Assessment of heavy metal levels in polyculture fish farms and their aquatic ecosystems: an integrative study addressing environmental and human health risks associated with dam water usage.

This study examines the levels of heavy metals in polyculture fish (Labeo rohita, Cyprinus carpio, and Catla catla), water, and sediment in Tanda Dam, Kohat, Pakistan, aiming to understand environmental and health risks. Samples of fish, water, and sediment were collected from 3 fish farms, and heavy metal concentrations were measured using a Flame Atomic Absorption Spectrophotometer (AAS). Results reveal that C. catla exhibited significantly higher (p < 0.05) levels of Zn than other fish species. Conversely, C. carpio showed significantly higher (p < 0.05) concentrations of Pb, Cd, Cr, Mn, Cu, As, and Ni than other species. The heavy metal hierarchy in C. carpio was found to be Zn > Cu > Pb > Cr > Cd > Mn > As > Ni. While heavy metal levels in L. rohita and C. catla generally fell within reference ranges, exceptions were noted for Zn, Pb, and Cd. Conversely, in C. carpio, all metals exceeded reference ranges except for Cu and Ni. Principal Component Analysis (PCA) indicated a close relationship between water and sediment. Additionally, cluster analysis suggested that C. catla formed a distinct cluster from L. rohita and C. carpio, implying different responses to the environment. Despite concerns raised by the Geoaccumulation Index (Igeo) and Contamination Factor (CF), particularly for Cd, which exhibited a high CF. Furthermore, Hazard Index (HI) values for all three fish species were below 1, suggesting low health risks. However, elevated Igeo and CF values for Cd suggest significant pollution originating from anthropogenic sources. This study underscores the importance of monitoring heavy metals in water for both environmental preservation and human health protection. Future research efforts should prioritize pollution control measures to ensure ecosystem and public health safety.

Heavy Metal Concentrations in Water, Sediment, and Fish Species in Chashma Barrage, Indus River: A Comprehensive Health Risk Assessment.

The increasing levels of heavy metals in aquatic environments, driven by human activities, pose a critical threat to ecosystems' overall health and sustainability. This study investigates the bioaccumulation of heavy metals (Pb, Cu, Cr, and Cd) in water, sediment, and three fish species (Catla catla, Labeo rohita, Cirrhinus mrigala) of different feeding zones within Chashma Barrage, located in the Mianwali district of Punjab, Pakistan, on the Indus River. A comprehensive analysis, including an assessment of associated human health risks, was conducted. Thirty samples from all three sites for each fish species, with an average body weight of 160 ± 32 g, were collected from Chashma Barrage. Water quality parameters indicated suitability for fish growth and health. Heavy metal concentrations were determined using an atomic absorption spectrometer. Results indicated elevated levels of Cd, Cr, and Cu in sediment and Pb and Cd in water, surpassing WHO standard limits. Among the fish species, bottom feeder (C. mrigala) exhibited significantly (P < 0.05) higher heavy metal levels in its tissues (gills, liver, and muscle) compared to column feeder (L. rohita) and surface feeder (C. catla). Liver tissues across all species showed higher heavy metal bioaccumulation, followed by gills. Principal component analysis (PCA) revealed strong correlations among heavy metals in sediment, gills, muscle, and water in every fish species. However, the vector direction suggests that Cr was not correlated with other heavy metals in the system, indicating a different source. The human health risk analysis revealed lower EDI, THQ, and HI values (< 1) for the fish species, indicating no adverse health effects for the exposed population. The study emphasizes the bioaccumulation differences among fish species, underscoring the higher heavy metal concentrations in bottom feeder fish within Chashma Barrage.

In vivo and in silico studies of the effects of oil extracted from Cannabis sativa L. seeds on healing of burned skin wounds in rats.

