Redefining Chalcone Synthesis: Aldol Adduct Elimination for the Rapid Access to Thienyl Chalcones.

This paper introduces a unique and novel method for synthesizing thienyl chalcones using iron oxide nanoparticles (FeONPs) as a heterogeneous catalyst. It stands out as a rare example in the literature for the synthesis of these chalcones from 1,3-diketones and various aromatic aldehydes. The magnetic FeONPs employed as the catalyst bring several advantages, including their efficiency, affordability, and ecofriendly nature, making them an attractive choice for producing thiophene chalcones. One noteworthy aspect of this methodology is the utilization of mild reaction conditions, which greatly simplify the operational aspects of the reaction. Synthesized chalcones were confirmed through the application of various techniques, proton-NMR, 13C NMR, mass spectrometry, and single-crystal X-ray diffraction analysis. These analyses provide valuable insights into the chemical compositions and structural characteristics of the synthesized compounds. Significantly, this methodology is reported for the first time in the literature, indicating its novelty and contribution to the field of chalcone synthesis.

Polystyrene nanoplastics synergistically exacerbate diclofenac toxicity in embryonic development and the health of adult zebrafish.

In this study, we investigated the possible ecotoxicological effect of co-exposure to polystyrene nanoplastics (PS-NPs) and diclofenac (DCF) in zebrafish (Danio rerio). After six days of exposure, we noticed that the co-exposure to PS-NP (100 µg/L) and DCF (at 50 and 500 µg/L) decreased the hatching rate and increased the mortality rate compared to the control group. Furthermore, we noted that larvae exposed to combined pollutants showed a higher frequency of morphological abnormalities and increased oxidative stress, apoptosis, and lipid peroxidation. In adults, superoxide dismutase and catalase activities were also impaired in the intestine, and the co-exposure groups showed more histopathological alterations. Furthermore, the TNF-α, COX-2, and IL-1ß expressions were significantly upregulated in the adult zebrafish co-exposed to pollutants. Based on these findings, the co-exposure to PS-NPs and DCF has shown an adverse effect on the intestinal region, supporting the notion that PS-NPs synergistically exacerbate DCF toxicity in zebrafish.

Dual Anti-Inflammatory and Anticancer Activity of Novel 1,5-Diaryl Pyrazole Derivatives: Molecular Modeling, Synthesis, In Vitro Activity, and Dynamics Study.

A series of novel 1,5-diaryl pyrazole derivatives targeting the COX enzyme were designed by combined ligand and structure-based approach. The designed molecules were then further subjected to ADMET and molecular docking studies. Out of 34 designed compounds, the top-10 molecules from the computation studies were synthesized, characterized, and evaluated for COX-2 inhibition and anti-cancer activity. Initially, the target compounds were screened for the protein denaturation assay. The results of the top-five molecules T2, T3, T5, T6, and T9 were further subjected to in vitro COX-2 enzymatic assay and anti-cancer activity. As far as COX-2 inhibitory activity is considered, two compounds, T3 and T5, exhibited the half maximum inhibitory concentration (IC50) at 0.781 µM and 0.781 µM respectively. Further, the two compounds T3 and T5, when evaluated for COX-1 inhibition, exhibited excellent inhibitory activity with T3 IC50 of 4.655µM and T5 with IC50 of 5.596 µM. The compound T5 showed more significant human COX-2 inhibition, with a selectivity index of 7.16, when compared with T3, which had a selectivity index of 5.96. Further, in vitro anti-cancer activity was screened against two cancer cell lines in which compounds T2 and T3 were active against A549 cell lines and T6 was active against the HepG2 cell line. Stronger binding energy was found by comparing MM-PBSA simulations with molecular docking, which suggests that compounds T3 and T5 have a better possibility of being effective compounds, in which T5 showed higher binding affinity. The results suggest that these compounds have the potential to develop effective COX-2 inhibitors as anti-cancer agents.

