Biochemical Alterations Research Articles

Intranasal Insulin Eases Autism in Rats via GDF-15 and Anti-Inflammatory Pathways.

In rat models, it is well-documented that chronic administration of propionic acid (PPA) leads to autism-like behaviors. Although the intranasal (IN) insulin approach is predominantly recognized for its effects on food restriction, it has also been shown to enhance cognitive memory by influencing various proteins, modulating anti-inflammatory pathways in the brain, and reducing signaling molecules such as interleukins. This study seeks to explore the potential therapeutic benefits of IN insulin in a rat model of autism induced by PPA. Thirty male Wistar albino rats were categorized into three cohorts: the control group, the PPA-induced autism (250 mg/kg/day intraperitoneal PPA dosage for five days) group, treated with saline via IN, and the PPA-induced autism group, treated with 25 U/kg/day (250 µL/kg/day) insulin via IN. All treatments were administered for 15 days. After behavioral testing, all animals were euthanized, and brain tissue and blood samples were collected for histopathological and biochemical assessments. Following insulin administration, a substantial reduction in autism symptoms was observed in all three social behavior tests conducted on the rats. Moreover, insulin exhibited noteworthy capabilities in decreasing brain MDA, IL-2, IL-17, and TNF-α levels within autism models. Additionally, there is a notable elevation in the brain nerve growth factor level (p < 0.05) and GDF-15 (p < 0.05). The assessment of cell counts within the hippocampal region and cerebellum revealed that insulin displayed effects in decreasing glial cells and inducing a significant augmentation in cell types such as the Purkinje and Pyramidal cells. The administration of insulin via IN exhibits alleviating effects on autism-like behavioral, biochemical, and histopathological alterations induced by PPA in rats. Insulin-dependent protective effects show anti-inflammatory, anti-oxidative, and neuroprotective roles of insulin admitted nasally.

Evaluation of Anti-Depressant Potential of Standardized Hydroethanolic Extract of S. barbata D. Don Using Chronic Unpredictable Mild Stress Model

Background: S. barbata D. Don is a Chinese herb, that belongs to the family Lami-aceae. It has established traditional use in ethnomedicine for treating various ailments, includ-ing mood disorders and sleep disorders, which led to growing interest in exploring its neuro-logical potential, particularly as a potential anti-depressant agent. Aims: This study explores the anti-depressant potential of the HSBE utilizing a Chronic Un-predictable Mild Stress-induced depression model in mice. Additionally, the research aims to elucidate the underlying mechanisms of action. Methods: Swiss albino mice were subjected to a 3-week CUMS paradigm and subsequently administered HSBE at doses of 200 and 400 mg/kg via oral administration. The behavioral alterations were evaluated using the FST, TST, OFT, and SPT. Brain levels of serotonin, dopa-mine, and nor-epinephrine were estimated in different brain regions (cortex, hippocampus, and hypothalamus) to uncover the molecular mechanism. Additionally, assays for monoamine oxi-dase-A, monoamine oxidase-B, and antioxidant enzyme activities were conducted. Plasma ni-trite and corticosterone levels were also measured to get further insight into potential mecha-nisms underlying the anti-depressant effects of HSBE. Results: HSBE significantly ameliorated depressive-like behavior induced by CUMS para-digm, as evidenced by reduced immobility in FST and TST, increased locomotor activity in OFT, and improved sucrose preference in SPT. Neurochemical analysis revealed a significant increase in serotonin, dopamine, and norepinephrine levels in the cortex, hippocampus, and hypothalamus of HSBE-treated mice, implying a potential regulation of monoaminergic neuro-transmitter levels. Moreover, biochemical analyses demonstrated a significant inhibition of both MAO-A and MAO-B activity, contributing to the increase of the brain levels of neuro-transmitters. The administration of HSBE also led to a significant enhancement of antioxidant enzyme activities and reduced brain lipid peroxidation, indicating a pronounced antioxidant effect of HSBE. Furthermore, decreased plasma nitrite and corticosterone levels provided ad-ditional insights into HSBE's potential multi-targeted anti-depressant mechanism. Conclusion: This study indicates that HSBE exhibits robust anti-depressant properties, sup-ported by behavioral, neurochemical, and biochemical alterations. These findings underscore the therapeutic promise of HSBE as a natural intervention for depressive disorders, warranting further clinical exploration.