Introduction: This study investigates the potential effects of cannabis seed oil (CSO) on the wound healing process. The aim was to assess the efficacy of CSO in treating skin wounds using an animal model and to explore its anti-inflammatory properties through in silico analysis. Methods: Eighteen male albino Wistar rats, weighing between 200 and 250 g, were divided into three groups: an untreated negative control group, a group treated with the reference drug silver sulfadiazine (SSD) (0.01 g/mL), and a group treated topically with CSO (0.962 g/mL). The initial wound diameter for all groups was 1 cm. In silico studies were conducted using Maestro 11.5 to evaluate the anti-inflammatory effects of phytoconstituents against cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Results: CSO and SSD treatments led to a significant reduction (p <0.05) in the size of burned skin wounds by day 5, with contraction rates of 53.95% and 45.94%, respectively, compared to the untreated negative control group. By day 15, wounds treated with CSO and SSD had nearly healed, showing contraction rates of 98.8% and 98.15%, respectively. By day 20, the wounds treated with CSO had fully healed (100%), while those treated with SSD had almost completely healed, with a contraction rate of 98.97%. Histological examination revealed granulated tissue, neo-blood vessels, fibroblasts, and collagen fibers in wounds treated with CSO. In silico studies identified arachidic acid, γ-linolenic acid, and linolenic acid as potent inhibitors of COX-1 and COX-2. Serum biochemical parameters indicated no significant changes (p > 0.05) in liver and kidney function in rats treated with CSO, whereas a significant increase (p < 0.01) in ALAT level was observed in rats treated with SSD. Discussion: The findings demonstrate that CSO has a promising effect on wound healing. The CSO treatment resulted in significant wound contraction and histological improvements, with no adverse effects on liver and kidney function.However, the study's limitations, including the small sample size and the need for detailed elucidation of CSO's mechanism of action, suggest that further research is necessary. Future studies should focus on exploring the molecular pathways and signaling processes involved in CSO's pharmacological effects.

Sclerotia degradation by Trichoderma-mycoparasitic; an effective and sustainable trend in the drop lettuce disease control caused by Sclerotinia sclerotiorum.

Controlling the hazard of sclerotia produced by the Sclerotinia sclerotiorum is very complex, and it is urgent to adopt an effective method that is harmonious environmentally to control the disease. Among the six isolates isolated from the rhizosphere of lettuce, the isolate HZA84 demonstrated a high activity in its antagonism towards Sclerotinia sclerotiorum in vitro, and produces siderophore. By amplification of internal transcribed spacer (ITS), translation elongation factor 1-alpha (TEF1-α), and RNA polymerase II subunit (RPB2) genes, the isolate HZA84 was identified as Trichoderma asperellum, which was confirmed by analysis of phylogenetic tree. The Scanning electron microscope monitoring detected that the isolate HZA84 spread over the sclerotial surface, thus, damaging, decomposing, and distorting the globular cells of the outer cortex of the sclerotia. The Real-time polymerase chain reaction (RT-qPCR) analysis disclosed the overexpression of two genes (chit33 and chit37) encoding the endochitinase in addition to one gene (prb1) encoding the proteinase during 4 and 8 days of the parasitism behavior of isolate HZA84 on the sclerotia surface. These enzymes aligned together in the sclerotia destruction by hyperparasitism. On the other hand, the pots trial revealed that spraying of isolate HZA84 reduced the drop disease symptoms of lettuce. The disease severity was decreased by 19.33 and the biocontrol efficiency was increased by 80.67% within the fourth week of inoculation. These findings magnify the unique role of Trichoderma in disrupting the development of plant diseases in sustainable ways.

Mitigation of cisplatin-induced hepatotoxicity by Salvia officinalis: Attenuation of oxidative damage and inflammation in rats.

