Structural and Dynamical Basis of VP35-RBD Inhibition by Marine Fungi Compounds to Combat Marburg Virus Infection.

The Marburg virus (MBV), a deadly pathogen, poses a serious threat to world health due to the lack of effective treatments, calling for an immediate search for targeted and efficient treatments. In this study, we focused on compounds originating from marine fungi in order to identify possible inhibitory compounds against the Marburg virus (MBV) VP35-RNA binding domain (VP35-RBD) using a computational approach. We started with a virtual screening procedure using the Lipinski filter as a guide. Based on their docking scores, 42 potential candidates were found. Four of these compounds-CMNPD17596, CMNPD22144, CMNPD25994, and CMNPD17598-as well as myricetin, the control compound, were chosen for re-docking analysis. Re-docking revealed that these particular compounds had a higher affinity for MBV VP35-RBD in comparison to the control. Analyzing the chemical interactions revealed unique binding properties for every compound, identified by a range of Pi-cation interactions and hydrogen bond types. We were able to learn more about the dynamic behaviors and stability of the protein-ligand complexes through a 200-nanosecond molecular dynamics simulation, as demonstrated by the compounds' consistent RMSD and RMSF values. The multidimensional nature of the data was clarified by the application of principal component analysis, which suggested stable conformations in the complexes with little modification. Further insight into the energy profiles and stability states of these complexes was also obtained by an examination of the free energy landscape. Our findings underscore the effectiveness of computational strategies in identifying and analyzing potential inhibitors for MBV VP35-RBD, offering promising paths for further experimental investigations and possible therapeutic development against the MBV.

Fabrication and optimization of naringin-loaded MOF-5 encapsulated by liponiosomes as smart drug delivery, cytotoxicity, and apoptotic on breast cancer cells.

INTRODUCTION: Cancers are regarded as hazardous due to their high worldwide death rate, with breast cancer (BC), which affects practically all cancer patients globally, playing a significant role in this statistic. The therapeutic approach for BC has not advanced using standard techniques, such as specialized naringin (NG) chemotherapy. Instead, a novel strategy has been utilized to enhance smart drug delivery (SDD) to tumors. SIGNIFICANCE: Herein, we established NG-loaded zinc metal-organic framework-5 (NG-MOF-5) coated with liponiosomes (LNs) to manufacture NG-MOF-5@LNs nanoparticles (NPs) for antibacterial and cancer treatment. METHODS: MOF-5, NG, and NG-MOF-5@LNs were evaluated with XRD, thermogravimetric analysis (TGA), FTIR, SEM, TEM, PDI, ZP, encapsulation efficiency (EE), loading efficiency (LE), and drug release (DR) kinetics. We examined the antibacterial activity involving minimum inhibitory concentration (MIC) and zone of inhibition by NG, MOF-5, and NG-MOF-5@LNs. The cell viability, necrosis, and total apoptosis (late and early) were evaluated for anti-cancer activity against MCF-7 BC cells. RESULTS: TEM results demonstrated that NG-MOF-5@LNs formed monodispersed spherical-like particles with a size of 122.5 nm, PDI of 0.139, and ZP of +21 mV. The anti-microbial activity results indicated that NG-MOF-5@LNs exhibited potent antibacterial effects, as evidenced by inhibition zones and MIC values. The Higuchi model indicates an excellent fit (R2 = 0.9988). The MTT assay revealed anti-tumor activity against MCF-7 BC cells, with IC50 of 21 µg/mL for NG-MOF-5@LNs and demonstrating a total apoptosis effect of 68.2% on MCF-7 cells. CONCLUSION: NG-MOF-5@LNs is anticipated to show as an effective antimicrobial and novel long-term-release antitumor agent and might be more suitable for MCF-7 cell therapy.

Leek (Allium ampeloprasum var. kurrat) aqueous extract loaded on selenium nanoparticles protects against testis and brain injury induced by mercuric chloride in rats.

