb, Cu, Ni and Cd), bioaccumulation and health risk. Agro-wastes derived BCs including wheat straw biochar (WSB), orange peel biochar (OPB), rice husk biochar (RHB) and their composite biochar (CB) were applied in industrial contaminated soil (ICS) at 1% and 3% amendments rates. All the BCs significantly decreased the bioavailable THMs and significantly (p < 0.001) reduced bioaccumulation at 3% application with highest efficiency for CB followed by OPB, WSB and RHB as compared to control treatment. The bioaccumulation factor (BAF), concentration index (CI) and ecological risk were decreased with all BCs. The hazard quotient (HQ) and hazard index (HI) of all THMs were <1, except Cd, while carcer risk (CR) and total cancer risk index (TCRI) were decreased through all BCs. The overall results depicted that CB at 3% application rate showed higher efficacy to reduce significantly (p < 0.001) the THMs uptake and reduced health risk. Hence, the present study suggests that the composite of BCs prepared from agro-wastes is eco-friendly amendment to reduce THMs in ICS and minimize its subsequent uptake in vegetables.

The present study has a scientific research scope, based on reduction of bioavailability and bioaccumulation of toxic heavy metals (THMs) by the addition of biochars derived from agro-wastes and their composite biochar (CB), thereby decreasing the potential health risk. Limited study has been conducted, especially on the impact of CB in THMs-contaminated soil. This study could fill the scientific research gap and provides useful information for mitigation of THMs present in contaminated soil, which could be followed by the Environmental Protection Agency, Ministry of Agriculture and farmers in degraded lands.

Comparative transcriptome analysis reveals disruption of Plutella xylostella immune system by fungal peptide cyclosporin C.

The diamondback moth (Plutella xylostella), a major threat to crucifers across the globe, has developed resistance against the majority of insecticides enhancing the need for alternate control measures against this pest. Recently cyclosporin C, a secondary metabolite produced by the insect pathogenic fungus Purpeocillium lilacinum, has been reported to induce lethal and sub-lethal effects against P. xylostella. To date, little is known about the molecular mechanisms of interaction between cyclosporin C and P. xylostella immune systems. This study reports the transcriptome-based immune response of P. xylostella to cyclosprin C treatment. Our results showed differential expression of 322, 97, and 504 differentially expressed genes (DEGS) in P. xylostella treated with cyclosporin C compared to control 24, 48, and 72 h post-treatment, respectively. Thirteen DEGs were commonly expressed at different time intervals in P. xylostella larvae treated with cyclosporin C compared to control. Cyclosporin C treatment induced the down-regulated expression of majority of immune-related genes related to pattern recognition responses, signal modulation, Toll and IMD pathways, antimicrobial peptides and antioxidant responses confirming the ability to suppress immune response of P. xylostella. These results will further improve our knowledge of the infection mechanism and complex biochemical processes involved in interaction between cyclosporin C and insect immune systems.

Transforming waste cellulosic fabric dyed with Reactive Yellow C4GL into value textile by a microwave assisted energy efficient system of color stripping.

A million ton of cotton fabric is wasted during cutting process in garment industry as well as in textile dyeing industry due to faulty dyeing. Color stripping of cotton fabric has become a significant challenge in the textile industry because the harsh chemicals used in chemical stripping processes affects the quality of fabric very badly. Conventional stripping methods lead with severe effects due to prolonged treatment time and high chemical concentrations. Recently, microwave-assisted stripping techniques have been emerged as effective alternatives to improve stripping efficiency. In this research, the developed microwave assisted stripping system is improved by the application of Urea, which is utilized as a microwave absorber to further reduce stripping time, temperature, and chemical concentration kept focus on quality parameters of recycled cotton fabric. This study inspects the efficiency of microwave absorber-assisted alkali hydrolysis and reduction in terms of dye-fabric bond cleavage, chromophores removal, chemical consumption, and processing time and compared with sequential stripping, microwave assisted stripping without absorber and conventional methods. The results indicated that microwave absorber-assisted alkali hydrolysis and reduction achieved 90 % stripping efficiency by using lowest concentrations of chemicals, while sequential stripping yielded a stripping efficiency of 96 %. Similarly, microwave absorber assisted methods resulted in minor loss in tear strength and weight. These outputs highlight the superior performance of microwave absorber-assisted techniques, demonstrating their efficiency, novelty, time-saving nature, and reduced damage compared to other methods.