Salvia officinalis L., commonly known as sage and belonging to the Lamiaceae family, is a medicinal herb indigenous to the Mediterranean region. It is celebrated for its diverse pharmacological properties and traditional uses in folk medicine, particularly in addressing hepatotoxicity. Cisplatin (Cis), a potent chemotherapeutic agent widely employed in cancer treatment, is recognized for its efficacy but often accompanied by adverse effects, including hepatotoxicity. The aim of this study was to assess whether an ethanolic S. officinalis extract (ESOE) could provide protection against Cis-induced hepatotoxicity in an experimental rat model. The ESOE was prepared using standard extraction techniques, and its chemical constituents were elucidated through UPLC-ESI-MS/MS analysis, revealing the presence of bioactive compounds such as alkaloids, phenolic compounds, and flavonoids, which are associated with various therapeutic effects, including hepatoprotection. Adult male albino rats were allocated into four groups: control, ESOE (250 mg/kg), Cis (7.5 mg/kg), and ESOE (250 mg/kg) + Cis (7.5 mg/kg). The treatment duration lasted 21 days, with Cis administration on the 22nd day. Twenty-four hours post-Cis administration, blood and liver samples were collected for analysis. Cis-induced hepatotoxicity was evidenced by alterations in hematological parameters, including erythrocyte, thrombocyte, leukocyte, and lymphocyte counts, alongside elevated serum levels of liver enzymes (ALT, LDH, AST, ALP, and GGT), indicative of liver damage. Furthermore, Cis exposure resulted in increased hepatic malondialdehyde (MDA) and Nitric oxide (NO) levels, oxidative stress markers, coupled with decreased levels of reduced glutathione (GSH), a non-enzymatic antioxidant, and histopathological changes in liver tissue, characterized by necrosis and inflammation. Additionally, Cis treatment led to elevated levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), TNF-α, and IL-6, indicating oxidative stress and inflammation. Remarkably, pretreatment with ESOE ameliorated these Cis-induced hepatotoxic effects, as evidenced by improved hematological parameters, reduced liver enzyme activities, alleviated oxidative stress, and ameliorated histopathological alterations. The observed hepatoprotective effects of ESOE against Cis-induced liver injury may be attributed to its antioxidant and anti-inflammatory properties, highlighting its potential as a natural therapeutic agent in mitigating chemotherapy-associated hepatotoxicity.

Analyzing the impact of pesticides on the indus river: contamination levels in water, sediment, fish, and associated human health risks.

Pesticides are frequently used to protect crop yields and manage malaria vectors; however, their inadvertent transport into aquatic habitats poses a significant concern. Various anthropogenic activities influence the Indus River in Pakistan. This study aimed to assess the presence of eight pesticide residues at three different sites (Kalabagh, Kundian, and Chashma) in water, sediment, and the fish species (Labeo rohita) during both dry and wet seasons to measure the intensity of this pressure. Pesticide analysis was carried out using gas chromatography equipped with an electron capture detector. The results revealed the highest concentrations of pesticides during both dry and wet seasons at all sites, measuring 0.83 and 0.62 µg/l (water), 12.37 and 9.20 µg/g/dw (sediment), and 14.27 and 11.29 µg/g/ww (L. rohita), respectively. Overall, pesticide concentrations were higher in the dry season than in the wet season across all study sites. Based on detection frequency and concentration in both seasons at all sites, dominant pesticides included cypermethrin and carbofuran (in water), as well as endosulfan and cypermethrin (in sediment and fish tissue). Levels of endosulfan and cypermethrin exceeded standard limits. Moreover, principal component analysis (PCA) indicated no correlation among pesticides in fish tissue, sediment, and water. However, pesticides exhibited different behavior in different seasons. Furthermore, endosulfan and triazophos impose great human health risk, as indicated by the THQ value (> 1). The overall HI value was greater for site 1 in the dry season (8.378). The study concluded that the presence of agricultural pesticides in the Indus River poses a risk to aquatic life and has the potential to disrupt the entire food chain. This highlights the importance of sustainable practices for the study area and Pakistan overall agricultural and environmental sustainability. It is further recommended to strengthen regulations for reduced pesticide use and promote eco-friendly pest management.

Implications of Heavy Metal Accumulation in Fish Feed, Water, Sediment, and Different Fish Species in a Polyculture System.

Heavy metal bioaccumulation in organisms is primarily a result of dietary uptake. The current study examines the concentrations of heavy metals (Pb, Cd, Cr, and Cu) in fish feed, water, sediment, and three fish species (Catla catla, Labeo rohita, and Cyprinus carpio) from different feeding zones in a polyculture pond system. Furthermore, associated human health risks were also evaluated. The fish samples (n = 25 for each species) were collected from 10 different fish ponds in the Kohat district, Pakistan. Heavy metals were determined using an atomic absorption spectrometer. Results revealed higher concentrations of heavy metals in sediment, followed by water. However, the concentration of heavy metals in fish feed was lower than the standard limits. In the case of fish, the bottom feeder (C. carpio) notably exhibited higher (P < 0.05) levels of heavy metals than the column feeder (L. rohita) and surface feeder (C. catla) fish. Moreover, in the liver of all fish species, the bioaccumulation of heavy metals was higher, followed by the gills. Principal component analysis (PCA) demonstrated a strong correlation of heavy metals in C. carpio gills, flesh, feed, and pond water, while the heavy metals in the liver correlated with the detected metals in sediment. The human health risk analysis shows that bottom feeder fish had higher estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI) values (> 1). Consequently, the exposed population may experience adverse health effects. The findings of this study suggest that the bottom feeder (C. carpio) bioaccumulates a higher concentration of heavy metals than column (L. rohita) and surface feeder (C. catla) in the polyculture system.