Lambda Cyhalothrin (LCT)-Induced Long-term Pesticide Effects of Albino Rats

Lambda cyhalothrin (LCT), a prominent pyrethroid insecticide, has been linked to a number of negative side effects in non-target animals, including mammals. This study investigated the long-term consequences of lambda- cyhalothrin (LCT) exposure on albino rats, including physiological, biochemical, and behavioural alterations. Adult albino rats were given sub-lethal lambda-cyhalothrin (LCT) doses over an extended period to simulate chronic exposure. Body weight, organ histology, serum biochemical markers, and behavioural reactions were all examined to determine the toxicological impact. The biochemical markers of liver and kidney function showed substantial variation, indicating organ damage. Histopathological evaluation of the liver and kidney tissues revealed structural damage consistent with the biochemical abnormalities discovered. The neurotoxic potential of lambda-cyhalothrin (LCT) was further demonstrated by the exposed rats' notable behavioural changes, which included decreased locomotor activity and increased anxiety-like behaviour. These findings emphasise the potential long-term risks associated with repeated exposure to lambda cyhalothrin (LCT), emphasizing the need for additional research and strong regulations to understand the implications for environmental safety and public health.

Tadalafil pretreatment attenuates doxorubicin-induced hepatorenal toxicity by modulating oxidative stress and inflammation in Wistar rats

Doxorubicin (DOX) is a widely used anticancer agent, but its clinical application is limited by significant off-target hepatorenal toxicity. Tadalafil (TAD), a selective phosphodiesterase-5 inhibitor used mainly for erectile dysfunction and pulmonary arterial hypertension, has shown potential in reducing oxidative stress. This study investigated TAD's chemoprotective effects and underlying mechanisms in DOX-induced hepatorenal toxicity in rats over 12 days. Eight groups of six rats each were orally pretreated with sterile water, silymarin (SIL), or TAD one hour before receiving intraperitoneal injections of 2.5 mg/kg DOX. On the 13th day, the rats were humanely sacrificed under inhaled halothane anesthesia, and serum was collected for hepatic and renal function tests, while liver and kidney tissues were analyzed for antioxidant enzyme activity, pro-inflammatory cytokines assay, and histopathological evaluation. DOX successfully induced hepatorenal toxicity, evidenced by significant increases (p<0.001, p<0.0001) in serum K+, urea, and creatinine levels, along with decreases in HCO3-, TCa2+, and Cl-. Tissue analysis showed reduced SOD, CAT, GST, and GPx activities, with elevated MDA and GSH levels. TAD pretreatment significantly ameliorated these biochemical alterations (p<0.05, p<0.001, p<0.0001), suggesting its potential as an effective chemoprophylactic adjuvant in the development of DOX-induced hepatorenal toxicity.

1D and 2D Feature Extraction Based on AAC and DC Protein Descriptors for Classification of Acetylation in Lysine Proteins using Convolutional Neural Network

Post-Translational Modification (PTM) denotes a biochemical alteration observed in an amino acid, playing crucial roles in protein activity, functionality, and the regulation of protein structure. The recognition of associated PTMs serves as a fundamental basis for understanding biological processes, therapeutic interventions for diseases, and the development of pharmaceutical agents. Using computational approaches (in silico) offers an efficient and cost-effective means to identify PTM sites swiftly. The exploration of protein classification commences with extracting protein sequence features that are subsequently transformed into numerical features for utilization in classification algorithms. Feature extraction methodologies involve using protein descriptors like Amino Acid Composition (AAC) and Dipeptide Composition (DC). Yet, these approaches exhibit a limitation by neglecting crucial amino acid sequence details. Moreover, both descriptor techniques generate a limited number of 1-dimensional (1D) features, which may not be ideal for processing through the Convolutional Neural Network (CNN) classification method. This investigation presents a novel approach to enhance feature diversity through protein sequence segmentation techniques, employing adjacent and overlapping segment strategies. Furthermore, the study illustrates the organization of features into 1D and 2D formats to facilitate processing through 1D CNN and 2D CNN classification methodologies. The findings of this research endeavour highlight the potential for enhancing the accuracy of acetylation classification in lysine proteins through the multiplication of protein sequence segments in a 2D configuration. The highest accuracy achieved for AAC and DC-based feature extraction methods is 77.39% and 76.75%, respectively.