Hyperspectral imaging combined with GA-SVM for maize variety identification.

The demand for identification of maize varieties has increased dramatically due to the phenomenon of mixed seeds and inferior varieties pretending to be high-quality varieties continuing to occur. It is urgent to solve the problem of efficient and accurate identification of maize varieties. A hyperspectral image acquisition system was used to acquire images of maize seeds. Regions of interest (ROI) with an embryo size of 10 × 10 pixel were extracted, and the average spectral information in the range of 949.43-1709.49 nm was intercepted for the subsequent study in order to eliminate random noise at both ends. Savitzky-Golay (SG) smoothing algorithm and multiple scattering correction (MSC) were used to pretreat the full-band spectrum. The feature wavelengths were screened by successive projection algorithms (SPA), competitive adaptive reweighted sampling (CARS) single screening, and two combinations of CARS-SPA and CARS + SPA, respectively. Support vector machines (SVMs) and models optimized based on genetic algorithm (GA), particle swarm optimization (PSO) were established by using full bands (FB) and feature bands as the model input. The results showed that the MSC-(CARS-SPA)-GA-SVM model had the best performance with 93.00% of the test set accuracy, 8 feature variables, and a running time of 24.45 s. MSC pretreatment can effectively eliminate the scattering effect of spectral data, and the feature wavelengths extracted by CARS-SPA can represent all wavelength information. The study proved that hyperspectral imaging combined with GA-SVM can realize the identification of maize varieties, which provided a theoretical basis for maize variety classification and authenticity identification.

Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid.

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

Radical scavenging potential of spectrophotometric, spectroscopic, microscopic, and EDX observed zinc oxide nanoparticles from leaves, buds, and flowers extract of Bauhinia Variegata Linn: A thorough comparative insight.

The present study incorporated an environment-friendly and cost-efficient green synthesis method for fabricating zinc oxide nanoparticles (ZnO-NPs) using various parts (leaves, buds, and flowers) of Bauhinia Variegate Linn. UV-Spectrophotometric analysis was used to confirm the synthesis of ZnO-NPs, which showed an absorption band within 360-380 nm range. Further techniques like FT-IR spectroscopy and (SEM) scanning electron microscopy equipped with a novel EDX were also included to confirm the synthesis, size, and shape of ZnO-NPs. Results obtained by FT-IR showed that the phytochemicals present in the ethanolic extract successfully acted as a capping agent. SEM micrographs confirmed irregularly shaped nanoparticles with an average size of 70-80 nm. The presence of Zinc and Oxygen peaks in EDX also confirmed the successful synthesis of ZnO nanoparticles. The radical scavenging (antioxidant) potential of prepared nanoparticles was also evaluated by DPPH radical assay. The ZnO-NPs obtained from the ethanolic extract of buds showed the highest %RSA (86%) as compared to the flowers (79%) and leaves (76%). The current study findings showed the versatile morphology of all parts of the plant with significant antioxidant potential, establishing the use of Bauhinia Variegate in biological systems for various biomedical applications. RESEARCH HIGHLIGHTS: A thorough comparative analysis of the radical scavenging power of major parts of the Bauhinia Variegate, which is 1st of its kind. Extensive characterization using UV-Vis spectrophotometry, FT-IR, SEM, and EDX to observe the conformational and morphological changes. Analysis of the reduction potential of leaves, buds, and flowers of a single plant for future directions in green synthesis.

Synergetic effects of sericin and turmeric on burn wound healing in mice.