Suppression of Root Rot Fungal Diseases in Common Beans (Phaseolus vulgaris L.) through the Application of Biologically Synthesized Silver Nanoparticles.

The biosynthesis of silver nanoparticles (AgNPs) using plant extracts has become a safe replacement for conventional chemical synthesis methods to fight plant pathogens. In this study, the antifungal activity of biosynthesized AgNPs was evaluated both in vitro and under greenhouse conditions against root rot fungi of common beans (Phaseolus vulgaris L.), including Macrophomina phaseolina, Pythium graminicola, Rhizoctonia solani, and Sclerotium rolfsii. Among the eleven biosynthesized AgNPs, those synthesized using Alhagi graecorum plant extract displayed the highest efficacy in suppressing those fungi. The findings showed that using AgNPs made with A. graecorum at a concentration of 100 µg/mL greatly slowed down the growth of mycelium for R. solani, P. graminicola, S. rolfsii, and M. phaseolina by 92.60%, 94.44%, 75.93%, and 79.63%, respectively. Additionally, the minimum inhibitory concentration (75 µg/mL) of AgNPs synthesized by A. graecorum was very effective against all of these fungi, lowering the pre-emergence damping-off, post-emergence damping-off, and disease percent and severity in vitro and greenhouse conditions. Additionally, the treatment with AgNPs led to increased root length, shoot length, fresh weight, dry weight, and vigor index of bean seedlings compared to the control group. The synthesis of nanoparticles using A. graecorum was confirmed using various physicochemical techniques, including UV spectroscopy, Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) analysis. Collectively, the findings of this study highlight the potential of AgNPs as an effective and environmentally sustainable approach for controlling root rot fungi in beans.

The effect mechanism of ergosterol from the nutritional mushroom Leucocalocybe mongolica in breast cancer cells: Protein expression modulation and metabolomic profiling using UHPLC-ESI-Q.

The ergosterol from mushrooms has gained significant ethnopharmacological importance in various cultures, including China, Japan, and Europe. This compound has been found to possess immune-boosting and anti-inflammatory properties, making it useful in the treatment of immune disorders. In this study, we focused on investigating the potential anticancer properties of ergosterol isolated from the edible mushroom Leucocalocybe mongolica in breast cancer cell lines. The ergosterol was purified and identified using advanced analytical techniques such as ESI-MS and NMR. We conducted cell proliferation assays on 4 T1 breast cancer cells to assess the cytotoxic effects of ergosterol. Furthermore, we analyzed the transcription levels of BAX, caspase-7, BCL-2, STAT-3, and PARP proteins using real-time PCR and Western blot analysis. Additionally, we employed non-targeted ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UPLC-MS/MS) to study the potential mechanisms underlying the anticancer effects of ergosterol at the metabolomics level. The results demonstrated a significant reduction in cell viability and the induction of apoptosis upon treatment with ergosterol, especially at higher concentrations (P < 0.05). Moreover, ergosterol affected the expression of cancer-related genes, upregulating pro-apoptotic proteins such as BAX, caspase-7, and PARP, while downregulating the anti-apoptotic proteins BCL-2 and STAT-3 (P < 0.05). Western blot analysis confirmed these findings and provided further evidence of ergosterol's role in inducing apoptosis. Metabolomics analysis revealed substantial changes in pathways related to amino acid, antioxidant, and carbohydrate metabolism. In conclusion, our study demonstrates that ergosterol exhibits anticancer effects by inducing apoptosis and modulating metabolic pathways in breast cancer cells.

Nickel oxide nanoparticles: A new generation nanoparticles to combat bacteria Xanthomonas oryzae pv. oryzae and enhance rice plant growth.

