Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.

From nature to nanotechnology: The interplay of traditional medicine, green chemistry, and biogenic metallic phytonanoparticles in modern healthcare innovation and sustainability.

As we navigate the modern era, the intersection of time-honoured natural remedies and contemporary scientific approaches forms a burgeoning frontier in global healthcare. For generations, natural products have been foundational to health solutions, serving as the primary healthcare choice for 80% to 85% of the world's population. These herbal-based, nature-derived substances, significant across diverse geographies, necessitate a renewed emphasis on enhancing their quality, efficacy, and safety. In the current century, the advent of biogenic phytonanoparticles has emerged as an innovative therapeutic conduit, perfectly aligning with principles of environmental safety and scientific ingenuity. Utilizing green chemistry techniques, a spectrum of metallic nanoparticles including elements such as copper, silver, iron, zinc, and titanium oxide can be produced with attributes of non-toxicity, sustainability, and economic efficiency. Sophisticated herb-mediated processes yield an array of plant-originated nanomaterials, each demonstrating unique physical, chemical, and biological characteristics. These attributes herald new therapeutic potentials, encompassing antioxidants, anti-aging applications, and more. Modern technology further accelerates the synthesis of natural products within laboratory settings, providing an efficient alternative to conventional isolation methods. The collaboration between traditional wisdom and advanced methodologies now signals a new epoch in healthcare. Here, the augmentation of traditional medicine is realized through rigorous scientific examination. By intertwining ethical considerations, cutting-edge technology, and natural philosophy, the realms of biogenic phytonanoparticles and traditional medicine forge promising pathways for research, development, and healing. The narrative of this seamless integration marks an exciting evolution in healthcare, where the fusion of sustainability and innovation crafts a future filled with endless possibilities for human well-being. The research in the development of metallic nanoparticles is crucial for unlocking their potential in revolutionizing fields such as medicine, catalysis, and electronics, promising groundbreaking applications with enhanced efficiency and tailored functionalities in future technologies. This exploration is essential for harnessing the unique properties of metallic nanoparticles to address pressing challenges and advance innovations across diverse scientific and industrial domains.

Mitigative potential of kaempferide against polyethylene microplastics induced testicular damage by activating Nrf-2/Keap-1 pathway.

Polyethylene microplastics (PE-MPs) are one of the environmental contaminants that instigate oxidative stress (OS) in various organs of the body, including testes. Kaempferide (KFD) is a plant-derived natural flavonol with potential neuroprotective, hepatoprotective, anti-cancer, anti-oxidant and anti-inflammatory properties. Therefore, the present study was designed to evaluate the alleviative effects of KFD against PE-MPs-prompted testicular toxicity in rats. Fourty eight adult male albino rats were randomly distributed into 4 groups: control, PE-MPs-administered (1.5 mgkg-1), PE-MPs (1.5 mgkg-1) + KFD (20 mgkg-1) co-treated and KFD (20 mgkg-1) only treated group. PE-MPs intoxication significantly (P < 0.05) lowered the expression of Nrf-2 and anti-oxidant enzymes, while increasing the expression of Keap-1. The activities of anti-oxidants i.e., catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), hemeoxygene-1 (HO-1) and glutathione peroxidase (GPx) were reduced, besides malondialdehyde (MDA) and reactive oxygen species (ROS) contents were increased significantly (P < 0.05) following the PE-MPs exposure. Moreover, PE-MPs exposure significantly (P < 0.05) reduced the sperm motility, viability and count, whereas considerably (P < 0.05) increased the dead sperm number and sperm structural anomalies. Furthermore, PE-MPs remarkably (P < 0.05) decreased steroidogenic enzymes and Bcl-2 expression, while increasing the expression of Caspase-3 and Bax. PE-MPs exposure significantly (P < 0.05) reduced the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, whereas inflammatory indices were increased. PE-MPs exposure also induced significant histopathological damages in the testes. Nevertheless, KFD supplementation significantly (P < 0.05) abrogated all the damages induced by PE-MPs. The findings of our study demonstrated that KFD could significantly attenuate PE-MPs-instigated OS and testicular toxicity, due to its anti-oxidant, anti-inflammatory, androgenic and anti-apoptotic potential.