Improving grapevine (Vitis vinifera L., cv. Superior Seedless) drought tolerance with cerium oxide nanoparticles: Agronomic and molecular insights

Drought stress poses a significant threat to global food security, impacting grapevine growth and development through physiological, biochemical, and molecular alterations. Cerium oxide nanoparticles (CeO2 NPs) have recently gained attention as a potential solution to environmental challenges, yet their application in grapevines remains understudied. This study examined the interaction between foliar-applied CeO2 NPs (at concentrations of 0, 5, 50, and 500 mg L−1) and drought stress (at 30% and 70% of field capacity humidity) in grapevine saplings. Among the different concentrations tested, 50 mg L−1 CeO2 NPs significantly improved the agronomic traits (e.g., shoot length, leaf area, shoot and root dry weights), photosynthetic parameters (stomatal conductance, chlorophyll a and chlorophyll b) and RWC of the grapevine saplings under drought stress. In parallel, CeO2 NPs significantly induced the activity of compatible solutes and SOD, CAT and APX under drought stress conditions. Moreover, the availability of CeO2 NPs alleviated drought stress-induced damage in grapevine saplings, as evidenced by decreased H2O2 (32.63%), EL (40.35%) and MDA (50.63%) levels. The molecular results revealed that CeO2 NPs caused significant changes in gene expression under drought stress by reducing the expression of the VvCLH1, VvCu/ZnSOD, VvRD29A and VvRBOHA genes by 4.54-fold, 27.73-fold, 14.6-fold and 46.12-fold, respectively. These findings suggest that CeO2 NPs applied via leaves enhance grapevine sapling resistance to drought-induced oxidative stress through cooperative enzymatic and nonenzymatic antioxidant mechanisms, influencing gene regulation. As a result, these findings revealed that CeO2 NPs could be promising elicitor candidates for alleviating drought stress in grapevines.

Protein corona alleviates adverse biological effects of nanoplastics in breast cancer cells.

Pollution from micro- and nanoplastics (MNPs) has long been a topic of concern due to its potential impact on human health. MNPs can circulate through human blood and, thus far, have been found in the lungs, spleen, stomach, liver, kidneys and even in the brain, placenta, and breast milk. While data are already available on the adverse biological effects of pristine MNPs (e.g. oxidative stress, inflammation, cytotoxicity, and even cancer induction), no report thus far clarified whether the same effects are modulated by the formation of a protein corona around MNPs. To this end, here we use pristine and human-plasma pre-coated polystyrene (PS) nanoparticles (NPs) and investigate them in cultured breast cancer cells both in terms of internalization and cell biochemical response to the exposure. It is found that pristine NPs tend to stick to the cell membrane and inhibit HER-2-driven signaling pathways, including phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways, which are associated with cancer cell survival and growth. By contrast, the formation of a protein corona around the same NPs can promote their uptake by endocytic vesicles and final sequestration within lysosomes. Of note is that such intracellular fate of PS-NPs is associated with mitigation of the biochemical alterations of the phosphorylated AKT (pAKT)/AKT and phosphorylated ERK (pERK)/ERK levels. These findings provide the distribution of NPs in human breast cancer cells, may broaden our understanding of the interactions between NPs and breast cancer cells and underscore the crucial role of the protein corona in modulating the impact of MNPs on human health.

Integrated Biomarker Response Emphasizing Neuronal Oxidative Stress and Genotoxicity Induced by Oxamyl in Sprague Dawley Rats: Ameliorative Effect of Ginseng as a Neuroprotective Agent.