Recently, nanotechnology is among the most promising technologies used in all areas of research. The production of metal nanoparticles using plant parts has received significant attention for its environmental friendliness and effectiveness. Therefore, we investigated the possible applications of biological synthesized nickel oxide nanoparticles (NiONPs). In this study, NiONPs were synthesized through biological method using an aqueous extract of saffron stigmas (Crocus sativus L). The structure, morphology, purity, and physicochemical properties of the obtained NPs were confirmed through Scanning/Transmission Electron Microscopy attached with Energy Dispersive Spectrum, X-ray Diffraction, and Fourier transform infrared. The spherically shaped NiONPs were found by Debye Scherer's formula to have a mean dimension of 41.19 nm. The application of NiONPs in vitro at 50, 100, and 200 µg/mL, respectively, produced a clear region of 2.0, 2.2, and 2.5 cm. Treatment of Xoo cell with NiONPs reduced the growth and biofilm formation, respectively, by 88.68% and 83.69% at 200 µg/mL. Adding 200 µg/mL NiONPs into Xoo cells produced a significant amount of ROS in comparison with the control. Bacterial apoptosis increased dramatically from 1.05% (control) to 99.80% (200 µg/mL NiONPs). When compared to the control, rice plants treated with 200 µg/mL NiONPs significantly improved growth characteristics and biomass. Interestingly, the proportion of diseased leaf area in infected plants with Xoo treated with NiONPs reduced to 22% from 74% in diseased plants. Taken together, NiONPs demonstrates its effectiveness as a promising tool as a nano-bactericide in managing bacterial infection caused by Xoo.

Impacts of Biosynthesized Manganese Dioxide Nanoparticles on Antioxidant Capacity, Hematological Parameters, and Antioxidant Protein Docking in Broilers.

Using green tomato extract, a green approach was used to synthesize manganese oxide nanoparticles (MnO2NPs). The synthesis of MnO2NPs was (20.93-36.85 nm) confirmed by energy-dispersive X-ray (EDX), scanning and transmission electron microscopy (SEM and TEM), Fourier transform infrared spectroscopy (FTIR), and UV-visible spectroscopy (UV-vis) analyses. One hundred fifty-day-old Arbor Acres broiler chicks were randomly divided into five groups. The control group received a diet containing 60 mg Mn/kg (100% NRC broiler recommendation). The other four groups received different levels of Mn from both bulk MnO2 and green synthesized MnO2NPs, ranging from 66 to 72 mg/kg (110% and 120% of the standard level). Each group comprised 30 birds, in three replicates of 10 birds each. Generally, the study's results indicate that incorporating MnO2NPs as a feed additive had no negative effects on broiler chick growth, antioxidant status, and overall physiological responses. The addition of MnO2NPs, whether at 66 or 72 mg/kg, led to enhanced superoxide dismutase (SOD) activity in both serum and liver tissues of the broiler chicks. Notably, the 72 mg MnO2NPs group displayed significantly higher SOD activity compared to the other groups. The study was further justified through docking. High throughput targeted docking was performed for proteins GHS, GST, and SOD with MnO2. SOD showed an effective binding affinity of -2.3 kcal/mol. This research sheds light on the potential of MnO2NPs as a safe and effective feed additive for broiler chicks. Further studies are required to explore the underlying mechanisms and long-term effects of incorporating MnO2NPs into broiler feed, to optimize broiler production and promote its welfare.

Sublethal Concentrations of Cadmium and Lead: Effects on Hemato-Biochemical Parameters and Tissue Accumulation in Wallagu attu.

The exposure of fish to heavy metals can significantly impact physiological processes and potentially lead to adverse health effects. This study assesses the effects of exposure to Cd and Pb sublethal concentrations in water on Wallagu attu. A total of 48 fish with an average body weight of 145.5 ± 26 g were distributed among three groups (control, Cd-treated, and Pb-treated) within 60 L fiberglass tanks. They were exposed to 30% sublethal concentrations of Cd and Pb for durations of 1, 15, and 30 days. Following this exposure, an assessment was conducted on metal bioaccumulation and hemato-biochemical responses. Results revealed a significantly (P < 0.05) higher concentration of heavy metals in the fish tissues of metals exposed groups than in the control. The concentration of Cd and Pb increases in fish tissues (kidney > gills > intestine) with exposure time. In most cases, the Pb-exposed group exhibited significantly (P < 0.05) higher concentrations of Pb in different tissues than the Cd-treated group. With extended exposure time, the activities of CAT and SOD show a significant decrease in both Cd and Pb-treated groups. However, the reduction in activities was more pronounced in the Cd-exposed group. On 15 and 30 days, the levels of red blood cells (RBC), hemoglobin (HB), hematocrit (HCT), and total protein (TP) decrease in groups exposed to Cd and Pb. The cortisol and glucose levels exhibit a more noticeable (P < 0.05) increase with prolonged exposure to Cd and Pb than the control group. On day 30, the survival rate decreased more in the Pb-exposed group. The findings of this study indicate that exposure to sublethal doses of Cd and Pb induces stress in Wallagu attu, resulting in rapid changes in specific hemato-biochemical parameters.

