Significant Side Effects Research Articles

Clinical Pharmacology Of Selective Oestrogen Receptor Modulators In The Prevention Of Breast Cancer, Osteoporosis, Coronary Heart Disease, Alzheimer's Disease, Use In Hormone Replacement Therapy, Cholesterol Metabolism

Oestrogen is the key regulatory hormone for the development and maintenance of reproductive functions and affects various physiological systems, including the skeletal, cardiovascular, and central nervous systems. oestrogen replacement therapy (ERT) is highly effective in postmenopausal women, addressing menopausal symptoms and providing beneficial effects on osteoporosis and coronary heart disease. However, ERT is associated with significant side effects, such as an increased risk of breast cancer. To mitigate these risks, selective oestrogen receptor modulators (SERMs) have been developed. SERMs are a growing class of synthetic nonsteroidal compounds that act as oestrogen receptor agonists or antagonists in a tissue-specific manner. They can selectively activate or inhibit oestrogen receptors in different tissues throughout the body. SERMs are used to treat a variety of conditions, including ER-positive breast cancer, osteoporosis, coronary heart disease, Alzheimer’s disease, and cholesterol metabolism disorders in postmenopausal women. Specific SERMs are employed for different conditions: raloxifene for osteoporosis, tamoxifen and toremifene for breast cancer, clomiphene for the induction of ovulation, and ormeloxifene for oral contraception. Arzoxifene is used for altering cholesterol metabolism. Each SERM forms a unique complex with oestrogen receptors, influencing target tissues and resulting in a tissue-selective pharmacological profile. This unique mechanism of action translates into specific safety and efficacy profiles for each SERM. The surprising pharmacology of SERMs has sparked interest in developing new selective medications, allowing for precise treatment of various diseases. This article reviews the pharmacological properties of SERMs and explains how they differ from oestrogen in their actions.

The Efficacy of Ginger in Reducing Post-Spinal Puncture Shivering in Cesarean Section Patients: A Randomized Clinical Trial

BackgroundPostoperative shivering is a common and unpleasant complication of spinal puncture. Various pharmacologic and non-pharmacologic options have been studied to control shivering. This study aimed to evaluate the effectiveness of ginger in treating post-spinal puncture shivering in patients undergoing cesarean section. MethodsA placebo-controlled, single-blinded, randomized controlled trial was conducted. A total of 242 eligible participants were assigned to the ginger or placebo suppository groups using block randomization. Suppositories were administered immediately after the operation. The shivering scores were recorded for both groups at six time points (20, 35, 50, 65, 80, and 95 minutes) after the intervention. The participants' shivering scores were analyzed using a repeated-measures analysis of variance (ANOVA) test. ResultsThe results showed significant differences between the two groups in the mean shivering scores at 20, 35, 50, 65, and 80 minutes (P < 0.05), with no significant difference at 90 minutes. The trend of changes at six time points demonstrated that shivering intensity significantly differed between the two groups over time (P < 0.001). No significant side effects were observed in patients in the two groups. ConclusionGinger suppository reduces shivering after spinal puncture in patients undergoing CS. Due to the lack of side effects and lower cost of ginger suppositories, it can be considered as an option for post-CS shivering.

Genomics in active surveillance and post-prostatectomy patients: A review of when and how to use effectively.

Prostate cancer (PCa) represents a significant health burden globally, ranking as the most diagnosed cancer among men and a leading cause of cancer-related mortality. Conventional treatment methods such as radiation therapy or radical prostatectomy have significant side effects which often impact quality of life. As our understanding of the natural history and progression of PCa has evolved, so has the evolution of management options. Active surveillance (AS) has become an increasingly favored approach to the management of very low, low, and properly selected favorable intermediate risk PCa. AS permits ongoing observation and postpones intervention until definitive treatment is required. There are, however, challenges with selecting patients for AS, which further emphasizes the need for more precise tools to better risk stratify patients and choose candidates more accurately. Tissue-based biomarkers, such as ProMark, Prolaris, GPS (formerly Oncotype DX), and Decipher, are valuable because they improve the accuracy of patient selection for AS and offer important information on the prognosis and severity of disease. By enabling patients to be categorized according to their risk profiles, these biomarkers help physicians and patients make better informed treatment choices and lower the possibility of overtreatment. Even with their potential, further standardization and validation of these biomarkers is required to guarantee their broad clinical utility. Active surveillance has emerged as a preferred strategy for managing low-risk prostate cancer, and tissue-based biomarkers play a crucial role in refining patient selection and risk stratification. Standardization and validation of these biomarkers are essential to ensure their widespread clinical use and optimize patient outcomes.