Climate change has led to increased and varying pest infestation patterns, triggering a rise in pesticide usage and exposure. The effects of oxamyl, a widely used nematicide in Egypt, encompasses typical signs of carbamate intoxication; nevertheless, long-term effects of oxamyl exposure, particularly on the nervous system, require further elucidation. This study systematically investigated the mechanism and manifestations of repeated subacute exposure to sublethal doses of oxamyl in male SD rats. Data showed a dose-dependent genotoxic effect, manifested as increased bone marrow micronuclei and decreased brain expression of key genes involved in neurogenesis and neuronal development. Coincidently, brain histopathology showed dose-dependent neurodegeneration in various regions, associated with a significant increase in GFAP immunoreactivity, indicative of neuroinflammation. Biochemical examination revealed a typical pattern of cholinesterase inhibition by carbamates in serum and brain tissue, as well as increased oxidative stress markers in the brain such as SOD activity reduction, alongside an increase in NO and MDA. The ability of Ginseng at a 100 mg/Kg dose to ameliorate the effects of oxamyl exposure was investigated. Ginseng use, either as a protective or therapeutic regimen, attenuated the observed genotoxic, neuroinflammatory, and biochemical alterations. Our results indicate that repeated exposure to oxamyl triggers an integrative neurotoxic response, driven by genotoxicity, oxidative stress, and neuroinflammation, that could trigger an increase in neurological and cognitive disorders. These findings emphasize the urgent need for confirmatory translational studies in human subjects to assess these changes and inform policy decisions regarding safe levels of usage and appropriate agricultural and public health practices.

Pseudochrobactrum asaccharolyticum mitigates arsenic induced oxidative stress of maize plant by enhancing water status and antioxidant defense system

BackgroundOxidative stress mediated by reactive oxygen species (ROS) is a common denominator in arsenic toxicity. Arsenic stress in soil affects the water absorption, decrease stomatal conductance, reduction in osmotic, and leaf water potential, which restrict water uptake and osmotic stress in plants. Arsenic-induced osmotic stress triggers the overproduction of ROS, which causes a number of germination, physiological, biochemical, and antioxidant alterations. Antioxidants with potential to reduce ROS levels ameliorate the arsenic-induced lesions. Plant growth promoting rhizobacteria (PGPR) increase the total soluble sugars and proline, which scavenging OH radicals thereby prevent the oxidative damages cause by ROS. The main objective of this study was to evaluate the potential role of Arsenic resistant PGPR in growth of maize by mitigating arsenic stress.MethodologyArsenic tolerant PGPR strain MD3 (Pseudochrobactrum asaccharolyticum) was used to dismiss the ‘As’ induced oxidative stress in maize grown at concentrations of 50 and 100 mg/kg. Previously isolated arsenic tolerant bacterial strain MD3 “Pseudochrobactrum asaccharolyticum was used for this experiment. Further, growth promoting potential of MD3 was done by germination and physio-biochemical analysis of maize seeds. Experimental units were arranged in Completely Randomized Design (CRD). A total of 6 sets of treatments viz., control, arsenic treated (50 & 100 mg/kg), bacterial inoculated (MD3), and arsenic stress plus bacterial inoculated with three replicates were used for Petri plates and pot experiments. After treating with this MD3 strain, seeds of corn were grown in pots filled with or without 50 mg/kg and 100 mg/kg sodium arsenate.ResultsThe plants under arsenic stress (100 mg/kg) decreased the osmotic potential (0.8 MPa) as compared to control indicated the osmotic stress, which caused the reduction in growth, physiological parameters, proline accumulation, alteration in antioxidant enzymes (Superoxide dismutase-SOD, catalase-CAT, peroxidase-POD), increased MDA content, and H2O2 in maize plants. As-tolerant Pseudochrobactrum asaccharolyticum improved the plant growth by reducing the oxidation stress and antioxidant enzymes by proline accumulation. PCA analysis revealed that all six treatments scattered differently across the PC1 and PC2, having 85.51% and 9.72% data variance, respectively. This indicating the efficiency of As-tolerant strains. The heatmap supported the As-tolerant strains were positively correlated with growth parameters and physiological activities of the maize plants.ConclusionThis study concluded that Pseudochrobactrum asaccharolyticum reduced the ‘As’ toxicity in maize plant through the augmentation of the antioxidant defense system. Thus, MD3 (Pseudochrobactrum asaccharolyticum) strain can be considered as bio-fertilizer.

Zingiber officinale Ameliorates Acute Toxoplasmosis-Induced Pathology in Mice.