BACKGROUND: Mercuric chloride (HgCl2) is poisonous to humans and animals and typically damages the nervous system and other organs. Mercuric chloride exposition disclosed to initiation of oxidative stress pathway can result in a defect in male fertility and testis tissue. Synthesized selenium nanoparticles (SeNPs) were characterized with a diameter range minimal than 100 nm, having the effective sets of the biological matter. The present study aimed to evaluate the effect of biosynthesized SeNPs, prepared by leek extract on Wistar rats' testicles and brain. METHODS: Thirty-five Wistar male rats (120-150 g) were randomly split into five groups (n = 7), orally ingested with leek aqueous extract loaded on SeNPs, and then the animals were administered with mercury II chloride (HgCl2) to induce testis injury and damage the nervous system. RESULTS: The used dose of mercuric chloride led to oxidative stress damage in the testis of the rats which was evidenced by a decrease in testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and proliferating cell nuclear antigen (PCNA) levels, and an increase in nuclear factor-kappa B (NF-κB) and caspase-3. Also, HgCl2 decreased the levels of dopamine (DA), serotonin (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in the brains of rats. In addition, A decrease was observed in the levels of antioxidant markers, B-cell lymphoma-2 (Bcl-2), as well as an increase in malondialdehyde (MDA), nitric oxide (NO), NF-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and Bax in both testes and brains. Pre-treatment with leek extract loaded on SeNPs significantly ameliorated testosterone, LH, FSH, PCNA and caspase-3 levels in the testis and DA, 5-HT, NE and BDNF in brains. Although the contents of MDA, NO, TNF-α, IL-1ß, NF-κB and Bax decreased significantly in both. glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and Bcl-2 levels were significantly improved in both organs. CONCLUSION: Our findings suggest that treatment with aqueous leek extract loaded on SeNPs may offer promising prospects for the advancement of anti-inflammation activity against testis injury and also have a very key role in neurobehavioral alterations as a result of mercury toxicity. © 2024 Society of Chemical Industry.

Biological Activities of Sargassum Algae Mediated ZnO and Co Doped ZnO Nanoparticles as Enhanced Antioxidant and Anti-Diabetic Agents.

Brown macroalgae (BMG) were used as carriers for ZnO (ZnO/BMG) and cobalt-doped ZnO (Co-ZnO/BMG) via facile microwave-assisted hydrothermal synthesis. The multifunctional structures of synthesized composites were evaluated as enhanced antioxidant and anti-diabetic agents based on the synergistic effects of ZnO, Co-ZnO, and BMG. BMG substrate incorporation and cobalt doping notably enhanced the bioactivity of the synthesized ZnO nanoparticles. As an antioxidant, the Co-ZnO/BMG composite exhibited highly effective scavenging properties for the common free reactive oxygen radicals (DPPH [89.6 ± 1.5%], nitric oxide [90.2 ± 1.3%], ABTS [87.7 ± 1.8%], and O2●- [46.7 ± 1.9%]) as compared to ascorbic acid. Additionally, its anti-diabetic activity was enhanced significantly and strongly inhibited essential oxidative enzymes (porcine α-amylase (90.6 ± 1.5%), crude α-amylase (84.3 ± 1.8%), pancreatic α-glucosidase (95.7 ± 1.4%), crude intestinal α-glucosidase (93.4 ± 1.8%), and amyloglucosidase (96.2 ± 1.4%)). Co-ZnO/BMG inhibitory activity was higher than that of miglitol, and in some cases, higher than or close to that of acarbose. Therefore, the synthetic Co-ZnO/BMG composite can be used as a commercial anti-diabetic and antioxidant agent, considering the cost and adverse side effects of current drugs. The results also demonstrate the impact of cobalt doping and BMG integration on the biological activity of ZnO.

Berberine enhances the sensitivity of radiotherapy in ovarian cancer cell line (SKOV-3).