Quercetin modulates expression of serum exosomal long noncoding RNA NEAT1 to regulate the miR-129-5p/BDNF axis and attenuate cognitive impairment in diabetic mice.

AIMS: Cognitive impairment poses a considerable health challenge in the context of type 2 diabetes mellitus (T2DM), emphasizing the need for effective interventions. This study delves into the therapeutic efficacy of quercetin, a natural flavonoid, in mitigating cognitive impairment induced by T2DM in murine models. MATERIALS AND METHODS: Serum exosome samples were obtained from both T2DM-related and healthy mice for transcriptome sequencing, enabling the identification of differentially expressed mRNAs and long noncoding RNAs (lncRNAs). Subsequent experiments were conducted to ascertain the binding affinity between mmu-miR-129-5p, NEAT1 and BDNF. The structural characteristics and dimensions of isolated exosomes were scrutinized, and the expression levels of exosome-associated proteins were quantified. Primary mouse hippocampal neurons were cultured for in vitro validation, assessing the expression of pertinent genes as well as neuronal vitality, proliferation, and apoptosis capabilities. For in vivo validation, a T2DM mouse model was established, and quercetin treatment was administered. Changes in various parameters, cognitive ability, and the expression of insulin-related proteins, along with pivotal signaling pathways, were monitored. KEY FINDINGS: Analysis of serum exosomes from T2DM mice revealed dysregulation of NEAT1, mmu-miR-129-5p, and BDNF. In vitro investigations demonstrated that NEAT1 upregulated BDNF expression by inhibiting mmu-miR-129-5p. Overexpression of mmu-miR-129-5p or silencing NEAT1 resulted in the downregulation of insulin-related protein expression, enhanced apoptosis, and suppressed neuronal proliferation. In vivo studies validated that quercetin treatment significantly ameliorated T2DM-related cognitive impairment in mice. SIGNIFICANCE: These findings suggest that quercetin holds promise in inhibiting hippocampal neuron apoptosis and improving T2DM-related cognitive impairment by modulating the NEAT1/miR-129-5p/BDNF pathway within serum exosomes.

Fumaria indica (Hausskn.) Pugsley Hydromethanolic Extract: Bioactive Compounds Identification, Hypotensive Mechanism, and Cardioprotective Potential Exploration.

Fumaria indica (Hausskn.) Pugsley (FIP), a member of the Papaveraceae family, has a documented history of use in traditional medicine to treat cardiovascular ailments, particularly hypertension, and has shown substantial therapeutic efficacy among native cultures worldwide. However, the identification of bioactive compounds and the mechanism of hypotensive effect with the cardioprotective potential investigations are yet to be determined. The study aimed to identify bioactive compounds, explore the hypotensive mechanism and cardioprotective potential, and assess the safety of Fumaria indica (Hausskn.) Pugsley hydromethanolic extract (Fip.Cr). LC ESI-MS/MS analysis was performed to identify the bioactive compounds. In vitro experiments were conducted on isolated rat aorta and atria, and an in vivo invasive BP measurement model was used. Acute and subacute toxicities were assessed for 14 and 28 days, respectively. Isoproterenol (ISO) was used to develop the rats' myocardial infarction damage model. The mRNA levels of NLRP3 inflammasome and the abundance level of Firmicutes and Lactobacillus were measured by qRT-PCR. The hypotensive effect of FIP bioactive compounds was also investigated using in silico methods. Fip. Cr LC ESI-MS/MS analysis discovered 33 bioactive compounds, including alkaloids and flavonoids. In isolated rat aorta, Fip.Cr reversed contractions induced by K+ (80 mM), demonstrating a calcium entry-blocking function, and had a vasorelaxant impact on phenylephrine (PE) (1 µM)-induced contractions unaffected by L-NAME, ruling out endothelial NO participation. Fip.Cr caused negative chronotropic and inotropic effects in isolated rat atria unaffected by atropine pretreatment, eliminating cardiac muscarinic receptor involvement. Safety evaluation showed no major adverse effects. In vivo, invasive BP measurement demonstrated a hypotensive effect comparable to verapamil. Fip.Cr protected the rats from ISO-induced MI interventions significantly in biometrical and cardiac serum biochemical indicators and histological examinations by reducing inflammation via inhibiting NLRP3 inflammasome and elevating Firmicutes and Lactobacillus levels. The network pharmacology study revealed that the FIP hypotensive mechanism might involve MMP9, JAK2, HMOX1, NOS2, NOS3, TEK, SERPINE1, CCL2, and VEGFA. The molecular docking study revealed that FIP bioactive compounds docked better with CAC1C_ HUMAN than verapamil. These findings demonstrated that Fip.Cr's hypotensive mechanism may include calcium channel blocker activity. Fip.Cr ameliorated ISO-induced myocardial infarction in rats by attenuating inflammation, which might be via inhibiting NLRP3 inflammasome and may prove beneficial for treating MI.

