Impaired macrophage polarization is one of the primary factors that hinders the healing of chronic wounds. A bioinspired hydrogel comprising amidated pectin (AmPT) and dialdehyde carboxymethylcellulose (DCMC) reinforced with honey was reported for wound healing. Pectin was obtained from orange peels via microwave-assisted extraction and further subjected to amidation. The hydrogels were constructed by the Schiff base reaction between the amino groups of AmPT and the aldehyde groups of DCMC. The hydrogels incorporated with the highest honey content, i.e., HH3 hydrogel, exhibited higher thermal stability, tensile strength, and anti-inflammatory and antioxidant properties. A controlled release drug profile for curcumin was evidenced in the colorectum from the HH3@Cur hydrogel, and the release kinetics indicated the anomalous nature of release. An enhanced migration and proliferation of 3T3 fibroblasts was marked for HH3@Cur. The wound closure was noted at almost 92% for the HH3@Cur hydrogel after 24 h. The q-PCR analysis revealed that the expressions of IL-4, IL-13, and PPAR-γ were upregulated in the HH3@Cur-treated group, indicating that it efficiently promoted macrophage transition from pro-inflammatory M1 to anti-inflammatory M2 phenotypes associated with improved wound repair. Furthermore, the HH3@Cur hydrogel was explored for microtissue formation and wound healing application using a zebrafish model, which aligned with in vitro data. Herein, by 16 dpw, the wound closure rate marked to 92.8% for HH3@Cur hydrogel in comparison to the control group (71.5%), and the mean mRNA expressions of IL-4, IL-13, and PPAR-γ were upregulated accordingly. Overall, the results indicated that HH3@Cur hydrogel ameliorates wound healing by influencing the expression of biomarkers related to inflammation, macrophage polarization, and angiogenesis.

Tunneling nanotubes (TNTs) are nano-scale intracellular conduits facilitating the transfer of cellular content. Intercellular communication between cancer cells via TNTs promotes invasion and metastasis. Given the important role of TNTs and macrophages in cancer, the role of macrophage-induced TNTs in the co-delivery of metformin (MET) and the chemotherapeutic drug doxorubicin (DOX) in mediating drug resistance is not fully understood. In this study, the inhibition of TNT-mediated breast cancer progression was mechanistically explored through DOX/MET co-delivery. For cargo delivery, the co-drugs were loaded onto gelatin and gum acacia. The DOX/MET co-loaded nanohydrogel induced the most substantial reduction in cell viability in MCF-7 breast cancer cells. The combination of DOX-MET resulted in the robust activation of caspase-3, indicating the enhanced execution of apoptosis. Upon internalization and lysosomal release, MET activates AMPK signaling, which in turn suppresses the PI3K/AKT/mTOR axis and inhibits TNT formation, thereby blocking intercellular communication. Concurrently, DOX localizes to the nucleus, where it disrupts DNA replication and directly induces cytotoxicity. This combined approach not only targets proliferative capacity but also dismantles cellular networking mechanisms. Overall, the results of this study endorse that this combined therapeutic strategy might offer enhanced efficacy in limiting breast cancer progression and metastasis through the inhibition of TNTs.

Saffron (Crocus sativus L.) is one of the world's most valuable spices, renowned for its distinctive aroma, flavor, and pharmacological properties derived from apocarotenoids such as crocin, picrocrocin, and safranal, which accumulate in the stigmas during flower development. Despite their economic and medicinal importance, the molecular regulation of apocarotenoid biosynthesis across floral developmental stages remains poorly understood, particularly at the proteomic level. To address this gap, we applied an LC-MS/MS-based proteomic approach combined with bioinformatic and structural analyses to characterize stage-specific protein expression across five developmental stages: corm with floral shoot buds (A1), flower inside the sheath (S1), just outside the sheath (S2), flower at unopened state (S3), and flower at opened state (S4). Differential abundance analysis, gene ontology enrichment, STRING-based protein-protein interaction networks, KEGG pathway mapping, and structural modeling identified 57 developmentally regulated proteins linked to stigma differentiation and apocarotenoid metabolism. Stage-specific protein sets comprising 128 (A1), 44 (S1), 38 (S2), 29 (S3), and 29 (S4) proteins were selected using stringent statistical thresholds and validated through Limma-based differential expression analysis. Key enzymes, including PSY2, CCD2, ALDH2B4, and UGT707B1, emerged as central regulators of apocarotenoid biosynthesis during floral maturation. Overall, this study provides a comprehensive proteomic framework underlying stigma development and apocarotenoid accumulation in saffron, offering valuable molecular targets for improving metabolite yield and quality. The data supporting this study have been deposited in the ProteomeXchange repository under the identifier PXD076029.