Berberine, a well-known isoquinoline alkaloid derivative, has a varied range of pharmacological effects. Herein, we notice the radio-modulatory outcome of berberine in cultured ovarian cancer (SKOV-3) cells exposed to γ-rays as radiotherapy (RT). Cells pre-treated with berberine were irradiated by γ-irradiation and the liberation of reactive oxygen species (ROS) was analyzed by flow cytometry. Apoptotic cell death along with the DNA damage associated with protein expressions was projected by flow cytometry and confocal microscopy. Experimental findings established that berberine might be a capable radiosensitizer for treating SKOV-3, because of oxidative DNA damage. Moreover, the in-silico study of the compound, berberine suggests free energy of binding (ΔG) -7.5 kcal/mol with SKOV-3 and -8.8 kcal/mol of PALB/BRCA2, which proves an effective and compact binding of the complex and is safe for future clinical trials. Thus, our approach is probably to widen the field of study of SKOV-3 and PALB/BRCA2 from the inhibition of these targets as a prospective nutraceutical for the anti-cancer theragnostic candidate.

Influence of KISS1 gene polymorphisms on the risk of polycystic ovary syndrome and its associated variables, in Saudi women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder, affecting millions of women worldwide. The role of genetic polymorphisms of the KISS1 gene on the development of PCOS is still obscure. This study was designed to investigate the probable influence of KISS1 gene polymorphisms on PCOS and its associated variables: BMI, waist-hip ratio, kisspeptin, LH, FSH, and LH-FSH ratio. METHODS: The study comprised 104 PCOS women and 109 controls, with age ranging from 19 to 36 years. BMI, waist-hip ratio, and circulating levels of kisspeptin, LH, and FSH were measured. DNA was extracted, and genotyping of the KISS1 gene was carried out by nucleotide sequencing. The PCOS-associated variables were analyzed in different genotypes of single nucleotide polymorphisms (SNPs) of the KISS1 gene. RESULTS: The values of waist-hip ratio (WHR), LH, and LH-FSH ratio were significantly higher in PCOS women than controls. BMI, kisspeptin, and FSH levels exhibited no significant difference between the groups. Six novel SNPs of KISS1 gene were identified. Three: rs372790354G > A, rs12998G > A, and rs35431622A > T were investigated. Among these SNPs, the genotype and allele frequencies of rs372790354 showed significant association with PCOS (GA: p = 0.018, AA: p = 0.022, mutant allele-A: p = 0.021) and the G allele was protective. The values of LH, kisspeptin, and WHR of PCOS women were significantly influenced (p < 0.05) by the AA genotype of rs372790354. The other two SNPs rs12998G > A and rs35431622A > T revealed no significant influence on PCOS and associated variables. Haplotypes were constructed, but there was no significant difference between the patients and controls. CONCLUSION: In conclusion, this is the first study, which reports a significant influence of KISS1 gene polymorphism (rs372790354G > A) on PCOS and its associated variables. However, more extensive research is necessary to confirm these findings.

Exploring the therapeutic potential of lipid-based nanoparticles in the management of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a highly malignant and invasive tumor with significant mortality and morbidity. Current treatment modalities such as surgery, radiotherapy, and chemotherapy encounter significant limitations, such as poor targeting, systemic toxicity, and drug resistance. There is an urgent need for novel therapeutic strategies that offer targeted delivery, enhanced efficacy, and reduced side effects. The advent of lipid-based nanoparticles (LNPs) offers a promising tool for OSCC therapy, potentially overcoming the limitations of current therapeutic approaches. LNPs are composed of biodegradable and biocompatible lipids, which minimize the risk of toxicity and adverse effects. LNPs can encapsulate hydrophobic drugs, improving their solubility and stability in the biological environment, thereby enhancing their bioavailability. LNPs demonstrate significantly higher ability to encapsulate lipophilic drugs than other nanoparticle types. LNPs offer excellent storage stability, minimal drug leakage, and controlled drug release, making them highly effective nanoplatforms for the delivery of chemotherapeutic agents. Additionally, LNPs can be modified by complexing them with specific target ligands on their surface. This surface modification allows the active targeting of LNPs to the tumors in addition to the passive targeting mechanism. Furthermore, the PEGylation of LNPs improves their hydrophilicity and enhances their biological half-life by reducing clearance by the reticuloendothelial system. This review aims to discuss current treatment approaches and their limitations, as well as recent advancements in LNPs for better management of OSCC.

Synthesis and Biological Activity Evaluations of Green ZnO-Decorated Acid-Activated Bentonite-Mediated Curcumin Extract (ZnO@CU/BE) as Antioxidant and Antidiabetic Agents.