Spirulina platensis ameliorates hepatic oxidative stress and DNA damage induced by aflatoxin B1 in rats.

Aflatoxin B1 (AFB1) is a widely distributed mycotoxin, causing hepatotoxicity and oxidative stress. One of the most famous unicellular cyanobacteria is Spirulina platensis (SP) which is well known for its antioxidant characteristics against many toxicants. Therefore, this study aimed to investigate the antioxidant potential and hepatoprotective ability of SP against oxidative stress and cytotoxicity in male Wistar albino rats intraperitoneally injected with AFB1. Rats were separated into five groups as follows: negative control administered with saline; SP (1000 mg/kg BW) for two weeks; AFB1 (2.5 mg/kg BW) twice on days 12 and 14; AFB1 (twice) + 500 mg SP/kg BW (for two weeks) and AFB1 (twice) + 1000 mg SP/kg BW (for two weeks). Liver and blood samples were assembled for histological and biochemical analyses. AFB1 intoxicated rats showed a marked elevation in serum biochemical parameters (ALP, ALT, and AST), hepatic lipid peroxidation (MDA and NO), and proliferating cell nuclear antigen (PCNA) indicating DNA damage. Moreover, AFB1 caused suppression of antioxidant biomarkers (SOD, GHS, GSH-Px, and CAT). However, the elevated serum levels of biochemical parameters and PCNA expression were reduced by SP. Moreover, SP lowered oxidative stress and lipid peroxidation markers in a dose-dependent manner. To sum up, SP supplementation is capable of decreasing AFB1 toxicity through its powerful antioxidant activity.

Marvels of Bacilli in soil amendment for plant-growth promotion toward sustainable development having futuristic socio-economic implications.

Microorganisms are integral components of ecosystems, exerting profound impacts on various facets of human life. The recent United Nations General Assembly (UNGA) Science Summit emphasized the critical importance of comprehending the microbial world to address global challenges, aligning with the United Nations Sustainable Development Goals (SDGs). In agriculture, microbes are pivotal contributors to food production, sustainable energy, and environmental bioremediation. However, decades of agricultural intensification have boosted crop yields at the expense of soil health and microbial diversity, jeopardizing global food security. To address this issue, a study in West Bengal, India, explored the potential of a novel multi-strain consortium of plant growth promoting (PGP) Bacillus spp. for soil bioaugmentation. These strains were sourced from the soil's native microbial flora, offering a sustainable approach. In this work, a composite inoculum of Bacillus zhangzhouensis MMAM, Bacillus cereus MMAM3), and Bacillus subtilis MMAM2 were introduced into an over-exploited agricultural soil and implications on the improvement of vegetative growth and yield related traits of Gylcine max (L) Meril. plants were evaluated, growing them as model plant, in pot trial condition. The study's findings demonstrated significant improvements in plant growth and soil microbial diversity when using the bacterial consortium in conjunction with vermicompost. Metagenomic analyses revealed increased abundance of many functional genera and metabolic pathways in consortium-inoculated soil, indicating enhanced soil biological health. This innovative bioaugmentation strategy to upgrade the over-used agricultural soil through introduction of residual PGP bacterial members as consortia, presents a promising path forward for sustainable agriculture. The rejuvenated patches of over-used land can be used by the small and marginal farmers for cultivation of resilient crops like soybean. Recognizing the significance of multi-strain PGP bacterial consortia as potential bioinoculants, such technology can bolster food security, enhance agricultural productivity, and mitigate the adverse effects of past agricultural activities.

Acute aflatoxin B1-induced hepatic and cardiac oxidative damage in rats: Ameliorative effects of morin.