Daidzein ameliorates nonmotor symptoms of manganese-induced Parkinsonism in zebrafish model: Behavioural and biochemical approach.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a prevalent neurodegenerative movement disorder characterized by motor dysfunction. Environmental factors, especially manganese (Mn), contribute significantly to PD. Existing therapies are focused on motor coordination, whereas nonmotor features such as neuropsychiatric symptoms are often neglected. Daidzein (DZ), a phytoestrogen, has piqued interest due to its antioxidant, anti-inflammatory, and anxiolytic properties. Therefore, we anticipate that DZ might be an effective drug to alleviate the nonmotor symptoms of Mn-induced Parkinsonism. EXPERIMENTAL APPROACH: Naïve zebrafish were exposed to 2 mM of Mn for 21 days and intervened with DZ. Nonmotor symptoms such as anxiety, social behaviour, and olfactory function were assessed. Acetylcholinesterase (AChE) activity and antioxidant enzyme status were measured from brain tissue through biochemical assays. Dopamine levels and histology were performed to elucidate neuroprotective mechanism of DZ. KEY RESULTS: DZ exhibited anxiolytic effects in a novel environment and also improved intra and inter fish social behaviour. DZ improved the olfactory function and response to amino acid stimuli in Mn-induced Parkinsonism. DZ reduced brain oxidative stress and AChE activity and prevented neuronal damage. DZ increased DA level in the brain, collectively contributing to neuroprotection. CONCLUSION AND IMPLICATIONS: DZ demonstrated a promising effect on alleviating nonmotor symptoms such as anxiety and olfactory dysfunction, through the mitigation of cellular damage. These findings underscore the therapeutic potential of DZ in addressing nonmotor neurotoxicity induced by heavy metals, particularly in the context of Mn-induced Parkinsonism.

Indole-3 acetic acid induced cardiac hypertrophy in Wistar albino rats.

Indole-3-acetic acid (IAA) is the most widely utilized plant growth regulator. Despite its extensive usage, IAA is often overlooked as an environmental pollutant. Due to its protein-binding nature, it also functions as a uremic toxin, contributing to its association with chronic kidney disease (CKD). While in vitro and epidemiological research have demonstrated this association, the precise impact of IAA on cardiovascular disease in animal models is unknown. The main objective of this study is to conduct a mechanistic analysis of the cardiotoxic effects caused by IAA using male Wistar albino rats as the experimental model. Three different concentrations of IAA (125, 250, 500 mg/kg) were administered for 28 days. The circulating IAA concentration mimicked previously observed levels in CKD patients. The administration of IAA led to a notable augmentation in heart size and heart-to-body weight ratio, indicating cardiac hypertrophy. Echocardiographic assessments supported these observations, revealing myocardial thickening. Biochemical and gene expression analyses further corroborated the cardiotoxic effects of IAA. Dyslipidemia, increased serum c-Troponin-I levels, decreased SOD and CAT levels, and elevated lipid peroxidation in cardiac tissue were identified. Moreover, increased expression of cardiac inflammatory biomarkers, including ANP, BNP, ß-MHC, Col-III, TNF-α, and NF-κB, was also found in the IAA-treated animals. Histopathological analysis confirmed the cardiotoxic nature of IAA, providing additional evidence of its adverse effects on cardiovascular health. These results offer insights into the potential negative impact of IAA on cardiovascular function, and elucidating the underlying mechanisms of its cardiotoxicity.

Neuroprotective potential of pyrazole benzenesulfonamide derivative T1 in targeted intervention against PTZ-induced epilepsy-like condition in in vivo zebrafish model.