Phytosynthesized Iron Oxide Nanoparticles Using Aqueous Extract of Saccharum arundinaceum (Hardy Sugar Cane), Their Characterizations, Antiglycation, and Cytotoxic Activities.

The goal of the current study is to achieve plant-mediated synthesis of iron oxide nanoparticles (Fe2O3 NPs). The plant extract of Saccharum arundinaceum was used as a reducing and stabilizing agent for the synthesis of Fe2O3 NPs. Different techniques such as energy-dispersive X-ray analysis (EDX), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy (UV-vis) were used to characterize the synthesis of Fe2O3 NPs. UV-visible spectroscopy verified the synthesis of Fe2O3 NPs using a surface plasmon resonance peak at a wavelength of 370 nm. SEM analysis specifies the spherical morphology of the synthesized nanoparticles with a size range between 30 and 70 nm. The reducing and capping materials of Fe2O3 NPs were revealed by FT-IR analysis based on functional group identification. The plant extract contained essential functional groups, such as C-H, C-O, N-H, -CH2, and -OH, that facilitate the green synthesis of Fe2O3 NPs. The EDX analysis detected the atomic percentage with the elemental composition of Fe2O3 NPs, while the XRD pattern demonstrated the crystallinity of Fe2O3 NPs. Furthermore, the synthesized Fe2O3 NPs showed potential antiglycation activity under in vitro conditions, which was confirmed by the efficient zone of inhibition on glycation of bovine serum albumin/glucose (BSA-glucose) in the order <100 < 500 < 1000 µg/mL, which revealed that Fe2O3 NPs showed significant antiglycation activity. Additionally, the cytotoxic activity against brain glioblastoma cells was assessed using the MTT assay, which exhibited diminished cytotoxic activity at concentrations lower than 300 µg/mL. Thus, we assumed that the resulting Fe2O3 NPs are a good option for use in drug delivery and cancer treatments.

Mechanistic inhibition of gastric cancer-associated bacteria Helicobacter pylori by selected phytocompounds: A new cutting-edge computational approach.

Background: Helicobacter pylori (H. pylori) is a persistent bacterial inhabitant in the stomachs of approximately half the global populace. This bacterium is directly linked to chronic gastritis, leading to a heightened risk of duodenal and gastric ulcer diseases, and is the predominant risk factor for gastric cancer - the second most common cause of cancer-related deaths globally. The increasing prevalence of antibiotic resistance necessitates the exploration of innovative treatment alternatives to mitigate the H. pylori menace. Methods: Initiating our study, we curated a list of thirty phytochemicals based on previous literature and subjected them to molecular docking studies. Subsequently, eight phytocompounds-Glabridin, Isoliquiritin, Sanguinarine, Liquiritin, Glycyrrhetic acid, Beta-carotin, Diosgenin, and Sarsasapogenin-were meticulously chosen based on superior binding scores. These were further subjected to an extensive computational analysis encompassing ADMET profiling, drug-likeness evaluation, principal component analysis (PCA), and molecular dynamic simulations (MDs) in comparison with the conventional drug, Mitomycin. Results: The natural compounds investigated demonstrated superior docking affinities to H. pylori targets compared to the standard Mitomycin. Notably, the phytocompounds Diosgenin and Sarsasapogenin stood out due to their exceptional binding affinities and pharmacokinetic properties, including favorable ADMET profiles. Conclusion: Our comprehensive and technologically-advanced approach showcases the potential of identified phytocompounds as pioneering therapeutic agents against H. pylori-induced gastric malignancies. In light of our promising in silico results, we recommend these natural compounds as potential candidates for advancing H. pylori-targeted drug development. Given their potential, we strongly advocate for subsequent in vitro and in vivo studies to validate their therapeutic efficacy against this formidable gastrointestinal bacterium.