Aflatoxins (AFs) are secondary metabolites produced by the fungus Aspergillus flavus, of which Aflatoxin-B1 (AFB1) appears to be the most cancerogenic and of the highest toxicity. AFB1 causes serious effects on several organs including the liver. Morin is a flavonol that exists in many fruits and plants and has diverse biological properties including anticancer, anti-atherosclerotic, antioxidant, anti-inflammatory, immunomodulatory, and multi-organ protective activities. The present study aims to evaluate the potential protective effects of morin against acute AFB1-induced hepatic and cardiac toxicity in rats. Forty rats were divided into five groups (n = 8) as follows: control received the vehicle, morin was orally administered 30/mg/kg body weight (MRN30), the AFB1 was administered orally at a dose of 2.5 mg/kg, twice on days 12 and 14 of the experiment for the 3rd, 4th, and 5th groups., AFB1-MRN15 was orally given morin at a dose of 15 mg/kg body weight, and AFB1-MRN30 orally received morin at 30 mg/kg body weight. The results indicated a significant decrease in serum AST, ALP, LDH, GGT, CK, CK-MB, 8-OHdG, IL-1ß, IL-6, TNF-a levels in MRN30 compared to AFB1, and AFB1-MRN15 groups. However, the results indicated non-significant differences in the serum levels between MRN30, control, and AFB1-MRN30 groups. Meanwhile, regarding the hepatic and cardiac parameters, there were significant differences in the levels of MDA, NO, GSH, GSH-Px, SOD, and CAT in MRN30 compared to AFB1, and AFB1-MRN15 groups, overall implying the protective effects of morin. To conclude, morin at a dose of 30 mg/kg b. wt. showed significant enhancements in acute AFB1-induced hepatic and cardiac toxicity in rats, which could play a role in limiting the public health hazards of AFs.

Chia seeds and coenzyme Q10 alleviate iron overload induced hepatorenal toxicity in mice via iron chelation and oxidative stress modulation.

Iron overload (IOL) can cause hepatorenal damage due to iron-mediated oxidative and mitochondrial damage. Remarkably, combining a natural iron chelator with an antioxidant can exert greater efficacy than monotherapy. Thus, the present study aimed to evaluate the efficacy of Chia and CoQ10 to chelate excess iron and prevent hepatorenal oxidative damage in IOL mice. Male Swiss albino mice (n = 49) were randomly assigned to seven groups: control, dietary Chia, CoQ10, IOL, IOL + Chia, IOL + CoQ10, and IOL + Chia + CoQ10. Computational chemistry indicates that the phytic acid found in the Chia seeds is stable, reactive, and able to bind to up to three iron ions (both Fe2+ and Fe3+). IOL induced a significant (P < 0.05) increase in serum iron, ferritin, transferrin, TIBC, TSI, RBCs, Hb, MCV, MCH, WBCs, AST, ALT, creatinine, and MDA. IOL causes a significant (P < 0.05) decrease in UIBC, platelets, and antioxidant molecules (GSH, SOD, CAT, and GR). Also, IOL elicits mitochondrial membrane change depolarization, and DNA fragmentation and suppresses mitochondrial DNA copies. Furthermore, substantial changes in hepatic and renal tissue, including hepatocellular necrosis and apoptosis, glomerular degeneration, glomerular basement membrane thickening, and tubular degeneration, were observed in the IOL group. Dietary Chia and CoQ10 induced significant (P < 0.05) amelioration in all the mentioned parameters. They can mostly repair the abnormal architecture of hepatic and renal tissues induced by IOL, as signified by normal sinusoids, normal central veins, and neither glomerular damage nor degenerated tubules. In conclusion, the combined treatment with Chia + CoQ10 exerts more pronounced efficacy than monotherapy in hepatorenal protection via chelating excess iron and improved cellular antioxidant status and hepatorenal mitochondrial function in IOL mice.

Integrated approach to hydrogeochemical appraisal of groundwater quality concerning arsenic contamination and its suitability analysis for drinking purposes using water quality index.

