Bioimpacts最新文献

Introduction: The main objective of this research is to identify potential leads for developing potent Keap1 inhibitors.

Methods: In the current research article, in-silico methods have been employed to discover potential Keap1 inhibitors. 3D-QSAR was generated using the ChemBL database of Keap1 inhibitors with IC₅₀. The best pharmacophore was selected for the screening of three different libraries namely Asinex, MiniMaybridge, and Zinc. The molecules screened from the databases were filtered through druggability rules and molecular docking studies. The best binding molecules obtained after docking studies were subjected to physicochemical properties toxicity determination by in-silico methods. The best hits were studied for stability in the cavity of Keap1 by molecular dynamic simulations.

Results: The virtual screening of different databases was carried out separately and three leads, were obtained. These lead molecules ASINEX 508, MiniMaybridgeHTS_01719, and ZINC 0000952883 showed the best binding in the Keap1 cavity. The molecular dynamic simulations of the binding complexes of the leads support the docking analysis. The leads (ASINEX 508, MiniMaybridgeHTS_01719, and ZINC 0000952883) were stabilized in the Keap1 binding cavity throughout 100 ns simulation, with average RMSD values of 0.100, 0.114, and 0.106 nm, respectively.

Conclusion: This research proposes three lead molecules as potential Keap1 inhibitors based on high throughput screening, docking, and MD simulation studies. These hit molecules can be used for further design and development of Keap1 inhibitors. This research provides the preliminary data for discovering novel Keap1 inhibitors. It opens new avenues for medicinal chemists to explore antioxidant-stimulating molecules targeting the Keap1-Nrf2 pathway.

Introduction: The immunosuppressive context of the tumor microenvironment (TME) is a significant hurdle in breast cancer (BC) treatment. Combinational therapies targeting cancer core signaling pathways involved in the induction of TME immunosuppressive milieu have emerged as a potent strategy to overcome immunosuppression in TME and enhance patient therapeutic outcomes. This study presents compelling evidence that targeting hypoxia-inducible-factor-1 alpha (Hif-1α) alongside chemotherapy and immune-inducing factors leads to substantial anticancer effects through modulation of TME.

Methods: Chitosan (Cs)/Hif-1alpha siRNA nano-complex was synthesized by siRNA adsorption methods. Nanoparticles were fully characterized using dynamic light scattering and scanning electron microscope. Cs/Hif-1α siRNA cytotoxicity was measured by MTT assay. The anticancer effects of the combinational therapy were assessed in BALB/c bearing 4T1 tumors. qPCR and western blotting were applied to assess the expression of some key genes and proteins involved in the induction of immunosuppression in TME.

Results: Hif-1α siRNA was successfully loaded in chitosan nanoparticles. Hif-1α siRNA nanocomplexes significantly inhibited the expression of Hif-1α. Triple combination therapy (Paclitaxel (Ptx) + Imiquimod (Imq) + Cs/Hif-1α siRNA) inhibited tumor growth and downregulated cancer progression genes while upregulating cellular-immune-related cytokines. Mice without Cs/Hif-1α siRNA treatments revealed fewer cancer inhibitory effects and more TME immunosuppressive factors. These results suggest that the inhibition of Hif-1α effects synergize with Ptx and Imq to inhibit cancer progression more significantly than other combinational treatments.

Conclusion: Combining Hif-1α siRNA with Ptx and Imq is promising as a multimodality treatment. It has the potential to attenuate TME inhibitory effects and significantly enhance the immune system's ability to combat tumor cell growth, offering an inspiration of hope in the fight against BC.

Schizophrenia is a devastating chronic mental health illness which includes a complex set of symptoms like hallucination, illusion and delusion, and to manage, lifelong antipsychotic medications are needed. Schizophrenia affects 1% of the population worldwide, and to date, two different classes of antipsychotics, i.e., typical and atypical antipsychotics, are available in the market, and there is an urgent need for promising antipsychotic drugs. In this review, we focus on recently approved antipsychotics and then focus on different antipsychotic drugs under clinical trials. In this review, we first focus on lumateperone in detail, which was approved in December 2019 by the Food and Drug Administration (FDA) and simultaneously modulates serotonin, glutamate and dopamine neurotransmitters and is used at doses of 10.5-, 21- and 42 mg, which show mild adverse effects like constipation, sedation, somnolence and fatigue. This review also focuses on a few more emerging antipsychotics like brexpiprazole, brilaroxazine, roluperidone, F17464, pimavanserin (ACP-103), xanomeline, BI 409306, BI 425809 and MK-8189 which are under different phase of clinical trials and might get approved soon. Brexpiprazole and brilaroxazine act on dopamine receptors, whereas xanomeline, pimavanserin and roluperidone do not act on D2 receptors and manage the symptoms. All the antipsychotic drugs covered did not show any other severe adverse effects except gastrointestinal issues and cardiometabolic risk factors. However, still rigorous clinical trials and modifications are needed to manage adverse effects, and we can expect a few antipsychotics to be on the market soon.