Green ZnO-decorated acid-activated bentonite-mediated curcumin extract (ZnO@CU/BE) was prepared as a multifunctional antioxidant and antidiabetic agent based on the extract of curcumin, which was used as a reducing and capping reagent. ZnO@CU/BE showed notably enhanced antioxidant properties against nitric oxide (88.6 ± 1.58%), 1,1-diphenyl-2-picrylhydrazil (90.2 ± 1.76%), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (87.3 ± 1.61%), and superoxide (39.5 ± 1.12%) radicals. These percentages are higher than the reported values of ascorbic acid as a standard and the integrated components of the structure (CU, BE/CU, and ZnO). This signifies the impact of the bentonite substrate on enhancing the solubility, stability, dispersion, and release rate of the intercalated curcumin-based phytochemicals, in addition to enhancing the exposure interface of ZnO nanoparticles. Therefore, effective antidiabetic properties were observed, with significant inhibition effects on porcine pancreatic α-amylase (76.8 ± 1.87%), murine pancreatic α-amylase (56.5 ± 1.67%), pancreatic α-glucosidase (96.5 ± 1.07%), murine intestinal α-glucosidase (92.5 ± 1.10%), and amyloglucosidase (93.7 ± 1.55%) enzymes. These values are higher than those determined using commercial miglitol and are close to the values measured using acarbose. Hence, the structure can be applied as an antioxidant and antidiabetic agent.

Biological characterization of microwave based synthesized ZnO and Ce doped ZnO nanoflowers impeded chitosan matrix with enhanced antioxidant and anti-diabetic properties.

The chitosan matrix was used as a substrate for ZnO nanoflowers (ZnO/CH) and Ce-doped ZnO nanoflowers (Ce-ZnO/CH) by microwave-induced hydrothermal synthesis processes. The obtained hybrid structures were assessed as enhanced antioxidant and antidiabetic agents considering the synergetic effect of the different components. The integration of chitosan and cerium induced significantly the biological activity of ZnO flower-like particles. Ce-doped ZnO nano-flowers show higher activities than both ZnO nanoflowers and ZnO/CH composite reflecting the strong effect of surface electrons that were formed by the doping process as compared to the high interactive interface of the chitosan substrate. As an antioxidant the synthetic Ce-ZnO/CH composite achieved remarkable scavenging efficiencies for DPPH (92.4 ± 1.33 %), nitric oxide (95.2 ± 1.81 %), ABTS (90.4 ± 1.64 %), and superoxide (52.8 ± 1.22 %) radicals which are significantly higher values than Ascorbic acid as standard and the commercially used ZnO nanoparticles. Also, its antidiabetic efficiency enhanced greatly achieving strong inhibition effects on porcine α-amylase (93.6 ± 1.66 %), crude α-amylase (88.7 ± 1.82 %), pancreatic α-glucosidase (98.7 ± 1.26 %), crude intestinal α-glucosidase (96.8 ± 1.16 %), and amyloglucosidase (97.2 ± 1.72 %) enzymes. The recognized inhibition percentages are notably higher than the determined percentages using miglitol drug and slightly higher than acarbose. This recommends the Ce-ZnO/CH composite as a potential antidiabetic and antioxidant agent compared with the high cost and the reported side effects of the commonly used chemical drug.

An Extensive Examination of the Warning Signs, Symptoms, Diagnosis, Available Therapies, and Prognosis for Lumpy Skin Disease.

The lumpy skin disease virus (LSDV) infects cattle and buffalo and causes lumpy skin disease (LSD). It affects the lymph nodes of the sick animals, causing them to enlarge and appear as lumps (cutaneous nodules) that are 2-5 cm in diameter on their heads, necks, limbs, udders, genitalia, and perinea. A high temperature, a sharp drop in milk supply, discharge from the eyes and nose, salivation, a loss of appetite, depression, damaged hides, and emaciation are further warning signs and symptoms. As per the Food and Agriculture Organization (FAO), the incubation period, or the time between an infection and symptoms, is approximately 28 days. Infected animals can transfer the virus by direct contact with the vectors, direct virus secretion from mouth or nose, shared feeding and watering troughs, and even artificial insemination. The World Organization for Animal Health (WOAH) and the FAO both warn that the spread of illnesses could lead to serious economic losses. This illness reduces cow's milk production because oral ulcers make the animal weak and lead them to lose their appetite. There are many diagnostics available for LSDV. However, very few tests yield accurate findings. The best methods for preventing and controlling the lumpy skin condition include vaccination and movement restrictions. As a specific cure is not available, the only available treatment for this illness is supportive care for cattle. Recently, India has developed a homologous, live-attenuated vaccine, Lumpi-ProVacInd, which is specifically intended to protect animals against the LSD virus. This study's primary goal is to accumulate data on symptoms, the most accurate method of diagnosis, treatments, and controls to stop infections from spreading as well as to explore future possibilities for the management of LSDV.