Arsenic (As), contamination in drinking groundwater resources is commonly environmental problem in many developing countries including Pakistan, with significant human health risk reports. In order to examine the groundwater quality concerning As contamination, its geochemical behavior along with physicochemical parameters, 42 samples were collected from community tube wells from District Bahawalpur, Punjab, Pakistan. The results showed the concentration of elevated As, its source of mobilization, and associated public health risk. The As concentration detected in groundwater samples varied from 0.12 to 104 µg/L with an average value of 34.7 µg/L. Among 42 groundwater samples, 27 samples were beyond the permitted limit of 10 µg/L recommended by World Health Organization (WHO), for drinking purposes. Statistical analysis result show that the groundwater cations values are in decreasing order such as: Na+ > Mg2+ > Ca2+ > K+, while anions were HCO3- > SO42- > Cl- > NO3-. Hydrochemical facies result depict that the groundwater samples of the study area, 14 samples belong to CaHCO3 type, 5 samples belong to NaCl type, 20 samples belong to Mixed CaMgCl type, and 3 samples belong to CaCl2 type. It can be accredited due to weathering and recharge mechanism, evaporation processes, and reverse ion exchange. Gibbs diagram shows that rock water interaction controls the hydrochemistry of groundwater resources of the study area. Saturation Index (SI) result indicated the saturation of calcite, dolomite, gypsum, geothite, and hematite mineral due their positive SI values. The principal component analysis (PCA) results possess a total variability of 80.69% signifying the anthropogenic and geogenic source of contamination. The results of the exposure-health-risk-assessment method for measuring As reveal significant potential non-carcinogenic risk (HQ), exceeding the threshold level of (> 1) for children in the study area. Water quality assessment results shows that 24 samples were not suitable for drinking purposes.

Unveiling a novel terpolymer-metal complex: A detailed exploration of synthesis, characterization, and its potential as an antimicrobial and antioxidant agent.

In an innovative approach to push the boundaries of antimicrobial and antioxidant strategies, we present the synthesis and characterization of a novel terpolymer derived from N-Phenyl-p-phenylenediamine and 2-aminopyrimidine with formaldehyde in the presence of dimethylformamide as a reaction medium through polycondensation technique. Leveraging this terpolymer as a ligand, we introduce an intriguing terpolymer-metal complex, created with Ni (II) metal ion. In our pursuit to validate the structure and properties of these substances, we performed meticulous characterizations using important spectral studies such as FTIR, electronic, and 1H NMR spectroscopy. This provided us with a unique fingerprint for the (N-Phenyl-p-phenylenediamine-2-aminopyrimidine-formaldehyde) terpolymeric ligand (PAF) and its metal complex. In addition, the molecular weights of PAF terpolymer were established using gel permeation chromatography. Upon investigation, PAF terpolymer and PAF-Ni complex exhibited impressive antimicrobial activity, tested by the disc-diffusion technique. Both demonstrated potency against a range of harmful bacterial and fungal strains, including Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger. In an extension to their biological applications, we evaluated the free radical scavenging activity of PAF terpolymer and PAF-Ni complex using the DPPH assay. The complex PAF-Ni showcased an enhanced scavenging activity 73.94% (IC50 = 17.58) compared to the ligand PAF 63.06% (IC50 = 27.61) at 100 µg/ml indicating its potential role in oxidative stress management.

Harnessing role of sesamol and its nanoformulations against neurodegenerative diseases.

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.

Life table study of Sitotroga cerealella on different cereals and its implications on the performance of the egg parasitoid (Trichogramma chilonis) under laboratory conditions.

Sitotroga cerealella is one of the major pests of cereals in the field and storage conditions throughout the world. The main objective was to study the life tables of S. cerealella on wheat, maize and barley and its implications on percent parasitism of Trichogramma chilonis. S. cerealella is reared under lab conditions as its eggs are utilized for rearing T. chilonis. Fresh eggs of S. cerealella were collected and after hatching the neonate larvae of S. cerealella were transferred onto each host plant species for obtaining first (F1) generation (G). Seventy eggs were used for each host and each egg was used as a replicate. Daily observations were made for recording the life-table parameters of the S. cerealella. The data showed that the developmental time of S. cerealella eggs and pupae was maximum (5.68 and 7.75 days) when reared on wheat, while the maximum larval duration (19.77 days) of S. cerealella was recorded on barley. The maximum fecundity (290.30 ± 22.47 eggs/female) was recorded on maize, while minimum fecundity per female was recorded on barley (159.30 eggs/ female). The S. cerealella reared on maize had significantly higher values of finite rate of increase (λ), intrinsic rate of increase (r), and net reproductive rate (Ro) (0.14 ± 0.04 day- 1, 1.16 ± 0.05 day- 1, and 136.85 ± 20.25 eggs/ female) respectively. The mean generation time (T) (35.18 ± 0.61 days) was higher on wheat. Likewise, the gross reproductive rate (GRR) and the age-stage specific reproductive values (vxj) of newly oviposited eggs of S. cerealella were recorded higher (136.85 ± 20.25; 1.160 offspring) on maize. The data regarding the efficacy of T. chilonis for different parameters were recorded higher on maize i.e., percent parasitism (89.00 ± 2.30%), percent adult emergence (81.60 ± 1.20%), adult longevity (3.80 ± 0.10 days) and total adult longevity (9.90 ± 0.20 days) as compared to wheat and barley. Our findings revealed that S. cerealella can be best reared on maize under laboratory conditions as it prefers this host as compared to wheat and barley. Therefore, assigning the most susceptible and favorite host (maize) would help us to improve T. chilonis mass production under laboratory conditions.