Introduction: Multiple sclerosis (MS) is a chronic neuroinflammatory diseases characterized by demyelination of the nerve fibers. Immunogenic cell death (ICD) is a process, during which damaged and stressed cells release danger-associated molecular patterns (DAMPs) activating immune responses. This study aimed to elucidate the induction of ICD in MS diseases.

Methods: To achieve this goal, the level of DAMPs including Annexin A1 (ANXA1), calreticulin and HMGB1 was measured in the cerebrospinal fluid (CSF) of a secondary progressive multiple sclerosis (SPMS) patient in comparison to control group.

Results: Results showed significant upregulation (more than two-fold) of ANXA1, calreticulin (CRT) and HMGB1 in the CSF of the patient.

Conclusion: Although further studies are suggested in this regard, this data could imply induction of ICD in MS. The proposed ICD might trigger immune response against neural cells resulting in neuroinflammation and demyelination in CNS in MS. Our observation could suggest inclusion of ICD interfering treatments in routine MS therapy.

Introduction: Meniscus injuries in athletes' knee joints not only hinder performance but also pose substantial challenges in timely diagnosis and effective treatment. Delayed or inaccurate diagnosis often leads to prolonged recovery periods, exacerbating athletes' discomfort and compromising their ability to return to peak performance levels. Therefore, the accurate and timely diagnosis of meniscus injuries is crucial for athletes to receive appropriate treatment promptly and resume their training regimen effectively.

Methods: This paper presents a multi-step approach for diagnosing meniscus injuries through segmentation of images into lesions regions, followed by a combined classification method. The present study employs a method whereby image noise is first reduced, followed by the implementation of an enhanced iteration of the U-Net algorithm to perform image segmentation and identify regions of interest for potential injury detection.

Results: In the context of diagnosing injury images, the extraction of features was accomplished through the utilization of the contour line method. Furthermore, the identification of injury types was facilitated through the application of the ensemble method, employing the principles of basic category-based voting. The method under consideration has been subjected to evaluation using a well-recognized dataset comprising MRI images knee joint injuries.

Conclusion: The findings reveal that the efficacy of the proposed approach exhibits a significant enhancement in contrast to the newly developed techniques.

Introduction: Traumatic optic neuropathy (TON) is an acute visual dysfunction subsequent to head and neck trauma. Despite immense efforts, there is no effective treatment to minimize the damage caused by TON. Due to its anti-inflammatory and neuroprotective properties, we aimed to measure the effect of sumatriptan on optic nerve injury in rats.

Methods: Bulldog forceps were used to induce optic nerve crush. Immediately after trauma, a single dose of sumatriptan was intravitreally injected and rats were just observed for 1 week. Visual evoked potential (VEP) was recorded to assess optic nerve function on days 2, 5, and 7 after optic nerve injury. Retinas were extracted seven days after trauma to assess molecular and microscopic changes.

Results: Crushing force reduced cell survival, decreased the amplitude of the waves, and prolonged their latency in VEP. In contrast, sumatriptan significantly increased cell survival and shortened the latency of P2 and N2 waves. Likewise, sumatriptan significantly decreased the tissue levels of toll-like receptor 4 (TLR4), phosphorylated extracellular signal-regulated kinase (p-ERK), malondialdehyde (MDA), indole-amine 2,3-dioxygenase 1 (IDO), tumor necrosis factor α (TNF-α), interferon γ (INF-γ), and kynurenine in the retinas of rats.

Conclusion: These findings suggest that sumatriptan can enhance retinal cell viability, improve optic nerve function, and decrease inflammation, possibly through attenuation of TLR4, ERK, and kynurenine signaling pathways. Thus, future clinical trials should assess the efficacy of low-dose intravitreal sumatriptan for patients with TON.

Introduction: The current study reports the comparative stimuli-responsive synthesis of silver nanoparticles (AgNPs) with various sizes and morphologies employing Lycium ruthenicum extract and sodium citrate solutions.

Methods: The morphology and size of AgNPs were regulated by varying the pH values, concentrations of the extract solution, and temperatures in the reaction medium. The prepared AgNPs were assessed via various instrumental analyses, including UV-Vis, FTIR, XRD, TEM, and DLS.