Epilepsy is a chronic neurological disease characterized by a persistent susceptibility to seizures. Pharmaco-resistant epilepsies, impacting around 30 % of patients, highlight the urgent need for improved treatments. Neuroinflammation, prevalent in epileptogenic brain regions, is a key player in epilepsy, prompting the search for new mechanistic therapies. Hence, in this study, we explored the anti-inflammatory potential of pyrazole benzenesulfonamide derivative (T1) against pentylenetetrazole (PTZ) induced epilepsy-like conditions in in-vivo zebrafish model. The results from the survival assay showed 79.97 ± 6.65 % at 150 µM of T1 compared to PTZ-group. The results from reactive oxygen species (ROS), apoptosis and histology analysis showed that T1 significantly reduces cellular damage due to oxidative stress in PTZ-exposed zebrafish. The gene expression analysis and neutral red assay results demonstrated a notable reduction in the inflammatory response in zebrafish pre-treated with T1. Subsequently, the open field test unveiled the anti-convulsant activity of T1, particularly at a concentration of 150 µM. Moreover, both RT-PCR and immunohistochemistry findings indicated a concentration-dependent potential of T1, which inhibited COX-2 in zebrafish exposed to PTZ. In summary, T1 protected zebrafish against PTZ-induced neuronal damage, and behavioural changes by mitigating the inflammatory response through the inhibition of COX-2.

Rhodamine B, an organic environmental pollutant induces reproductive toxicity in parental and teratogenicity in F1 generation in vivo.

This study investigated the reproductive toxicity of rhodamine B in zebrafish and its transgenerational effects on the F1 generation. In silico toxicity predictions revealed high toxicity of rhodamine B, mainly targeting pathways associated with the reproductive and endocrine systems. In vivo experiments on zebrafish demonstrated that rhodamine B exposure at a concentration of 1.5 mg/L led to significant impairments in fecundity parameters, particularly affecting females. Histopathological analysis revealed distinct changes in reproductive organs, further confirming the reproductive toxicity of rhodamine B, with females being more susceptible than males. Gene expression studies indicated significant suppression of genes crucial for ovulation in rhodamine B-treated female fish, highlighting hormonal imbalance as a potential mechanism of reproductive toxicity. Furthermore, bioaccumulation studies showed the presence of rhodamine B in both adult fish gonads and F1 generation samples, suggesting transgenerational transfer of the dye. Embryotoxicity studies on F1 generation larvae demonstrated reduced survival rates, lower hatching rates, and increased malformations in groups exposed to rhodamine B. Moreover, rhodamine B induced oxidative stress in F1 generation larvae, as evidenced by elevated levels of reactive oxygen species and altered antioxidant enzyme activity. Neurotoxicity assessments revealed reduced acetylcholinesterase activity, indicating potential neurological impairments in F1 generation larvae. Additionally, locomotory defects and skeletal abnormalities were observed in F1 generation larvae exposed to rhodamine B. This study provides comprehensive evidence of the reproductive toxicity of rhodamine B in adult zebrafish and its transgenerational effects on the F1 generation.

Exploring the Efficacy of Pellitorine as an Antiparasitic Agent Against Argulus: Impacts on Antioxidant Levels and Immune Responses in Goldfish (Carassius auratus).

INTRODUCTION: Argulus spp. infestation is a significant challenge for aquaculture, currently, there are no approved medications available to efficiently manage this parasite. Consequently, mechanical removal of parasites using forceps and natural substances like herbs are being explored as alternative treatment methods. Pellitorine (PLE) is a naturally occurring compound found in several plant species. It is classified as an alkaloid and belongs to the class of compounds known as amides. MATERIALS AND METHODS: This study aimed to evaluate the effectiveness of PLE in preventing Argulus spp. infestations in goldfish (Carassius auratus) and to determine the optimal dosage of PLE for the detachment of Argulus spp. RESULTS: The findings of this study revealed that PLE enhanced the immune response of goldfish by promoting superoxide dismutase (SOD) and catalase (CAT) in Argulus-infected goldfish. Additionally, PLE induces reactive oxygen species (ROS) generation and cellular damage in the Argulus. PLE at a dosage of 5 mg/mL was able to detach 80% of the argulus from goldfish within 12 h. Therapeutic index was found to be 5.99, suggesting that PLE is the safest drug. CONCLUSIONS: Therefore, our findings suggest that PLE can be a suitable and effective treatment option for preventing Argulus infestations in goldfish. The results of this study can guide the use of PLE at an optimal dosage to control Argulus infestation in goldfish.