Effect of larval diets on the life table parameters of dengue mosquito, Aedes aegypti (L.) (Diptera: Culicidae) using age-stage two sex life table theory.

The current study regarding the effects of larval diets on the life table parameters of dengue mosquitoes, Aedes aegypti was conducted under laboratory conditions at 27 ± 2 °C and 60 ± 5% relative humidity at NIFA (Nuclear Institute for Food and Agriculture) Peshawar, Pakistan. The data on life table parameters of Ae. aegypti reared on Diet 1 (replacement diet), Diet 2 (Khan's diet for Anopheles), Diet 3 (Khan's modified diet) and Diet 4 (IAEA diet) were analyzed using the age-stage, two-sex life table software. Diet 4 (IAEA) was used as a control for comparison. The results indicated that significantly maximum percentage of egg hatching of Ae. aegypti was observed when reared on Diet 4 (73.86%) and Diet 3 (72.90%), while less % of egg hatching was recorded in Diet 1 (40.67%) and Diet 2 (55.53%). The data further showed that the Diet 3 had a highest intrinsic rate of increase (r) (0.097 ± 5.68 day-1), finite rate of increase (λ) (1.10 ± 6.26 day-1) and net reproductive rate (R0) (11.99 ± 1.52 eggs/female) followed by Diet 2 and Diet 4. The mean generation time (T) of Ae. aegypti reared on Diet 3 (23.67 ± 0.86 days) and Diet 1 (24.05 ± 0.61 days) was significantly shorter than Diet 2 (26.15 ± 0.71 days) and Diet 4 (26.41 ± 0.38 days). The overall results revealed that Diet 3 showed good results at different life table parameters of Ae. aegypti and can be used as the preferred diet in the Sterile Insect Technique (SIT) where the mass culture of mosquitoes is required.

Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents.

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus.

Theoretical design for covering Engeletin with functionalized nanostructure-lipid carriers as neuroprotective agents against Huntington's disease via the nasal-brain route.

Objective: To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington's disease (HD). Methods: We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability. Results: HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain's motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD. Conclusion: The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.

Bromelain mitigates liver fibrosis via targeting hepatic stellate cells in vitro and in vivo.

Various therapeutic approaches are conducted for regression of liver fibrosis and prevent possible further carcinogenic transformation. This study was aimed to assess the prospective therapeutic potential of bromelain against thioacetamide (TAA)-induced liver fibrosis using in-vitro and in vivo approaches. In vitro study, HSC-T6 cell line was used to evaluate the effect of bromelain on HSC-T6 cell viability and apoptosis. In vivo, Rats were treated by TAA for 6 weeks for induction of hepatic fibrosis followed by post treatment by different doses of bromelain and silymarin for further 4 weeks to assess the regression of hepatic fibrosis. The in-vitro findings indicated that bromelain hindered the proliferation of HSCs in concentration dependent manner compared with the untreated cells. The in vivo study revealed that treatment of TAA fibrotic rats with different doses of bromelain and silymarin induced a significant restoration in liver function biomarkers, attenuation of oxidative stress, upregulation of total antioxidant capacity and thereby decline of fibrotic biomarkers and improving histopathological and immunohistochemical changes. In conclusion, This study indicates that bromelain can regress TAA induced hepatic fibrosis in rats via inhibiting HSCs activation, α-SMA expression and the ECM deposition in hepatic tissue in addition to its antioxidants pathway, these findings prove the promising therapeutic potential of bromelain as a novel therapeutic approach for chronic hepatic fibrotic diseases.

Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer's sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer's disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity. RESULT: In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex's dynamic development. CONCLUSION: As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD.

Unveiling Curvularia tuberculata-induced leaf anomalies in Rhododendron ferrugineum: implications in cultural-ecological conservation and harnessing microbial intervention in socio-economic advancement.

Introduction: The research focuses on Rhododendron ferrugineum L., Nepal's national flower and Uttarakhand's state tree, thriving in high-altitude mountain ecosystems. Methodology and Result: A study conducted in Himachal Pradesh (Latitude: N 31° 6' 2.0088", Longitude: E 77° 10' 29.9136") identified leaf anomalies resembling rust-like manifestations in R. ferrugineum. These anomalies were traced back to the pathogenic fungus Curvularia tuberculata, marking the first documented case of its impact on R. ferrugineum in India. Discussion: This discovery emphasizes the need for vigilant monitoring, disease management research, and conservation efforts to protect the cultural and ecological significance of this iconic shrub. Beyond its immediate findings, the study introduces a novel dimension to Indian flora by associating C. tuberculata with R. ferrugineum, historically linked to monocotyledonous crops. The research methodology combines traditional microscopic examination with advanced genomic sequencing and phylogenetic analysis, enhancing pathogen identification accuracy. Future prospect: In a broader context, this research aligns with the United Nations Sustainable Development Goals (SDGs) by highlighting the importance of environmental preservation, conservation, and sustainable management. It underscores the intricate interplay between biodiversity, cultural heritage, and the need for holistic solutions. Overall, this study calls for proactive measures to protect R. ferrugineum's cultural and ecological heritage and emphasizes the significance of interdisciplinary approaches in addressing emerging ecological threats.

Application of Green Technologies in Design-Based Extraction of Celastrus paniculatus (Jyotishmati) Seeds, SEM, GC-MS Analysis, and Evaluation for Memory Enhancing Potential.

Background: The Celastrus paniculatus (CP), commonly known as Jyotishmati, is considered as "elixir of life" by Indian people for the prevention or management of many ailments. The seed powder and its extract have widely used commercially for the preparation of various Ayurvedic formulations for the improvement of memory. CP seeds were generally extracted by conventional extraction methods (CEMs) which are assumed to impact environment burden and also produce low extract yield. Green extraction with possible improvement in extract yield has always been the need of hour for selected medicinal plant. Objective: In the present research, we aimed to optimize the different extraction factors in microwave and ultrasound-based extraction. The various extracts obtained in conventional and green methods are also evaluated for the possible improvement in memory enhancing potential. Materials and Methods: The selected medicinal herb was extracted by CEM (maceration and percolation). In green methods such microwave-assisted extraction (MAE) and ultrasound assisted-extraction (UAE), various parameters were optimized using Box-Behnken design coupled with response surface methodology. The scanning electron microscopy (SEM) and gas chromatography-mass spectroscopy (GC-MS) analyses were also done to confirm the possible improvement in concentration of plant actives. The Swiss albino mice were used to evaluate memory enhancing potential of different extracts. Results: At the optimized conditions MAE and UAE the extraction yield, total phenolic content (TPC) and Total flavonoid content (TFC) are significantly improved. The GC-MS analysis further confirms the improvement in concentration of certain fatty acid esters, pilocarpine, and steroidal compounds in optimized extracts. The optimized extracts also exhibited the significant improvement in behavioral parameters, oxidative stress-induced parameters, and acetylcholinesterase inhibitory potential. Discussion and Conclusion: From the results, we can say that the application of green technologies in design-based extraction of selected herb not only significantly reduces the extraction time but also improves the extract yield and concentration of plant actives. In nutshell, it can be concluded that the green approaches for extraction of seeds of Celastrus paniculatus could be scale up at a commercial level to meet the rising demand for herbal extract.