Burn wounds are one of the most hazardous issues globally. Silkworm produces a protein called sericin. Sericin assists in wound healing by facilitating the proliferation of keratinocytes and fibroblasts while turmeric is potentially helpful in wound healing because of its antioxidant, anti-inflammatory, and anti-infectious activities. The current study aimed to investigate the synergetic and individual effects of turmeric, sericin, and their nanoparticles on burn wounds in mice. The female mice of 2 months of age (each weighing 29-30 g) were arbitrarily distributed in seven groups. Five mice were added to each group. Burn wounds were induced in mice by using a hot metal rod. Burn wounds were evaluated histologically and morphologically. Turmeric nanoparticles substantially improved the wound contraction area as compared to the negative control group and other treatment groups. The serum level of Glutathione (4.9±0.1umol/L), Catalase (6.0±0.2mmol/ml), Glutathione Peroxidase (183.4±5.1U/L), Superoxide dismutase (194.6±5.1 U/ml) were significantly increased in the turmeric nanoparticles (TNPs) group as compared to the negative control (2.8±0.1umol/L, 3.5±0.1mmol/ml, 87.8±3.0U/L, and 92.0±4.8U/ml respectively). The minimum levels of Malondialdehyde (3.8±0.2mmol/L) were noticed in TNPs group contrary to the negative control (7.4±0.2mmol/L). The restoration of the epidermis was also observed to be faster in TNPs group as compared to all other treatment groups. The histopathological analysis also demonstrated the effectiveness of turmeric, sericin, and their nanoparticles. In conclusion, turmeric, sericin, and their nanoparticles are effective in improving the healing process of burn wounds, but TNPs showed the most effective results as compared to all other treatment groups.

Evaluation of irrigation, drinking, and risk indices for water quality parameters of alpine lakes.

Alpine lakes are aquatic ecosystems that maintain and regulate water supply for the downstream streams, rivers, and other reservoirs. This study examined the water characteristics of various alpine lakes in Gilgit-Baltistan, Northern Pakistan. For this purpose, water was sampled and investigated for basic parameters, anions, and cations using the multi-parameter analyzers and atomic absorption spectrophotometer. Physicochemical parameters of alpine lakes were noted under the World Health Organization water guidelines, except for fluoride (F-) and turbidity in 4.3% and 36% of samples, respectively. Water quality index (WQI) classified samples (93%) as excellent and good quality (7%). Results showed maximum chronic daily intake values (0.14 ± 0.01 mg/kg-day) for nitrate (NO3-) and hazard quotient (0.80 ± 0.24) for F- in children via water intake from Upper Kachura and Shausar Lakes, respectively. Statistical analyses of Piper and Gibbs's plots revealed that the water quality is mainly characterized by bedrock geology.

Mechanisms of medicinal, pharmaceutical, and immunomodulatory action of probiotics bacteria and their secondary metabolites against disease management: an overview.

Probiotics or bacteriotherapy is today's hot issue for public entities (Food and Agriculture Organization, and World Health Organization) as well as health and food industries since Metchnikoff and his colleagues hypothesized the correlation between probiotic consumption and human's health. They contribute to the newest and highly efficient arena of promising biotherapeutics. These are usually attractive in biomedical applications such as gut-related diseases like irritable bowel disease, diarrhea, gastrointestinal disorders, fungal infections, various allergies, parasitic and bacterial infections, viral diseases, and intestinal inflammation, and are also worth immunomodulation. The useful impact of probiotics is not limited to gut-related diseases alone. Still, these have proven benefits in various acute and chronic infectious diseases, like cancer, human immunodeficiency virus (HIV) diseases, and high serum cholesterol. Recently, different researchers have paid special attention to investigating biomedical applications of probiotics, but consolidated data regarding bacteriotherapy with a detailed mechanistically applied approach is scarce and controversial. The present article reviews the bio-interface of probiotic strains, mainly (i) why the demand for probiotics?, (ii) the current status of probiotics, (iii) an alternative to antibiotics, (iv) the potential applications towards disease management, (v) probiotics and industrialization, and (vi) futuristic approach.

Impact of automobile exhaust on biochemical and genomorphic characteristics of Mimusops elengi L. growing along roadsides of Lahore city, Pakistan.