Application of Bacillus Coagulans as Paraprobiotic Against Acute Hepatopancreatic Necrosis Disease in Shrimp.

Paraprobiotics, known as non-viable or ghost probiotics, have attracted attention for their benefits over live microbial cells. This study was designed to investigate the paraprobiotic effects of heat-killed Bacillus coagulans on the white leg shrimp Litopenaeus vannamei. The paraprobiotic formulation was prepared in three different concentrations including B. coagulans 1 (107 cells g-1 diet), B. coagulans 2 (108 cells g-1 diet), and B. coagulans 3 (109 cells g-1 diet) through heat inactivation method. Preliminary toxicity assessments revealed that post-larvae shrimps (mean weight ± SE: 0.025 ± 0.007 g) treated with B. coagulans 1, 2 and 3 paraprobiotic formulations exhibited no mortality, confirming the non-toxic nature of the formulated diet. In a 90-day feeding trial involving juvenile shrimps (mean weight ± SE: 0.64 ± 0.05 g), growth parameters and feed conversion ratios improved in all experimental groups. Subsequently, these shrimps were challenged with Vibrio parahaemolyticus, revealing that paraprobiotic-fed shrimps exhibited significant survival rate improvements. Oxidative stress-related enzyme activities, such as superoxide dismutase and catalase, increased in paraprobiotic-fed shrimps post-Vibrio challenge, while the challenged control group showed decreased activity (p < 0.001). Nitric oxide levels are also increased in paraprobiotic-treated shrimp, with B. coagulans 3 showing a significant rise in nitric oxide activity (p < 0.001). This study further demonstrated the positive impact of paraprobiotic treatment on digestive enzymes, immune-related parameters (e.g., total hemocyte count, prophenoloxidase, and respiratory burst activity), and overall disease resistance. These findings suggest that B. coagulans paraprobiotics have the potential to enhance antioxidant, antibacterial, and immune-related responses in L. vannamei, making them a valuable addition to shrimp aquaculture.

Exploring the Combined Effect of Exercise and Apigenin on Aluminium-Induced Neurotoxicity in Zebrafish.

Aluminium (AL) is a strong environmental neurotoxin linked to neurodegenerative disorders. Widespread industrial use leads to its presence in water systems, causing bioaccumulation in organisms. This, in turn, results in the bioaccumulation of AL in various organisms. Several studies have highlighted the benefits of enhanced physical activity in combating neurodegenerative diseases. Meanwhile widespread presence of apigenin in aquatic environment has been largely overlooked, in terms of its potential to counter AL-induced neurotoxicity. The combined impact of exercise and apigenin in mitigating the effects of AL-induced neurotoxicity in aquatic animals remains unexplored. Hence, the objective of this study is to determine whether the combined treatment of exercise and apigenin can effectively alleviate the chronic neurotoxicity induced by AL. Zebrafish that were exposed to AL showed behaviours resembling anxiety, increased aggression, unusual swimming pattern, and memory impairment, which are typical features observed in Alzheimer's disease (AD)-like syndrome. Combined treatment of exercise and apigenin protects zebrafish from AL-induced neurotoxicity, which was measured by improvements in memory, reduced anxiety and aggression, and increased levels of antioxidant enzymes and acetylcholinesterase (AChE) activity. Furthermore, AL exposure is associated with increased expression of genes related to neuroinflammation and AD. However, synergistic effect of exercise and apigenin counteract this effect in AL-treated zebrafish. These findings suggest that AL is involved in neurodegenerative diseases in fish, which could affect the integrity of aquatic ecosystem. Hence, there is a strong correlation between enhanced physical activity, apigenin, and the well-being of the ecosystem.

Individual and Simultaneous Electrochemical Detection of Allura Red and Acid Blue 9 in Food Samples Using a Novel La2YCrO6 Double Perovskite Decorated on HLNTs as an Electrocatalyst.