Results: The L. ruthenicum extract displayed several functional groups that reduced the Ag ions to the AgNPs at different values of pH. However, the primary chemical structure of L. ruthenicum was virtually unaltered at these conditions. Variations in the pH and extract concentration of the reaction medium yielded AgNPs of different sizes and morphologies. Both bio- and chemo-synthesized AgNPs revealed a relatively dispersed sphere-shaped morphology under alkaline conditions (≈ 36 nm).

Conclusion: This study introduced a simple, valuable, and green technique for stimuli-sensitive AgNPs synthesis employing the L. ruthenicum extract.

Introduction: This study aimed to investigate the impact of a hydro-alcoholic solution containing kopexil on hair growth, and growth factors, and to evaluate its skin penetration, as well as its potential toxic effects on the liver and kidneys in animal models.

Methods: Animal studies were conducted on mice over 28 days, involving minoxidil (positive control), kopexil (test), and negative control groups. Morphological characteristics of skin and hair were assessed. Levels of hair growth-promoting markers (HGF and VEGF) were determined through western blot analysis. Toxic effects were examined by isolating and weighing the kidneys and livers, followed by histological examination.

Results: The kopexil group demonstrated significant increases in hair weight, follicle count, percentage of anagen hair, and hair growth compared to the minoxidil. Western blot analysis revealed higher expression levels of hair growth-promoting factors in the kopexil-treated group. No statistically significant differences in liver and kidney weights or noticeable morphological variations were observed in the toxicity tests across the groups.

Conclusion: The 5% (w/v) hydro-alcoholic solution containing kopexil proved to be an effective hair growth stimulator, influencing various factors. Its daily use can be considered a suitable treatment method for stimulating hair growth, given its improved effectiveness and ease of use for patients.

Psoriasis is a chronic condition that can strike at any age. This sickness is associated with inflammatory problems that impact all humans in the world. Psoriasis is more common in Scandinavians than in Asian and African populations due to a combination of factors such as age, gender, geographic location, ethnicity, genetic and environmental factors. Immune stimulation, genetic contribution, antimicrobial peptides, and other significant triggers such as medicines, immunizations, infections, trauma, stress, obesity, alcohol intake, smoking, air pollution, sun exposure, and particular disorders cause psoriasis. Numerous clinical research investigations are now underway, and therapeutic alternatives are available. However, these therapies only improve symptoms and do not accomplish a complete cure; they also have dangerous and undesirable side effects. Natural products have gained popularity recently due to their great effectiveness, safety, and low toxicity. Natural formulations of various nanocarriers like liposomes, lipospheres, nanogels, emulgel, nanostructured lipid carriers, nanosponge, nanofibers, niosomes, nanomiemgel, nanoemulsions, nanospheres, cubosomes, microneedles, nanomicelles, ethosomes, nanocrystals, and foams, have significantly contributed and encouraged advancement in psoriasis disease treatment. These phytochemical-loaded new nanoformulations address several issues associated with natural products in conventional dosage forms, such as instability, poor solubility, and limited bioavailability. This article reviews some of the intriguing phytochemicals, as well as their possible molecular target locations and mechanisms of action, which may assist in the development of more specific and selective antipsoriatic medicines. Exploring and understanding phytochemicals' functions will allow for more site-specific psoriasis treatment techniques. This review concluded the psoriasis disease with phytoconstituent loaded herbal or polyherbal nanocarriers and their mechanistic approach.

Introduction: The use of medicinal plants in the management of depression, also known as phytotherapy or herbal medicine for depression, is an area of growing interest in the field of mental health and complementary medicine.

Methods: This study used a systematic assessment of pertinent literature to assess the effectiveness of medicinal herbs in treating mild to severe depression. A comprehensive literature search was conducted to identify randomized controlled trials (RCTs) that reported data on the intervention, control group, adverse events, outcome measurements, and main findings. A summary and analysis were done on the included research data.

Results: We included 23 RCTs investigating the efficacy of herbal medicines, including Crocus sativus, Lavandula angustifolia, Melissa officinalis, and Echium amoenum, in treating depression. In general, saffron showed encouraging outcomes when used to treat mild to severe depression. With no discernible variations in the reported adverse effects, it proved to be equally efficacious as well-known antidepressants like imipramine and fluoxetine. However, it is noteworthy that not all trials yielded favorable results.

Conclusion: More investigation is required to fully understand the mechanisms of action, ideal dosage schedules, long-term effects, and relative efficacy of medicinal plants in depressive treatment.