The development of tumor-selective boron carriers is critical for advancing targeted cancer therapies. In this study, we report the design, synthesis, and characterization of four ortho-carborane-appended symmetrical trimers, Ph-6-CB, Ph-9-CB, Tz-6-CB, and Tz-9-CB, to systematically compare the influence of central-core electronics and peripheral carborane density on photophysical and biological properties. Photophysical studies revealed that all four conjugates exhibit strong π-π* absorption in the 328-335 nm region; the triazine-cored derivatives show a modest blue shift relative to their phenylene analogs. Phenylene derivatives retain higher fluorescence quantum yields than their triazine analogs. Qualitative DFT analysis displays smaller HOMO-LUMO separations and substantially higher computed electrophilicity indices for triazine analogs than the phenylene analogs. Preliminary in vitro cytotoxicity assays against MDA-MB-231 triple-negative breast cancer cells and NIH/3T3 mouse embryo fibroblasts revealed higher potency and greater cancer selectivity of triazine derivatives than their phenylene counterparts. Tz-9-CB emerged as the lead candidate, with an IC50 of 6 µM against MDA-MB-231 cells and a selectivity index of 13 relative to NIH/3T3 fibroblasts. Mechanistic studies, including Live/Dead fluorescence imaging and caspase-3 activation assays, confirmed that Tz-9-CB induces cell death primarily through apoptosis. These findings highlight the potential of triazine-cored, carborane-rich dendrimers as selective scaffolds for boron-based cancer therapeutics.

Hypothyroidism has been associated with cognitive disorders and high risk of neurodegenerative disorders like Alzheimer's disease (AD), which is caused by amyloid-β (Aβ) accumulation in brain. The aim of the study is to examine the therapeutic ability of triiodothyronine (T 3 ) and curcumin in regulating two key extracellular matrix proteins (ECM), collagen IV and collagen VI in brain since both drugs have neuroprotective and anti-fibrotic effects. The study further explored the possible role of signaling molecules such as transforming growth factor β1 (TGFβ1) and specificity protein 1 (Sp1) in regulating the effects of T 3 and curcumin on Aβ accumulation and ECM protein expression. Experiment was carried on Balb/c mouse model by inducing hypothyroidism with 0.05% PTU followed by treatment of T3, curcumin and a combination of both. The study revealed a significant increase in the expression of collagen IV and VI, along with elevated levels of TGFβ1 and Sp1 signalling proteins, in hypothyroid conditions in response to increased Aβ expression in both the cortex and hippocampus. Western blot and RT-PCR analysis showed that T 3 and curcumin treatment downregulate the levels of ECM proteins, the APP gene, Aβ protein, and the signaling factors. The study found that T3 and curcumin treatment downregulates the collagen IV and VI expression by negatively regulating TGFβ1 and Sp1 when expression of APP and Aβ are low. T 3 and coadministration of T 3 with curcumin more effectively regulate thyroid function and ECM protein expression in both the cortex and hippocampus. Whereas curcumin alone exhibits limited impacts under the experimental conditions in our study, this may due to bioavailability, dosage or treatment duration which need to further investigation. Our results indicate a novel therapeutic approach for understanding Aβ pathology associated with hypothyroidism, emphasizing the potential association between thyroid hormone and nature-based compounds, such as curcumin, in modulating ECM dynamics and neuroprotection.