Lagerstroemia speciosa Ameliorated Blood Pressure in LNAME Induced Hypertension in Experimental Rats through NO/cGMP and Oxidative Stress Modulation.

Cardiovascular disease is the primary reason for chronic heart diseases and mortality worldwide. Hypertension (HTN) is the utmost dominant risk factor for the evolution of several diseases. Herbal medicines, traditional medicinal herbs, and their extracts are widely utilized to treat and monitor HTN. Herbal components have been shown to help relax arteries and lower oxidative stress. The current study assesses the probable role of herbal plant extract Lagerstroemia speciosa (LS) in the LNAME induced HTN in rats. LNAME (50 mg/100 mL) in drinkable water was given to rats for five weeks. There was a significant upsurge in LNAME-treated hypertensive rats' blood pressure (BP). On treatment with LS, it ameliorates blood pressure. Further, LS also improved body weight, reduced heart weight, and heart hypertrophy. The NO/cGMP concentration was lowered along with a substantial upsurge in the level of glutathione and a decline in MDA level. The LS extract also reduced the inflammatory cytokine markers in the systemic circulation. In conclusion, thus, the extract of LS treatment can efficiently alleviate the BP, oxidative stress markers, and inflammation and improve NO/cGMP concentration in LNAME induced HTN in rats.

Venom of the desert black snake Walterinnesia aegyptia enhances anti-tumor immunity via its beneficial modulatory effects on pro- and anti-tumorigenic inflammatory mediators in cultured colon cancer cells.

The role of inflammation in colon cancer is understood as a well-accepted factor that has the tendency to release multiple pro- and anti-tumorigenic inflammatory mediators. Inflammation-induced increased expression of anti-tumorigenic inflammatory mediators and decreased expression of pro-tumorigenic inflammatory mediators encourage beneficial inflammatory effects in terms of powerful anti-tumor immunity. The present study aims to screen the beneficial inflammatory effects of Walterinnesia aegyptia venom via determining its modulatory tendency on the expression of 40 pro- and anti-tumorigenic inflammatory mediators (cytokines/growth factors/chemokines) in LoVo human colon cancer cell line. LoVo-cells were treated with varying doses of crude venom of W. aegyptia. Cell viability was checked utilizing flow cytometry, and IC50 of venom was determined. Venom-induced inflammatory effects were evaluated on the expression of 40 different inflammatory mediators (12 anti-tumorigenic cytokines, 11 pro-tumorigenic cytokines, 7 pro-tumorigenic growth factors, 9 pro-tumorigenic chemokines and 1 anti-tumorigenic chemokine) in treated LoVo-cells [utilizing enzyme-linked immunosorbent assay (ELISA)] and compared with controls. Treatment of venom induced significant cytotoxic effects on inflamed LoVo-cells. IC50 treatment of venom caused significant modulations on the expression of 22 inflammatory mediators in treated LoVo-cells. The beneficial modulatory effects of venom were screened via its capability to significantly increase the expression of five powerful anti-tumorigenic mediators (IL-9, IL-12p40, IL-15, IL-1RA and Fractalkine) and decrease the expression of four major pro-tumorigenic mediators (IL-1ß, VEGF, MCP-1 and MCP-3). Walterinnesia aegyptia venom-induced beneficial modulations on the expression of nine crucial pro/anti-tumorigenic inflammatory mediators can be effectively used to enhance powerful anti-tumor immunity against colon cancer.