The present study involved the synthesis of La2YCrO6 double perovskites using a sol-gel approach. Additionally, a sonication method was implemented to prepare La2YCrO6 double perovskites decorated on halloysites (La2YCrO6/HLNTs). The La2YCrO6/HLNTs exhibited remarkable conductivity, electrocatalytic activity, and rapid electron transfer. It is imperative to possess these characteristics when overseeing the concurrent identification of Allura red (AR) and acid blue 9 (AB) in food samples. The development of the La2YCrO6/HLNTs was verified through the utilization of diverse approaches for structural and morphological characterization. The electrochemical techniques were employed to evaluate the analytical techniques of La2YCrO6/HLNTs. Impressively, the La2YCrO6/HLNTs demonstrated exceptional sensitivity, yielding the lowest detection limit for AR at 8.99 nM and AB at 5.14 nM. Additionally, the linear concentration range was 10-120 nM (AR and AB). The sensor that was developed exhibited remarkable selectivity, and the feasibility of AR and AB in the food sample was effectively monitored, resulting in satisfactory recoveries.

Sustainable food packaging: Harnessing biowaste of Terminalia catappa L. for chitosan-based biodegradable active films for shrimp storage.

Shrimp, a globally consumed perishable food, faces rapid deterioration during storage and marketing, causing nutritional and economic losses. With a rising environmental consciousness regarding conventional plastic packaging, consumers seek sustainable options. Utilizing natural waste resources for packaging films strengthens the food industry. In this context, we aim to create chitosan-based active films by incorporating Terminalia catappa L. leaves extract (TCE) to enhance barrier properties and extend shrimp shelf life under refrigeration. Incorporation of TCE improves mechanical, microstructural, UV, and moisture barrier properties of the chitosan film due to cross-linking interactions, resulting in robust, foldable packaging film. Active TCE film exhibits high antioxidant property due to polyphenols. These films also exhibited low wettability and showed hydrophobicity than neat CH films which is essential for meat packaging. These biodegradable films offer an eco-friendly end-of-life option when buried in soil. TCE-loaded films effectively control spoilage organisms, prevent biochemical spoilage, and maintain shrimp freshness compared to neat CH films during refrigerated condition. The active TCE film retains sensory attributes better than neat chitosan, aligning with consumer preference. The developed edible and active film from waste sources might offer sustainable, alternative packaging material with a lower carbon footprint than petroleum-based sources.

Impact of butylparaben on ß-cell damage and insulin/PEPCK expression in zebrafish larvae: Protective effects of morin.

Butylparaben (BP), a common chemical preservative in cosmetic and pharmaceutical products, has been known to induce oxidative stress and disrupt endocrine function in humans. In contrast, morin, a flavonoid derived from the Moraceae family, exhibits diverse pharmacological properties, including anti-inflammatory and antioxidant. Despite this, the protective role of morin against oxidative stress-induced damage in pancreatic islets remains unclear. Therefore, in this study, we aimed to investigate the potential protective mechanism of morin against oxidative stress-induced damage caused by BP in zebrafish larvae. To achieve this, we exposed the zebrafish larvae to butylparaben (2.5 mg/L) for 5 days, leading to increased oxidative stress and apoptosis in ß-cells. However, our compelling findings revealed that pretreatment with various concentrations of morin effectively reduced mortality and mitigated apoptosis and lipid peroxidation in ß-cells induced by BP exposure. In addition, zebrafish larvae exposed to BP for 5 days exhibited evident ß-cell damage. However, the pretreatment with morin showed promising effects by promoting ß-cell proliferation and lowering glucose levels. Furthermore, gene expression studies indicated that morin pretreatment normalized PEPCK expression while increasing insulin expression in BP-exposed larvae. In conclusion, our findings highlight the potential of morin as a protective agent against BP-induced ß-cell damage in zebrafish larvae. The observed improvements in oxidative stress, apoptosis, and gene expression patterns support the notion that morin could be further explored as a therapeutic candidate to counteract the detrimental effects of BP exposure on pancreatic ß-cells.