Background: Extracellular vesicles, particularly exosomes, play a crucial role in cell–cell communication and as carriers of biomarkers. However, their use in clinical settings is limited due to a lack of standardized isolation and characterization. Ultracentrifugation (UC) is considered a gold standard for exosome isolation but presents several limitations. Size-exclusion chromatography (SEC) has recently gained attention as a superior method, which offers better yield, purity, and protection of exosome physical properties. This study focused on optimizing the SEC method for isolation of exosomes from seminal plasma and comparing yield, quality, and proteome profiles with those obtained by UC. Methods: In this SEC method, seminal plasma (0.5 mL) was loaded onto a SEC column and collected in 13 fractions of 0.4 mL each. The physical and molecular characterization of exosomes was carried out using a ZetaView analyzer and Western blot, respectively. Further, SEC-isolated exosomes were used for proteomic profiling and functional bioinformatic analysis. Results: The second and third fractions had the highest concentration of exosomes with uniform size and strong expression of exosome markers. Also, comparative proteomic analysis identified 3315 proteins in SEC-isolated exosomes and 931 in UC-isolated exosomes, with 709 proteins in common. SEC-isolated exosomes showed greater overlap with Vesiclepedia’s and ExoCarta’s top 100 lists than UC-isolated exosomes (Vesiclepedia: 91 vs. 77 proteins, ExoCarta: 94 vs. 79). Proteins from SEC- and UC-isolated exosomes showed similar enrichment profiles across all three gene ontology categories. Conclusions: Overall, this optimized SEC protocol is a reliable alternative method to isolate seminal exosomes with high purity, supporting its potential applications in clinical and basic research.

Spermatozoa are highly specialized cells, and any alterations in their protein profiles may affect their function and fertilizing ability. In spermatozoa, which are transcriptionally and translationally inactive, molecular chaperones, particularly heat shock proteins, play crucial roles in maintaining redox balance and preserving protein integrity. Post-translational modifications, particularly lysine acetylation, influence chaperone function and are lately being recognized in the pathophysiology of male infertility. To assess the impact of lysine acetylation on sperm chaperone proteins in idiopathic infertile patients (IIP) compared to fertile donors (FD), we performed immunoprecipitation coupled with liquid chromatography and tandam mass spectroscpy analysis of lysine acetylated sperm proteins from both groups. Proteomic analysis revealed 2988 acetylated proteins, comprising 26 chaperone proteins that were differentially expressed, with four upregulated and nine downregulated in the IIP group. Functional analyses demonstrated enrichment of these proteins in protein folding, spermatogenesis, and response to oxidative stress. CytoHubba analysis reported key HSP70 family members, HSPA2, HSPA4, and HSPA1A as central hub proteins in protein-protein interaction networks. STRING and Ingenuity Pathway Analysis (IPA) network analyses further highlighted the central regulatory roles of these chaperones, with HSPA2 emerging as a key hub protein based on friendship analysis. Western blot validation revealed hypoacetylation and downregulation of HSPA2 in spermatozoa from the IIP group, accompanied by elevated levels of 4-Hydroxynonenal (4-HNE), indicating a link between redox imbalance and altered lysine acetylation in chaperone proteins. Additionally, intense aniline blue staining of sperm nuclei in the IIP group suggested aberrant spermiogenesis. Considering HSPA2 ' s well-documented involvement in sperm maturation and oocyte recognition, its diminished acetylation and expression may not only act as a potential biomarker but also contribute mechanistically to the development of idiopathic male infertility. This study underscores the significance of lysine acetylation in HSPA2 in regulating chaperone function and highlights its diagnostic and therapeutic potential in unexplained male infertility.

Bile salts (BS) are naturally occurring steroidal biosurfactants. The ease of functionalization of BSs has boosted their use as inexpensive building blocks for the fabrication of a broad set of value-added soft functional materials. In the present work, three fluorescent bile acid (FBA) derivatives have been synthesized by conjugating anthracene at the side chain of lithocholic acid, deoxycholic acid, and cholic acid to understand the effect of the nature of the steroid nucleus on their physicochemical properties. In an aqueous medium, the FBAs showed a strong supramolecular aggregation propensity, even in the micromolar concentration range, which is in contrast to their BS analogues that form micelles mostly in the millimolar range. The FBA aggregation leads to a prearranged geometry in the ground state with a favorable orientation of anthracene units for excimer formation on excitation, leading to supramolecular aggregation-induced enhanced emission (AIEE). A detailed investigation reveals the pivotal role of the steroidal skeleton in their aggregation propensity and optical behavior. The FBA assemblies, with ordered structures plus anthracene being a part of their building blocks, are endowed with interesting properties different from those in dilute organic media, which makes them extremely attractive for diverse applications, e.g., as potential drug carriers owing to their ability to serve as efficient hosts for the protective encapsulation of hydrophobic guests; as membrane probes and bioimaging agents due to their efficient membrane permeability and cell-imaging ability; and as system probes because of their remarkable sensitivity toward the aggregation process of natural bile salts in the aqueous medium. Therefore, the present study not only enhances the fundamental understanding of this unique class of amphiphiles but also opens new prospects in tailoring novel self-assembled soft functional materials. Moreover, it offers a benchmark for developing BS-based fluorescent derivatives with unique photophysical characteristics for applications as potential bioprobes.