Automobile exhaust releases different types of pollutants that are at great risk to the air quality of the environment and incidental distress to the nature of roadside plants. Mimusops elengi L. is an evergreen medicinal tree cultivated along the roadside of Lahore City. This research aimed to investigate physiological, morphological and genomorphic characteristics of M. elengi under the influence of air pollution from vehicles. Healthy and mature leaves were collected from trees on Canal Bank and Mall roads of Lahore as the experimental sites and control sites were 20 km away from the experimental site. Different physiochemical, morphological, air pollution tolerance index (APTI) and molecular analysis for the detection of DNA damage were performed through comet assay. The results demonstrated the mean accumulated Cd, Pb, Cu and Ni heavy metal contents on the leaves were higher than the control plants (1.27, 3.22, 1.32 and 1.46 µg mg-1). APTI of trees was 9.04. Trees in these roads significantly (p < 0.01) had a lower leaf area, petiole length and leaf dry matter content in comparison to control site. Increased comet tail showed that DNA damage was higher for roadside trees than trees in the control area. For tolerance of air pollution, it necessary to check the APTI value for the M. elengi at the polluted road side of Lahore city. For long-term screening, the source and type of pollutants and consistent monitoring of various responses given by the trees should be known.

Pharmacological and immunomodulatory modes of action of medically important phytochemicals against arthritis: A molecular insight.

Arthritis is a common illness that affects joints and it may result in inflammation and pain. Even though arthritis usually affects older people, it can also affect children, adults, and both genders. Numerous arthritic mouse models have been developed but the CIA model of rheumatoid arthritis (RA) has received the most attention. With the use of steroids, DMARDs, and NSAIDs, therapy objectives such as reduced disease incidence and better pain management are achieved. Long-term usage of these therapeutic approaches may have negative side effects. Herbal medications are the source of several medicinal substances. Studies have explored the potential benefits of medicinal plants in treating RA. These benefits include up-regulating antioxidant potential, inhibiting cartilage degradation, down-regulating inflammatory cytokines such as NF-kB, IL-6, and TNF-α, and suppressing oxidative stress. In this review, we systematically discuss the role of traditional medicinal plants in rheumatoid arthritis (RA) disease treatment. The role of different medicinal plants such as Curcuma longa, Syzygium aromaticum, Zingiber officinale and Withania somnifera, against arthritis is discussed in this review.

Synthesis of novel hydrazide Schiff bases with anti-diabetic and anti-hyperlipidemic effects: in-vitro, in-vivo and in-silico approaches.

The increasing global incidence of non-insulin-dependent diabetes mellitus (NIDDM) necessitates innovative therapeutic solutions. This study focuses on the design, synthesis and biological evaluation of Schiff base derivatives from 2-bromo-2-(2-chlorophenyl) acetic acid, particularly hydrazone compounds 4a and 4b. Both in-vitro and in-vivo assays demonstrate these derivatives' strong antidiabetic and anti-hyperlipidemic properties. In a 15-d experiment, we administered 4a and 4b at doses of 2.5 and 5 mg/kg body weight, which effectively improved symptoms of alloxan-induced diabetes in mice. These symptoms included weight loss, increased water consumption and high blood glucose levels. The compounds also normalized abnormal levels of total cholesterol (TC), triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-C), while raising the levels of high-density lipoprotein cholesterol (HDLC). Computational analysis showed that these compounds effectively inhibited the α-glucosidase enzyme by interacting with key catalytic residues, specifically Asp214 and Asp349. These computational results were confirmed through in-vitro tests, where 4a and 4b showed strong α-glucosidase inhibitory activity, with IC50 values of 0.70 ± 0.11 and 10.29 ± 0.30 µM, respectively. These compounds were more effective than the standard drug, acarbose, which had an IC50 value of 873.34 ± 1.67 µM. Mechanistic studies further indicated competitive inhibition, reinforcing the therapeutic potential of 4a and 4b for NIDDM treatment.Communicated by Ramaswamy H. Sarma.

Therapeutic Potential of Aloe vera and Aloe vera-Conjugated Silver Nanoparticles on Mice Exposed to Hexavalent Chromium.