Survivin-targeted nanomedicine for increased potency of abiraterone and enzalutamide against prostate cancer.

Prostate cancer is the leading and most aggressive cancer around the world, several therapeutic approaches have emerged but none have achieved the satisfactory result. However, these therapeutic approaches face many challenges related to their delivery to target cells, including their in vivo decay, the limited uptake by target cells, the requirements for nuclear penetration (in some cases), and the damage caused to healthy cells. These barriers can be avoided by effective, targeted, combinatorial approaches, with minimal side effects, which are being investigated for the treatment of cancer. Here, we developed a combinatorial nanomedicine comprising abiraterone and enzalutamide bioconjugated survivin-encapsulated gold nanoparticles (AbEzSvGNPs) for targeted therapy of prostate cancer. AbEzSvGNPs were characterized by different biophysical techniques such as UV visible spectroscopy, dynamic light scattering, zeta potential, transmission electron microscope, and Fourier transform infrared spectroscopy. Interestingly, the effect of abiraterone, enzalutamide and surviving encapsulated gold nanoparticles was found to be synergistic in nature in AbEzSvGNPs against DU 145 (IC50 = 4.21 µM) and PC-3 (IC50 = 5.58 µM) cells and their potential was observed to be greatly enhanced as compared with the combined effect of the drugs (abiraterone and enzalutamide) in their free form. Furthermore, AbEzSvGNPs were found to be highly safe and did not exhibit significant cytotoxicity against normal rat kidney cells. The observed effects of AbEzSvGNPs involved the modulation of different signaling pathways in prostate cancer cells. This delivery system employed non-androgen receptor-dependent delivery of abiraterone and enzalutamide. The anionic AbEzSvGNPs delivered abiraterone and enzalutamide unaltered into the nucleus through caveolae mediated internalization to act nonspecifically on DNA; internalization of the anionic nanoparticles into the cytoplasm was also observed via other routes. AbEzSvGNPs synthesized and evaluated in this study are promising candidates for prostate cancer therapy.

IgG antibodies mediated gold nanoparticles conjugated to methotrexate as targeted chemotherapy for lung cancer.

Vincamine, a natural chemical, was used as a reducing agent in the synthesis of IgG antibodies mediated biogenic gold nanoparticles (IgGAuNPs). Eventually, the synthesised IgGAuNPs were bioconjugated with the chemotherapeutic drug methotrexate (MTX-IgGAuNPs). The IgG isotype can target cancer cells through polymorphic Fc gamma receptors (FcγRs) and have therapeutic effects. They can restrict cell division by inhibiting different intracellular signal transduction pathways and activating NK cells and macrophages through antibody-dependent cellular cytotoxicity and macrophage-mediated antibody-dependent phagocytosis, respectively. Further, IgGAuNPs and MTX-IgGAuNPs were characterised by physical techniques. Moreover, 3D conformational changes in the structure of IgG were analysed by fluorescence spectroscopy during and after the synthesis of IgGAuNPs. Furthermore, the IgGAuNPs and MTX-IgGAuNPs were effective against lung cancer (A549 cells), while they were found to be non-toxic against normal cells (NRK cells). The effectiveness of IgGAuNPs and MTX-IgGAuNPs was examined by MTT cytotoxicity assay, DCFDA method for the production of ROS, and release of Cyt-c from the mitochondria for caspase-3-mediated apoptosis. Moreover, the confirmation of internalisation of particles into the nucleus was examined under the DAPI assay, and it was found that particles caused nuclear fragmentation, which was also an indication of apoptosis.