The aryl hydrocarbon receptor (AhR) is a key protein involved in numerous metabolic processes and signaling pathways across various cell types. Part of the basic helix-loop-helix (bHLH) transcription factor family, AhR contains a central PER-ARNT-SIM (PAS) domain crucial for binding ligands. When AhR binds to xenobiotic (toxic) substances, it becomes activated and influences a range of biological functions, such as cell proliferation, apoptosis, adhesion, differentiation, and the regulation of other transcription factors. However, the binding of certain ligands can also trigger harmful effects, contributing to disease development. Given that AhR serves as a link between the body and the external environment, understanding its response to environmental toxins, xenobiotics, and carcinogens is vital. Yet, studying AhR’s role in toxicology, physiology, and disease is challenging due to limited structural data. To overcome this, computational molecular modeling techniques like molecular docking, molecular dynamics (MD) simulations, and homology modeling have become crucial tools in AhR research. These methods provide valuable insights into how AhR is activated, its modulatory effects, and help complement experimental studies. This review highlights the use of in silico approaches to better understand AhR activation, its role in biological activities, disease progression, and potential therapeutic applications.

Ferroptosis, a recently identified form of regulated cell death, has emerged as a key player in the pathophysiology of various disorders, including male reproductive dysfunction. This review explores the interplay of ferroptosis with male reproductive health, focusing on the molecular mechanisms involved. Global male reproductive health has been deteriorating due to a combination of genetic, environmental, and lifestyle factors, including oxidative stress, reactive oxygen species (ROS), epigenetic alterations, and posttranslational modifications (PTMs). Ferroptosis is characterized by iron overload and lipid peroxidation, leading to testicular damage and impaired spermatogenesis, thus contributing to male infertility. While iron plays an essential role in maintaining spermatogenesis and testosterone production, its overload induces oxidative stress, ROS accumulation, and testicular ferroptosis, which disrupts normal reproductive function. Factors such as failure of antioxidant defense systems, exposure to xenobiotics (e.g., arsenite, cadmium, phthalates, bisphenol A, PM2.5), and alterations in ferroptosis-related genes (FRGs) further exacerbate testicular dysfunction. This review examines the critical role of lipid, iron, and glutathione metabolic pathways in ferroptosis induction, the effects of environmental xenobiotics on testicular health, and the potential therapeutic benefits of ferroptosis inhibitors in treating male infertility.

Idiopathic male infertility (IMI), which accounts for nearly 50% of male infertility cases, remains a major clinical challenge due to the inability of standard semen analysis to reveal underlying molecular defects. Post-translational modifications such as lysine acetylation are increasingly recognized as key regulators of sperm function, affecting antioxidant defense, energy metabolism, and spermatogenesis. In this study, global acetyl-proteomic profiling of spermatozoa from idiopathic infertile patients (IIP) and fertile donors (FD) was performed using immunoprecipitation-based enrichment followed by high-resolution LC-MS/MS. Bioinformatics analyses, including STRING, Cytoscape, and Ingenuity Pathway Analysis (IPA), identified 718 differentially acetylated proteins (DAPs), with significant enrichment in pathways related to redox homeostasis, molecular transport, glycolysis, and mitochondrial metabolism. Hub proteins such as SOD1, PARK7, and PRKACA emerged as key regulators linking oxidative stress with defective motility and impaired sperm physiology. Western blot validation confirmed the downregulation of these hub proteins in IIP, supporting their role in redox imbalance and mitochondrial dysfunction. Our findings highlight dysregulated lysine acetylation as a defining molecular feature of IMI and suggest that targeting acetylation-associated pathways may provide novel diagnostic biomarkers and therapeutic strategies to improve sperm function and male reproductive outcomes.