Hexavalent chromium (Cr (VI)) is a hazardous heavy metal that induces hepatotoxicity and nephrotoxicity. Thus, this study was planned to explore the ameliorating capacity of Aloe vera leaf gel extract (AV) and their conjugated silver nanoparticles (AVNP) against Cr (VI) induced hepatotoxicity and renal toxicity. The organ indices, level of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, total protein, and creatinine in blood serum were measured. The histopathological and micrometric analysis of the hepatic and renal tissue sections were studied. The hepatosomatic index was raised significantly (0.098 ± 0.13 g) in Cr treated group. The blood serum level of AST (484 ± 10.7 U/L), ALT (163 ± 5.5 U/L), ALP (336.7 ± 9.5 U/L), MDA (642.3 ± 28.3 U/L), and creatinine (4.0 ± 0.1 mg/dL) were increased significantly, whereas total protein level was declined (2.8 ± 0.3 g/dL) significantly in Cr exposed group. In the histopathological study, necrosis, disturbed hepatic cords, impaired glomeruli, and Bowman's capsule were noted. Micrometric data from the liver and kidney revealed a significant surge in the size of hepatocytes and their nuclei (1188.2 ± 467.7 µ2 and 456.5 ± 205.6 µ2) and CSA of glomeruli and Bowman's capsule (9051.8 ± 249.8 µ2 and 11,835.5 ± 336.7 µ2) in Cr (VI) exposed group, whereas the brush border (10.2 ± 4.0 µ) size declined significantly. The administration of AV and AVNP reduced the oxidative stress induced by Cr (VI).

Exploring the underlying correlation between microbiota, immune system, hormones, and inflammation with breast cancer and the role of probiotics, prebiotics and postbiotics.

According to recent research, bacterial imbalance in the gut microbiota and breast tissue may be linked to breast cancer. It has been discovered that alterations in the makeup and function of different types of bacteria found in the breast and gut may contribute to growth and advancement of breast cancer in several ways. The main role of gut microbiota is to control the metabolism of steroid hormones, such as estrogen, which are important in raising the risk of breast cancer, especially in women going through menopause. On the other hand, because the microbiota can influence mucosal and systemic immune responses, they are linked to the mutual interactions between cancer cells and their local environment in the breast and the gut. In this regard, the current review thoroughly explains the mode of action of probiotics and microbiota to eradicate the malignancy. Furthermore, immunomodulation by microbiota and probiotics is described with pathways of their activity.

Chemoprotective and immunomodulatory potential of Lactobacillus reuteri against cadmium chloride-induced breast cancer in mice.

INTRODUCTION: The current study aimed to investigate the role of probiotic Lactobacillus reuteri for the treatment and prevention of breast cancer. MATERIALS AND METHODS: Breast cancer was induced by using Cadmium Chloride (Cd) (2 mg/kg) in group II. Tamoxifen was administered to group III. Group IV was treated with Lactobacillus reuteri. Group V was treated with Cd for one month and divided into three subgroups including VA, VB, and VC which were treated with tamoxifen, Lactobacillus reuteri, and tamoxifen + Lactobacillus reuteri, respectively. RESULTS: Significantly higher levels of TNF-α (40.9 ± 4.2 pg/mL), IL-6 (28.0 ± 1.5 pg/mL), IL-10 (60.2 ± 2.0 pg/mL), IFN-γ (60.2 ± 2.0 pg/mL), ALAT (167.2 ± 6.2 U/l), ASAT (451.6 ± 13.9 U/l), and MDA (553.8 ± 19.6 U/l) was observed in Cd group. In comparison, significantly lower levels of TNF-α (18.0 ± 1.1 pg/mL), IL-6 (9.4 ± 0.4 pg/mL), IL-10 (20.8 ± 1.1 pg/mL), IFN-γ (20.8 ± 1.1 pg/mL), ALAT (85.2 ± 3.6 U/l), ASAT (185 ± 6.9 U/l), and MDA (246.0 ± 7.5 U/l) were observed in group Cd + Tam + LR. Liver histopathology of the Cd group showed hemorrhage and ductal aberrations. However, mild inflammation and healthier branched ducts were observed in treatment groups. Furthermore, the renal control group showed normal glomerular tufts, chronic inflammation from the Cd group, and relatively healthier glomerulus with mild inflammation in treatment groups. CONCLUSION: Hence, the preventive and anticancerous role of probiotic Lactobacillus reuteri is endorsed by the findings of the current study.