Toxoplasma gondii (T. gondii) infects one third of the world's population with significant illness, mainly among immunocompromised individuals and pregnant women. Treatment options for toxoplasmosis are limited which signifies the need for novel, potent, and safe therapeutic options. The goal of this study was to assess the effectiveness of the ethanolic extract of Zingiber officinale (Z. officinale) in treating mice infected with the RH T. gondii strain. Gas Chromatography/Mass Spectrometry (GC/MS) was used to identify components of ethanolic extract of Z. officinale. A total of 80 mice were randomly allocated into four experimental groups that contained 20 mice each. The first group was left uninfected (uninfected control), while three groups were infected with T. gondii RH virulent strain tachyzoites at 2500 tachyzoites/mouse. One infected group was left untreated (infected, untreated), whereas the other two groups were treated orally with either spiramycin (positive control) or Z. officinale ethanolic extract at doses of 200mg/kg and 500mg/kg, respectively for 5 days, starting the day of infection. Ten mice from each group were used to assess mice survival in different groups, whereas the other ten mice in each group were sacrificed on the 5th day post-infectin (dpi) to estimate the treatment efficacy by quantifying liver parasite load, liver function, nitric oxide (NO) production, and levels of antioxidant enzymes. Additionally, histopathological studies were performed to evaluate the therapeutic effect of Z. officinale treatment on toxoplasmosis-induced pathological alterations in liver, brain, and spleen. Treatment with Z. officinale ethanolic extract extended the survival of mice till 9th dpi compared to 7th dpi in infected untreated mice. Higher percentage of mice survived in Z. officinale-treated group compared to spiramycin-treatment group at different time points. Liver parasite loads were significantly lower in Z. officinale extract-treated mice and spiramycin-treated mice compared to infected untreated mice which correlated with significantly lower levels of serum liver enzymes (ALT, AST) and nitric oxide (NO), as well as significantly higher catalase (CAT) antioxidant enzyme activity. Scanning electron microscopy (SEM) examination of tachyzoites from the peritoneal fluid revealed marked damage in tachyzoites from Z. officinale-treated group compared to that from infected untreated mice. Moreover, treatment with Z. officinale ethanolic extract alleviated infection-induced pathological alterations and restored normal tissue morphology of liver, brain, and spleen. Our results demonstrated that Z. officinale treatment reduced parasite burden and reversed histopathological and biochemical alterations in acute murine toxoplasmosis. These findings support the potential utility of Z. officinale as a future effective natural therapeutic for toxoplasmosis. Further studies are needed to determine the effective active ingredient in Z. officinale extract that can be further optimized for treatment of toxoplasmosis.

Molecular fingerprint by omics-based approaches in saliva from patients affected by SARS-CoV-2 infection.

Clinical expression of coronavirus disease 2019 (COVID-19) infectionis widely variable including fatal cases and patients with mild symptoms and a rapid resolution. We studied saliva from 63 hospitalized COVID-19 patients and from 30 healthy controls by integrating large-scale proteomics, peptidomics and targeted metabolomics to assess the biochemical alterations following the infection and to obtain a set of putative biomarkers useful for noninvasive diagnosis. We used an untargeted approach by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomics and peptidomics analysis and targeted LC-multiple reaction monitoring/MS for the analysis of amino acids. The levels of 77 proteins were significantly different in COVID-19 patients. Among these, seven proteins were found only in saliva from patients with COVID-19, four were up-regulated and three were down-regulated at least five-folds in saliva from COVID-19 patients in comparison to controls. The analysis of proteins revealed a complex balance between pro-inflammatory and anti-inflammatory proteins and a reduced amount of several proteins with immune activity that possibly favours the spreading of the virus. Such reduction could be related to the enhanced activity of endopeptidases induced by the infection that in turn caused an altered balance of free peptides. In fact, on a total of 28 peptides, 22 (80%) were differently expressed in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and control subjects. The multivariate analysis of such peptides permits to obtain a diagnostic algorithm that discriminate the two populations with a high diagnostic efficiency. Among amino acids, only threonine resulted significantly different between COVID-19 patients and controls, while alanine levels were significantly different between COVID-19 patients with different severity. In conclusion, the present study defined a set of molecules to be detected with a quick and easy method based on mass spectrometry tandem useful to reveal biochemical alterations involved in the pathogenesis of such a complex disease. Data are available via ProteomeXchange with identifier PXD045612.