Co-encapsulation and release of apigenin and ascorbic acid in polyelectrolyte multilayer capsules for targeted polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder in women of reproductive age, is linked to hormonal imbalances and oxidative stress. Our study investigates the regenerative potential of apigenin (AP, hydrophobic) and ascorbic acid (AC, hydrophilic) encapsulated within poly (allylamine hydrochloride) and dextran sulfate (PAH/DS) hollow microcapsules for PCOS. These microcapsules, constructed using a layer-by-layer (LbL) assembly, are found to be 4 ± 0.5 µm in size. Our research successfully demonstrates the co-encapsulation of AP and AC in a single PAH/DS system with high encapsulation efficiency followed by successful release at physiological conditions by CLSM investigations. In vitro tests with testosterone-treated CHO cells reveal that the dual-drug-loaded PAH/DS capsules effectively reduce intracellular ROS levels and apoptosis and offering protection. In an in-vivo zebrafish model, these capsules demonstrate active biodistribution to targeted ovaries and reduce testosterone levels through radical scavenging. Histopathological examinations show that the injected dual-drug-loaded PAH/DS microcapsules assist in the development of ovarian follicles in testosterone-treated zebrafish. Hence, this dual-drug-loaded system, capable of co-encapsulating two natural compounds, effectively interacts with ovarian cells, reducing cellular damage and normalizing PCOS conditions.

Role of individual and combined impact of simvastatin and α-TCP in rat calvarial bone defect: An experimental study.

Background: Bone substitutes have been used by doctors for a long time to treat osseous abnormalities. Recently, scientists have been searching for suitable materials to replace bone. Autogenous bone grafts are considered the gold standard for osseous regeneration. However, the limited availability of intraoral sources for grafting material often requires the use of secondary donor sites. Aim: This study aims to compare a control group of standard critical bone defect models treated without any bone transplants to critical size calvarial bony defects treated with various bone replacements, including simvastatin and α-tricalcium phosphate, while analyzing the healing patterns. Materials and Methods: In this investigation, 24 Wistar Albino rats weighing 200-250 g were utilized. The study included four groups, each consisting of six rats. Group I utilized deproteinized bovine xenograft, Group II used Simvastatin (0.1 mg), Group III used Simvastatin (0.1 mg) plus TCP, and Group IV served as the untreated calvarial defects group. After eight weeks of testing, the rats were euthanized, and the calvaria were extracted, decalcified in 20% formic acid, and prepared for histological analysis. Results: The newly produced osseous tissue consisted of woven and lamellar bone, which was observed in all deformities. The mean widths of new bone development in the SIMV with α-TCP (Group III) group after XENO (Group I) and the control group with no graft implantation were 160.33 ± 16.2 µm, 110.59 ± 11.5 µm, and 50.83 ± 5.5 µm, respectively. However, these differences did not show statistical significance (p > 0.05). Conclusions: The quantity and quality of newly produced osseous tissue were comparable in α-TCP with SIMV and XENO. However, inflammatory infiltration was 8more pronounced in regions where SIMV was present alone compared to the combination group.

Brain targeted luteolin-graphene oxide nanoparticle abrogates polyethylene terephthalate induced altered neurological response in zebrafish.

BACKGROUND: Polyethylene terephthalate (PET), a commonly used polymer in various food and plastic bag containers, has raised significant concerns regarding its environmental and human health risks. Despite its prevalent use, the impact of PET exposure on aquatic environments and its potential to induce neurotoxic conditions in species remain poorly understood. Furthermore, the mechanisms underlying amelioration through natural product intervention are not well-explored. In light of these gaps, our study aimed to elucidate the neurotoxic effects of PET in zebrafish through waterborne exposure, and to mitigate its neurological impact using luteolin-graphene oxide nanoparticles. METHODS AND RESULTS: Our investigation revealed that exposure to PET in water triggered adverse effects in zebrafish larvae, particularly in the head region. We observed heightened oxidative stress, lipid peroxidation, and cell death, accompanied by impaired antioxidant defense enzymes. Furthermore, abnormal levels of acetylcholine esterase and nitric oxide in the zebrafish brain indicated cognitive impairment. To address these issues, we explored the potential neuroprotective effects of luteolin-graphene oxide nanoparticles. These nanoparticles demonstrated efficacy in localizing within the zebrafish brain, enhancing their therapeutic impact against PET exposure. Treatment with luteolin-graphene oxide nanoparticles not only mitigated PET-induced neurological alterations but also exhibited a neuroprotective effect. This was evidenced by the regulation of pro-inflammatory cytokine gene expression in the zebrafish brain. Additionally, normalization of locomotory behavior in PET-exposed zebrafish following nanoparticle treatment underscored the potential effectiveness of luteolin-graphene oxide nanoparticles as a treatment against PET-induced neurotoxicity. CONCLUSIONS: In summary, our study emphasizes the urgent need to investigate the environmental and health risks associated with PET. We demonstrate the potential of luteolin-graphene oxide nanoparticles as an effective intervention against PET-induced neurotoxicity in zebrafish.