Chemometric Investigation and Antimicrobial Activity of Salvia rosmarinus Spenn Essential Oils.

To ensure the better production and sustainable management of natural resources, a chemometric investigation was conducted to examine the effect of cooperative and harvesting periods on the crop yields and chemical compositions of Salvia rosmarinus Spenn essential oils in the Oriental region of Morocco. The samples were collected from three cooperatives over nine time periods from January 2018 to April 2019. The chemical composition of Salvia rosmarinus Spenn essential oils was analyzed by gas chromatography coupled with mass spectrometry. The data from this study were processed by multivariate analyses, including principal component analysis (PCA) and hierarchical cluster analysis (HCA). The disc diffusion technique and a determination of the minimal inhibitory concentration were performed to study the antibacterial properties of the oils. Statistical analysis showed that the cooperative and harvest period have a significant effect on yields. The highest yield of essential oil was recorded in April 2019 at cooperative C1. The PCA and the HCA results were divided into two groups: Group A for the summer season and group B for the winter season. The samples collected during summer were characterized by a high amount of 1,8-cineole component and a high yield of essential oil, whereas the samples collected during winter were qualified by a high amount of α-pinene component and a low yield of essential oil. The antibacterial activity of Salvia rosmarinus Spenn essential oils showed that Mycobacterium smegmatis ATCC23857 and Bacillus subtilis ATCC 23857 are the most susceptible strains, stopping growth at 1/500 (v/v). The least susceptible strain is Escherichia coli ATCC25922, with an MIC value corresponding to 1/250 (v/v). The findings of this study could have a positive economic impact on the exploitation of rosemary in the Oriental region, especially during the best harvest periods, as they indicate how to obtain the best yields of oils richest in 1,8-cineole and α-pinene chemotypes.

Assessment of Contributing Factors and Treatment Practices for Therapeutic Efficacy and Drug-Related Problems in Suicidal Psychotic Patients.

Suicide, a deliberate act of self-harm with the intention to die, is an emerging health concern but, unfortunately, the most under-researched subject in Pakistan, especially in Khyber Pukhtunkhwa (KPK). In this study, we aimed to identify risk factors that can be associated with suicidal behavior (SB) and to evaluate the prevailing treatment practices for therapeutic efficacy and drug-related problems (DRPs) in psychotic patients among the local population of KPK. A prospective, multicenter study was conducted for suicidal cases admitted to the study centers by randomized sampling. Socio-demographics and data on suicidal behavior were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), socioeconomic condition by Kuppuswamy socioeconomic scale (KSES) and treatment adherence by Morisky Medication-Taking Adherence Scale (MMAS-4). Drug-related problems and the therapeutic efficacy of prevailing treatment practices were assessed at baseline and follow-up after 3 months of treatment provided. Regarding suicidality (N = 128), females reported more ideations (63.1%), while males witnessed more suicidal behavior (66.6%, p < 0.001). Suicide attempters were mostly married (55.6%, p < 0.002); highly educated (53.9%, p = 0.004); dissatisfied with their life and had a previous history (p < 0.5) of suicide attempt (SA) (20.6%), self-injurious behavior (SIB) (39.7%) and interrupted (IA) or aborted attempts (AA) (22.2%). A greater improvement was observed in patients receiving combination therapy (p = 0.001) than pharmacotherapy (p = 0.006) or psychotherapy (p = 0.183), alone. DRPs were also detected, including drug-selection problems (17.88%), dose-related problems (20.64%), potential drug−drug interactions (24.31%), adverse drug reactions (11.46%) and other problems like inadequate education and counseling (21.55%). Furthermore, it was also found that psychotic patients with suicidal ideations (SI) were significantly (p = 0.01) more adherent to the treatment as compared to those with suicidal attempts. We concluded that suicide attempters differed significantly from patients with suicidal ideations in psychotic patients and presented with peculiar characteristics regarding socio-demographic factors. A combination of therapies and adherence to the treatment provided better outcomes, and targeted interventions are warranted to address drug-related problems.