Biologically Synthesized Gold Nanoparticles Mitigate Aluminum Chloride-Induced Nephrotoxicity via Downregulation of iNOX, LCN2 and IL-1β Genes.

Humans are constantly exposed to aluminum (Al), an environmental toxicant, and its accumulation in the glomerular could lead to acute kidney disease. Biologically synthesized gold nanoparticles (AuNPs) have been employed in the management of kidney disorders. This study assessed the modulatory effect of AuNPs mediated by Hibiscus sabdariffa (HS) on aluminum chloride (AlCl3)-induced nephrotoxicity in rats. Experimental rats were randomly distributed into six groups of seven animals each. Aluminum chloride (100 mg/kg bw) was orally given to the rats for 42 days to induce nephrotoxicity. Treatment with silymarin and HS-AuNPs lasted for 14 days. Serum kidney function, tissue arginase level and oxidative stress biomarkers, as well as tissue gene expression of inducible nitric oxide synthase (iNOS), lipocalin 2 (LCN2) and interleukin-1 beta (IL-1β) were evaluated. Exposure of AlCl3 to the rats produced a marked (p < 0.05) increase in the levels of serum urea and creatinine in comparison with the control. Similarly, tissue arginase and malondialdehyde (MDA) levels were also increased while a reduction in the activity of superoxide dismutase (SOD) and the levels of reduced glutathione (GSH) and nitric oxide (NO) were noted in the AlCl3-induced rats. Aluminum chloride also upregulated the mRNA expression of iNOS, LCN2 and IL-1β in the rats. These biochemical alterations were, however, attenuated by the administration of HS-AuNPs but the 5 mg/kg HS-AuNPs exhibited better anti-nephrotoxic activity than the 10 mg/kg dose, and could, thus serve as a potential dose for managing renal diseases.

Protective efficacy of thymoquinone against malathion-induced histopathological and biochemical alterations in the gills of Labeo rohita

Protective efficacy of thymoquinone against malathion-induced histopathological and biochemical alterations in the gills of Labeo rohita

Studies on morphological and biochemical alterations associated with drought tolerance in linseed

Studies on morphological and biochemical alterations associated with drought tolerance in linseed

Embryotoxicity and biochemical changes of clioquinol (CQ) and their impact on zebrafish (Danio rerio): An environmental safety concern

Antibiotic residues and their conversion into toxic products have the potential to place human health at risk and ecosystem, which is precisely the continued accumulation of antibiotics in the environment has greatly alarmed humans and aquatic animals. This work sought to assess the possible impacts of clioquinol (CQ) on hepatotoxicity, teratogenicity, and biochemical alterations in zebrafish adults and embryos. The study examined the acute toxicity of CQ treatment to zebrafish embryos, adults, and 96-hour post fertilisation (hpf), in addition to the teratogenicity of CQ to embryonic and sac-fry stages. The lethal toxicity indicates that the 96 h LC50 values of CQ treated with 48, 72, and 96- hpf larvae; adult fish were 4.78, 3.75, 2.69; 10.86, 8.75, and 6.55 mg/L. This finding implies that zebrafish were more susceptible to CQ in their early life stages than in their adult stages, which is in accordance with in silico analyses using ECOSAR and T.E.S.T. At doses of 5 mg/L or higher, CQ would suppress zebrafish embryonic motility, heart rate, hatching rate, and body length of surviving larvae. Furthermore, to pericardial oedema, CQ also resulted in morphological abnormalities, including tail, spine, and yolk sac oedema. Histopathological alterations were noted in the kidney, intestines, gills, liver, and brain. Glutathione-S-transferase, catalase, and superoxide dismutase levels in the adult zebrafish decreased in a dose-dependent manner following 96 h of treatment. In addition, the adult zebrafish exposed to CQ had significantly downregulated levels of SOD, growth hormone 1, and TNF-α in the liver and blood. The findings provided the foundation for further research into the mechanism behind CQ toxicity in zebrafish, as they demonstrated that CQ had notable detrimental effects on zebrafish at different life stages.