Herbal Melanin Inhibits Real-Time Cell Proliferation, Downregulates Anti-Apoptotic Proteins and Upregulates Pro-Apoptotic p53 Expression in MDA-MB-231 and HCT-116 Cancer Cell Lines.

Background and Objectives: Cancer is the second-most-important deadly disease in the world, leading to severe socioeconomic consequences and posing a public threat. Consequently, breast and colorectal cancers are significant cancer types that affect women and men more commonly, respectively. Treatment failure or recurrent diseases frequently occur due to resistance, in addition to the side effects of the currently available anticancer agents. Therefore, in this study, herbal melanin anticancer activity was investigated against human breast adenocarcinoma (MDA-MB-231) and human colorectal (HCT 116) cell proliferation and the expression of downregulated anti-apoptotic proteins and upregulated pro-apoptotic p53. Materials and Methods: MDA-MB-231 and HCT 116 cells were monitored for their real-time proliferation properties using Xcelligence. Herbal melanin of various concentrations significantly inhibited MDA-MB-231 and HCT 116 cell proliferation. Then, the expression of proapoptotic and anti-apoptotic proteins such as p53, Bcl-2 and Bcl-xl was studied using Western blotting. Results: The Bcl-2 and Bcl-xl expressions were downregulated, while the p53 expression was upregulated after treatment with herbal melanin. Similarly, the expression of apoptotic proteins such as Bcl-2, Bcl-xl, XIAP, Survivin, Bid, Bax, p53, Cytochrome C, PARP genes and mRNA was studied after herbal melanin treatment using real-time PCR, which revealed the downregulation of Bcl-2, Bcl-xl, XIAP and Survivin and the upregulation of Bid, Bax, p53, Cytochrome C and PARP apoptotic protein expression. Also, caspase 3 and 9 expressions were monitored after the treatment with herbal melanin, which revealed the upregulation of both the MDA-MB-231 and HCT 116 cell types. Conclusions: Overall, herbal melanin can be used as an alternative anticancer agent against the MDA-MB-231 and HCT 116 cell types.

Deacetylepoxyazadiradione ameliorates diabesity in in-vivo zebrafish larval model by influencing the level of regulatory adipokines and oxidative stress.

Obesity and diabetes constitute significant global health issues associated with one another. In contrast to diabetes, which is characterised by oxidative stress that enhances cellular damage and the following complications. Obesity dynamics involve chronic inflammation that promotes insulin resistance and metabolic disruptions. Anti-inflammatory and antioxidant agents, therefore, hold promise for synergistic effects, addressing inflammation and oxidative stress, key factors in managing obesity and diabetes. These agents can be utilized in novel drug delivery approaches. The complex interactions between deacetylepoxyazadiradione (DEA) and zebrafish larva subjected to metabolic impairment due to a high-fat diet (HFD) are examined in this study. The survival assay showed a significantly lower rate (79% survival rate) in the larvae exposed to HFD. Contrastingly, DEA treatment showed significant results with survival rates increasing dose-dependently (84%, 89%, and 94% at concentrations of 50 µM, 100 µM, and 150 µM, respectively). Further investigations revealed that DEA could reduce hyperlipidemic and hyperglycemic conditions in zebrafish larvae. Glucose levels significantly dropped in the DEA treatment, which was associated with a decline in larval weight, lipid accumulation, oxidative stress and apoptosis. Enzyme assays revealed higher antioxidant enzyme concentrations in DEA treated in-vivo larval models, which were associated with reduced expression of pro-inflammatory genes. In conclusion, the results demonstrate that DEA can alleviate oxidative stress and inflammation, effectively easing the diabesity-like state in zebrafish larvae. This offers potential avenues for developing DEA as a valuable drug candidate to manage the intricate diabesity condition.