Background:The association between Vitamin D Receptor (VDR) polymorphisms and different cancers has attracted growing attention; nonetheless, the function of these genetic variants in tobacco-related oral cancer remains little comprehended. This review assesses and integrates research concerning the influence of VDR gene variants on the development of tobacco-related oral cancer, emphasizing genetic underpinnings of individual vulnerability and possible tailored preventative approaches. Materials and methods:The search strategy for this systematic review and meta-analysis was devised to comprehensively identify relevant studies from diverse sources. The investigation included three primary components: the VDR gene, oral cancer, and tobacco. The data from the papers included in the study were independently retrieved by two reviewers. The incidence was evaluated as an odds ratio (OR) with 95% confidence interval (95% CI) using SPSS software. Results:A preliminary search of biomedical electronic research databases (PubMed, Web of Science, Scopus, Embase, and the Cochrane Library) yielded 60,345 papers. After multi-phase exclusions, five studies met the inclusion criteria. The meta-analysis highlights interactions between genetic polymorphisms, smoking, aging, and oral health risks. The CYP24A1 (rs2296241) heterozygote genotype significantly reduces oral cancer risk (OR = 0.281, P = 0.00001). Variants rs1544410 and rs2228570 influence oral health outcomes. The rs2239185 TT (OR = 2.68, P = 0.009) and rs7975232 CC (OR = 2.25, P = 0.026) increase oral lichen planus risk. Older age is significantly linked to OSCC risk (P = 0.001). Conclusion:This research underscores the role of VDR gene variants in tobacco-related oral cancer. Further studies are essential to validate findings and explore underlying mechanisms. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/view/CRD42024587292, identifier: CRD42024587292.

Two triazine-cored BODIPY trimers (Compounds 6 and 12) were synthesized and well characterized using H-1 NMR, C-13 NMR, B-11 NMR, F-19 NMR, FT-IR, and high-resolution mass spectral analysis. The photophysical, computational, and in vitro anticancer studies of the synthesized compounds were comprehensively evaluated along with previously reported phenylene-BODIPY trimer (Compound 1). The photophysical studies indicated that the triazine-cored BODIPY trimers exhibited a slight bathochromic shift compared to the phenylene-cored trimer. Density functional theory (DFT) calculations suggest that the order of stability of the BODIPY trimers was 1 > 6 > 12. The anticancer efficacy of the BODIPY trimers was investigated against human breast adenocarcinomas cell line MDA-MB-231 and mouse embryo fibroblast cell line NIH/3T3 through in vitro cytotoxicity assay. All the BODIPY trimers exhibited elevated cytotoxicity towards cancer cells while displaying lesser cytotoxicity towards normal cells. Compound 6 showed the highest cell death potential with an IC50 value of 27.02 mu M, which is twice higher than that of the chemotherapeutic drug cisplatin. The triazine-cored BODIPY trimers demonstrated superior cytotoxicity against cancer cells in comparison to their phenylene-cored counterparts. The enhanced cytotoxicity of the triazine-cored trimers suggests that the triazine core plays a crucial role in enhancing their therapeutic efficacy. This result underscores the potential of triazine-cored BODIPY trimers as promising anticancer agents.

Two carborane-functionalized thiocarbohydrazone derivatives, TCH- m -CB and TCH- p -CB, were synthesized and well-characterized. The anticancer potential of these compounds was evaluated in vitro against the MCF-7 human breast cancer cell line and NIH/3T3 mouse embryo fibroblast cell line. The cytotoxicity study shows that the meta-carborane derivative, TCH- m -CB, shows higher cytotoxicity toward cancer cells with an IC50 value of 36.96 mu M. The caspase-3 activity assays confirmed that both compounds induce cell death through apoptosis. The computational DFT studies indicated a higher HOMO-LUMO energy gap for TCH- m -CB (3.870 eV) compared to TCH- p -CB (2.811 eV), indicating a higher stability of the meta-carborane derivative, TCH- m -CB, in the ground state. The molecular docking study shows that the thiocarbohydrazone derivatives of carboranes exhibit stronger binding affinities to key cancer-related protein targets (Er alpha, Topo II alpha, and PARP-1) than the reference drug, doxorubicin. The in silico analysis of the ADMET properties of thiocarbohydrazone derivatives of carboranes also exhibits highly promising drug-like properties as compared to the reference drug doxorubicin. Overall, the results indicate that the carborane-functionalized thiocarbohydrazone derivatives have the potential to be effective anticancer agents.