Drought stress enhances phytochemical, antioxidant, antidiabetic and anticancer properties in Pandanus tectorius

Global warming is responsible for increasing temperatures and reducing rainfall in many regions of the world. Due to insufficient rainfall or lack of water in the soil, plants experience a range of morphological and biochemical alterations when they are exposed to drought conditions. Interestingly, the cells of drought-stressed plants can serve as a potential source for discovering new drugs. These secondary metabolic products have important biological functions that determine how plants interact with the environment and help them accommodate alterations. Present research has shed light on the response of Pandanus tectorius induced drought stress at 8th and 16th days. The studies observed the levels of various secondary metabolites in plants under drought-induced stress. Among the secondary metabolites analyzed, total alkaloids exhibited the highest overall concentration at 26.19 ± 0.83a. Furthermore, the observations found that drought stress had a significant impact on the plant's secondary metabolism. This resulted in increased levels of total alkaloids, saponins, tannins, and phenolics compared to the control plant. Especially the concentration of phenolics showed the most significant increase, with a remarkable 64.99% rise observed at the 16th day of treatment. The concentration of phenolics reached (20.52 ± 0.181c) at this level. Moreover, compared to control, P. tectorius exhibits significant antioxidant, antidiabetic, anti-inflammatory, molecular docking, and anticancer effects against MDA-MB-231 human breast cancer cell line inhibitory concentration IC50 values (48.91 ± 0.95 μg/mL) at 16th day treated plants. Consequently, the positive responses of P. tectorius drought stress enhance secondary metabolites. This research focus on drought stress stimulus prompts an urge in the production of secondary metabolites in P. tectorius, leading to an increase in its anticancer and anti-diabetic properties and treatments for type-2 diabetes and against fighting for cancer with minimal side effects and helping prevent diseases.

Histological and Biochemical Alterations Underlying Statin-Associated Pancreatic Toxicity in a Rat Model

ObjectiveTo investigate the histological and biochemical alterations in the pancreas associated with statin-induced toxicity using a rat model. MethodologyA one-year laboratory-based experimental control trial conducted at department of anatomy of a public sector medical college in Rawalpindi, in collaboration with the National Institute of Health (NIH) Islamabad and Armed Forces Institute of Pathology (AFIP) Rawalpindi. Twenty male Sprague-Dawley rats were assigned to the control group and another twenty to the experimental group. For a duration of 12 weeks, the experimental group was given 60 mg/kg/day of simvastatin orally, whereas the control group was given water and a conventional diet. The following characteristics were measured: body weight, pancreatic weight, biochemical parameters (cytokines, enzymes), and histological alterations (congestion, necrosis, fibrosis). Version 23 of the Statistical Package for the Social Sciences (SPSS) program was used to analyze the data. Qualitative variables were expressed as percentages and frequencies. The statistical significance was defined as P &lt; 0.05. Chi-square analyses contrasted the qualitative factors among the groups. ResultsCompared to controls, the simvastatin group showed significantly increased mean pancreatic weight (p=0.043), congestion (55% vs 0%, p&lt;0.001), higher levels of CRP (p&lt;0.030), IL-6 (p&lt;0.040), and TNF-α (p&lt;0.040). Trends of mild necrosis (25% vs 5%, p=0.182) and interstitial fibrosis (15% vs 0%, p=0.231) were observed but not statistically significant. DiscussionThis work shows that simvastatin significantly affects the pancreatic histomorphology and biochemical parameters in rats. It causes a noticeable amount of necrosis, interstitial fibrosis, and changes the pancreatic biochemical profile. These changes raise the possibility of long-term statin-associated pancreatitis and endocrine/exocrine dysfunction. Using a stable animal model, these new findings offer distinctive insights into the impact of simvastatin on pancreatic morphology. Conclusion Simvastatin profoundly impacts pancreatic histomorphology, warranting further investigation into mechanisms of toxicity and close monitoring of patients for pancreatic adverse effects during statin therapy.

Protective Role of Melatonin Against Abamectin-Induced Biochemical, Immunohistochemical, and Ultrastructural Alterations in the Testicular Tissues of Rats.