Unveiling nanotubes-mediated communication: Enterococcus faecalis countering Salmonella ser. Typhi - In vitro and In vivo insights.

Bacteria communicate with each other through contact-dependent and contact-independent mechanisms. While certain contact-dependent mechanisms, such as Type IV and Type VI, have received considerable attention, nanotubes-mediated communication among gut bacteria remains largely unknown. The purpose of this study is to demonstrate the presence of nanotube production in both gut commensal and gut pathogenic bacteria. And also aims to show how Enterococcus faecalis utilizes nanotubes to combat Salmonella ser. Typhi (S. Typhi), a pathogen in the gut. The research findings suggest that the formation of nanotubes is an inherent trait observed in both Gram-positive and Gram-negative bacteria. Interestingly, bacteria generate nanotubes in dynamic environments, biofilms, and even within the gut of zebrafish. These nanotubes develops over time in accordance with the duration of incubation. Furthermore, E. faecalis effectively combats S. Typhi through mechanisms that depend on physical contact rather than indirect methods. Notably, E. faecalis protects zebrafish larvae from S. Typhi infections by reducing reactive oxygen species and cell death, and concurrently boosting the production of antioxidant enzymes. It is hypothesized that E. faecalis might eliminate S. Typhi by transferring toxic metabolites into the pathogen via nanotubes. Gene expression analysis highlights that proinflammatory markers such as TNF-α, IL-1ß, and IL-6 are elevated in Salmonella-infected larvae. However, co-treatment with E. faecalis counters this effect. Findings of this study underscores the significance of nanotubes as a vital machinery for bacterial communication and distribution of virulence factors. Exploring nanotubes-mediated communication at a molecular level could pave the way for innovative therapeutic interventions.

Aquatic Peptide: The Potential Anti-Cancer and Anti-Microbial Activity of GE18 Derived from Pathogenic Fungus Aphanomyces invadans.

Small molecules as well as peptide-based therapeutic approaches have attracted global interest due to their lower or no toxicity in nature, and their potential in addressing several health complications including immune diseases, cardiovascular diseases, metabolic disorders, osteoporosis and cancer. This study proposed a peptide, GE18 of subtilisin-like peptidase from the virulence factor of aquatic pathogenic fungus Aphanomyces invadans, which elicits anti-cancer and anti-microbial activities. To understand the potential GE18 peptide-induced biological effects, an in silico analysis, in vitro (L6 cells) and in vivo toxicity assays (using zebrafish embryo), in vitro anti-cancer assays and anti-microbial assays were performed. The outcomes of the in silico analyses demonstrated that the GE18 peptide has potent anti-cancer and anti-microbial activities. GE18 is non-toxic to in vitro non-cancerous cells and in vivo zebrafish larvae. However, the peptide showed significant anti-cancer properties against MCF-7 cells with an IC50 value of 35.34 µM, at 24 h. Besides the anti-proliferative effect on cancer cells, the peptide exposure does promote the ROS concentration, mitochondrial membrane potential and the subsequent upregulation of anti-cancer genes. On the other hand, GE18 elicits significant anti-microbial activity against P. aeruginosa, wherein GE18 significantly inhibits bacterial biofilm formation. Since the peptide has positively charged amino acid residues, it targets the cell membrane, as is evident in the FESEM analysis. Based on these outcomes, it is possible that the GE18 peptide is a significant anti-cancer and anti-microbial molecule.