Cancer remains the leading cause of death worldwide. Despite decades of continuous research, limitations persist in existing therapeutic approaches. Conventional strategies such as surgery, chemotherapy, and radiotherapy, though advanced, face challenges including poor bioavailability, toxic side effects, inadequate targeting of cancer cells, and limited survival benefits. The major issue lies in the inability of improved drug formulations to effectively reach cancer cells. Emerging approaches such as photodynamic therapy (PDT) and immunotherapy have shown greater promise, offering reduced side effects and higher treatment efficiency compared to traditional methods. Various natural and synthetic nanocarriers, including exosomes, liposomes, solid lipid nanoparticles (SLNs) and micelles have been explored as drug delivery vehicles in these therapies. Among them, exosomes, being natural secretory vesicles, have shown unique potential as independent delivery systems. However, challenges and limitations remain in their application for precise cancer targeting. A combinational strategy, integrating exosomes with other lipid-based drug delivery systems (LBDDS), while preserving their intrinsic properties and engineering their surface to carry photosensitizers (PS) or immune modulators, could overcome these barriers. Such well-designed natural cargos may enhance therapeutic efficacy, modulate the tumor microenvironment, and address current shortcomings in cancer therapy. This review highlights the individual applications of PDT and immunotherapy using exosomes and LBDDS, and explores their potential synergistic use for more effective and targeted cancer treatment.

In this study, a series of 18 3‐styryl‐2 H ‐chromene‐fused maleimide derivatives were synthesized and characterized by using 1 H NMR, 13 C NMR, HRMS, and FT‐IR spectroscopic techniques. Additionally, the crystal structure of compound 16k was confirmed by single‐crystal X‐ray diffraction analysis. In silico molecular docking studies were formed against bacterial strains Escherichia coli ( E. coli ) and Enterococcus faecalis ( E. faecalis ), revealing that the compound 16e exhibited the strongest binding affinities, with binding scores of −8.6 kCal/mol ( E. coli ) and −9.7 kCal/mol ( E. faecalis ). In vitro antibacterial evaluation further demonstrated that compound 16e , showing excellent efficacy, displayed a Zone of inhibition (ZI) of 15 and 18 mm against E. coli and E. faecalis , respectively, and a minimum inhibitory concentration (MIC) of 62.5 and 31.25 µg/mL against E. coli and E. faecalis , which were comparable to the standard antibiotic Amoxicillin. Furthermore, virtual ADMET analysis was conducted to assess the pharmacokinetic profiles of synthesized compounds. The results suggested that most of the derivatives exhibited favorable bioavailability and drug‐like parameters. Spectroscopic investigation revealed that the absorption maxima and optical densities of compounds were influenced by the nature and position of the substituents. Specifically, an electron‐withdrawing group at the distant positions enhanced conjugation, leading to red‐shifted absorption maxima.

Current study aims to evaluate the impact of trace metal pollution on oxidative stress of selected fish species (Liza parsia and Arius arius) from the Brahmani-Baitarani estuary. Notably, significant alterations in water parameters (temperature, pH, salinity and selected heavy metals) were observed as part of this study. Metal accumulation followed the order: muscle > gills > liver for Cu, while for Cr, the order was liver > gills > muscle. Antioxidant enzyme activity such as superoxide dismutase, glutathione-S-transferase and catalase ranged between 41.51 +/- 2.80 to 364.05 +/- 0.26 units/g Fwt, 0.74 +/- 1.98 to 29.84 +/- 2.54 mu M/min/mg protein and 2.0 +/- 0.5 to 17.0 +/- 1.2OD/ min/g Fwt respectively. The protein content ranged from 7 to 22%. Positive significant relationship (p<0.05) of GST and CAT were observed in A. arius with water temperature and salinity unlike L. parsia. The accumulation of Cu and Cr in the muscles exceeded the permissible limits leading to physiological stress in fishes. ANOVA results revealed significant variation (p<0.05) between stations and seasons with respect to Cu and Cr levels in the muscle, gills and liver of both L. parsia and A. arius species. Regular monitoring is crucial in order to maintain the daily intake level of fishes addressing SDG 14.