Abamectin is one of the most widely used pesticides due to its strong insecticidal and anthelmintic activities. Melatonin is a neurohormone with potent antioxidant, anti-apoptotic, and anti-inflammatory effects. This study aimed to investigate the potential ameliorative effects of melatonin against abamectin-induced testicular toxicity in rats. Twenty-four rats were divided into four groups: control group (1 mL/kg/day corn oil), melatonin-treated group (10 mg/kg/day), abamectin-treated group (0.5 mg/kg/day), and melatonin plus abamectin-treated group. Test substances were administered via oral gavage once daily for 28 days. While MDA and 8-OHdG levels increased in the testicular tissue of rats treated with abamectin, SOD, CAT, GPx, and GST enzyme activities decreased significantly. While interleukin-17 levels, TNF-α, and caspase3 expression increased in the testicular tissue, acetylcholinesterase activity decreased. At the same time, serum gonadotropins (luteinizing and follicle-stimulating hormones) and testosterone levels decreased. Light microscope examinations of testicular tissues revealed severe histopathological changes, such as atrophic hyalinized seminiferous tubules, basement membrane irregularity, degeneration, spermatogenic cell loss, and necrosis. Electron microscopy examinations revealed large vacuoles in Sertoli and spermatogenic cells, swelling and vacuolization in mitochondria, lysosomal structures, and increased pyknotic nuclei. In contrast, melatonin supplementation significantly ameliorated abamectin-induced testicular toxicity in rats through antioxidant, antiapoptotic, and anti-inflammatory mechanisms.

A Natural Chalcone Cardamonin Inhibited Transformation of Aryl Hydrocarbon Receptor Through Binding to the Receptor Competitively.

Chalcones are widely present in most plants and have various health beneficial functions. This study investigates the suppressive effect of 13 natural and synthetic chalcones on transformation of aryl hydrocarbon receptor (AhR) induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (3-MC) in a cell-free system, Hepa-1c1c7 cells, and liver of ICR mice. In the cell-free system, cardamonin dose-dependently inhibits AhR transformation. Chalcones with substitution on 2' and/or 6' position is important for the suppressive effect, while the substitution on 4' position is negatively for the effect. Moreover, cardamonin and 2'-hydroxychalcone competitively inhibit the binding of [3H]-3-MC to the AhR. In Hepa-1c1c7 cells, cardamonin inhibits AhR transformation and expression of cytochrome P4501A1 (CYP1A1) in a dose-dependent manner through suppressing TCDD-induced phosphorylation of both AhR and AhR nuclear translocator, heterodimerization of them, and nuclear translocation of AhR. In the liver of mice, oral administered cardamonin also inhibits 3-MC-induced AhR translocation and expression of CYP1A1. Among used chalcones, a natural chalcone cardamonin competitively binds to AhR and suppresses its transformation. Thus, cardamonin is an effective food factor for suppression of the dioxin-caused biochemical alterations and toxicities.

Biochemical and Hematological Derangement in Plasmodium falciparum Infected Patients Attending Health Facilities in Northern Taraba State, Nigeria

Plasmodium falciparum predominates as the leading cause of malaria-related mortality, particularly in sub-Saharan Africa, posing a significant global health threat. This study aims to assess the hematological and biochemical alterations attributed to P. falciparum infection among patients seeking care in health facilities across Northern Local Government Areas of Taraba State, encompassing Jalingo, Lau, and Zing. A prospective cross-sectional study method was adopted and enrolled 1,500 participants who underwent testing for P. falciparum using Giemsa-stained blood film examination, Rapid Diagnostic Test (RDT), and Polymerase Chain Reaction (PCR). Hematological parameters, including Packed Cell Volume (PCV), white blood cell counts, and erythrocyte sedimentation rate (ESR), as well as biochemical markers such as albumin, bilirubin, and electrolyte levels, were assessed. Results shows that, out of 1,500 individuals, 304 were infected with P. falciparum, representing a prevalence of 20.3%. Significant differences were observed in hematological and biochemical parameters between infected and non-infected participants, including lower PCV and platelet counts, elevated neutrophil counts, and altered liver enzyme levels among parasitized individuals. The study also compared the diagnostic performance of RDT and microscopy, revealing variations in sensitivity and specificity. This study underscores the clinical utility of hematological and biochemical parameters in malaria management, particularly in resource-limited settings like Nigeria. The findings highlight the importance of comprehensive diagnostic approaches and suggest integrating these adjunct tools into malaria treatment protocols to enhance patient care and outcomes. Keywords: Malaria, Derangement, Haematological, Biochemical, Plasmodium falciparum