A new series of 2H-chromene-based hydrazones (10 a-w, 12 a-d, and 14 a-d) were efficiently synthesized by the reaction of substituted 2H-chromene aldehydes (8 a-w) with various hydrazines (9, 11, and 13) in absolute ethanol under microwave irradiation as well as by lemon juice mediated conventional heating. The structures of synthesized target molecules were identified by spectroscopic analysis methods (H-1 NMR, C-13 NMR, FT-IR, and HRMS). The in vitro anticancer activity of the new 2H-chromene-based hydrazones were evaluated on the three breast cancer cell lines (MCF-7, MDA MB-231, and MDA MB-468) by MTT assay. Among these synthesized compounds, 10 r and 12 b exhibited the most potent antiproliferative activities with IC50 values at 9.12 +/- 0.45 mu M and 10.71 +/- 0.67 mu M respectively, against MCF-7 cell. Flowcytometric analysis revealed that these two potent compounds, 10 r and 12 b arrested the cell cycle at the G2/M phase and induced apoptosis of proteins in a dose-dependent manner. It was further confirmed by Hoechst staining and Annexin V-FITC assay. Additionally, compounds 10 r and 12 b were examined by in silico molecular docking, which revealed that compound 10 r displayed excellent binding affinity energy of around -10 kcal/mol with human HER2 receptor. Also, the ADME studies validated the hybrid compounds showing promising physicochemical, pharmacokinetic, and drug-like attributes. Broadly, these results underscored the potential of 2H-chromene-based hydrazone derivatives as promising anticancer agents.

In this study, we report the cardioprotective effect of the glycerol monooleate (GMO) based nanocurcumin in both in vitro and in vivo conditions under a hyperthyroid state. The heart is one of the primary target organs sensitive to the action of thyroid hormone, and slight variations in the thyroid hormone serum concentrations result in measurable changes in cardiac performance. Hyperthyroidism-induced hypermetabolism is associated with oxidative stress and is an important mechanism responsible for the progression of heart failure. Curcumin has been known to play a protective role against oxidative stress-related diseases like Alzheimer's, asthma, and aging due to its antioxidant properties. Nevertheless, its potent biological activity has been hindered due to its poor bioavailability. To overcome this drawback, a GMO-based biodegradable nanoparticle (NP) formulation loaded with curcumin has been developed, and the protective effect of curcumin-loaded NPs was compared against the native drug. Oxidative stress parameters like reactive oxygen species (ROS) release, change in mitochondrial membrane permeability, lipid peroxidation (LPx), lactate dehydrogenase (LDH) release, and the activity and protein expression of the endogenous antioxidant enzymes like superoxide dismutase, catalase (CAT) and glutathione peroxidase were evaluated. The results from in vitro showed that curcumin-loaded NPs showed better DPPH and NO radical scavenging activity than native curcumin in a concentrations range of 2.5-20 µM. It was also observed that the nanoparticulate curcumin was comparatively more effective than native curcumin in protecting against ROS-induced membrane damage by reducing LPx and LDH leakage at low concentrations of 5-10 µM. Further, curcumin NPs performed better in facilitating the activities of antioxidant enzymes under in vitro and in vivo conditions with respect to time and concentrations, resulting in reduced cellular ROS levels. In this scenario, we anticipate that curcumin-loaded NPs can serve as a better antioxidant than its native counterpart in protecting the heart from oxidative stress-related diseases.

Diabetes mellitus is a heterogeneous group of metabolic disorders characterized by persistent hyperglycaemia and becoming a serious threat to mankind health in all parts of the world. Production of reactive oxygen species and disturbed capacity of antioxidant defence have been reported for enhanced production of free radicals in diabetic subjects. As oxidative stress is found to be a central event in the development of diabetic complications, hence antioxidants may play an important role in the improvement of diabetes and its associated complications. Currently there has been an increased interest globally to identify antioxidant compounds that are pharmacologically potent and have low or no side effects. Phytochemicals and metabolites from mangrove plants are reported to exhibit strong antioxidant properties in terms of both enzymatic and non-enzymatic activities. Recent researches have also revealed that a number of mangrove plants have shown antidiabetic activities attributed to their unique metabolites such as flavonoids, triterpenoids, limonoids and polysaccharides. Thus, mangrove plants can be of great use in tackling diabetic and its associated oxidative stress mediated complications. The present review highlights a relation between oxidative stress and diabetes and the role of mangrove plants in alleviating diabetes, in general, and oxidative stress mediated diabetic complications, in particular.