Reducing COVID-19-Induced Educational Slumps—Training Preservice Teachers to Be Children Coaches: An Evaluation of Effects in Elementary Schools

The school closures due to the COVID-19 pandemic have had significant side effects, particularly on the psychological well-being of pupils. This situation poses great challenges for teachers in schools. At the same time, teacher education students have to be prepared for this situation by being trained to deal with difficult situations and pupils with symptoms of psychological disorders. Furthermore, they need to adequately address the increasing heterogeneity in terms of their pupils’ learning standards. To meet these challenges, the teaching project “CaBire” was called into being. As part of this project, teacher education students first receive theoretical input to act as socio-psychological coaches for children. After the training phase, students offer support to pupils at schools. This practical phase is accompanied by coaching-supervision seminars led by psychology teachers at the university. Both the practical phase, as well as the accompanying seminars at the university can be credited to teacher education students’ studies. Here we report a good-practice example and an evaluation of this teaching concept based on data of a mixed-method design. The results are promising and point towards a beneficial program for both teacher education students and pupils.

Comparison of effects of dexmedetomidine with ketofol and ketofol alone on quality of sedation in pediatric patients undergoing magnetic resonance imaging: A prospective randomized controlled double-blind trial

Background and Aim: Patient movement during magnetic resonance imaging (MRI) is the most frequent cause of artifacts and poor scan quality. Children cannot lie still. Thus, anesthesia is required to keep the child calm and immobile. This randomized double-blinded clinical trial compares the clinical effects of the addition of dexmedetomidine as premedication with ketofol on the quality of sedation. We hypothesized that the addition of dexmedetomidine would improve the quality of sedation. Methods: A total of 132 children aged 6 months to 10 years were randomized into groups DK (dexmedetomidine–ketofol) and K (ketofol). DK received an intravenous bolus of dexmedetomidine (0.5 mcg/kg) as premedication 10 minutes prior. Both the groups were induced with ketofol (0.5 mg/kg), and sedation was maintained with propfol infusion (100 mcg/kg/min). The primary objective was the quality of sedation as assessed by the University of Michigan Sedation Scale. Image quality, requirement of rescue propofol dose, recovery, and adverse events were also studied. Data are given as median [interquartile range (IQR)] or frequency. Results: All 132 children completed MRI scans. The DK group showed significantly better quality of sedation, 71% versus 47% of children, a median difference of 1 (-0.569 to -0.0969), P &lt; .005, a better quality of scan, a reduced number of additional doses of propofol, and a decreased total dose of propofol. Hemodynamic parameters and recovery times for the two groups were similar. There were no significant side effects in both groups. Conclusion: The quality of sedation and the quality of the MRI scan are greatly improved by administering dexmedetomidine (0.5 mcg/kg) 10 minutes before to induction. Additionally, this technique decreases the need of propofol and gives better hemodynamic stability without delaying the recovery time.

Correlation Between Reduced IL-1β Levels in Acne Lesions and the Decrease in Acne Inflammatory Lesions Following Topical Vitamin D Administration: A Double-Blind Randomized Controlled Trial.

The inflammatory process in acne vulgaris (AV) is characterized by the upregulation of specific pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8, within sebocytes and keratinocytes. Sebocytes have been identified as target cells for bioactive vitamin D. Experimental studies on animal models have demonstrated the potent comedolytic effects of topical vitamin D. However, further research is required to specifically evaluate the impact of vitamin D on inflammatory lesions in acne vulgaris (AV). To evaluate the effectiveness of topical vitamin D in treating acne vulgaris (AV) lesions by investigating its anti-inflammatory effects on pro-inflammatory cytokine modulation, specifically assessing the correlation between IL-1β levels in acne lesions and the reduction in AV severity. This study is a double-blind, randomized, placebo-controlled clinical trial with a 2-arm design over an 8-week intervention period. Participants were randomly assigned to either the topical vitamin D group (cholecalciferol 50 mcg) or the topical placebo group, with each group comprising 32 subjects. All participants received concomitant treatment with topical adapalene 0.1%. Cytokine levels within acne lesions were assessed using Luminex Polystyrene Screening Assays to detect and quantify IL-1β levels. The effectiveness of the treatment was evaluated by monitoring the reduction in the number of inflammatory lesions, while the safety of topical vitamin D was assessed by documenting and analyzing any reported side effects. The study found a significant correlation between the reduction in IL-1β levels within acne lesions and the decrease in moderate and severe inflammatory lesions in acne vulgaris (p = 0.028). The topical application of vitamin D led to a significant reduction in inflammatory AV lesions (p = 0.045). No significant topical side effects were observed in either the vitamin D or placebo groups. This study demonstrates that the topical administration of vitamin D in acne vulgaris (AV) lesions is effective in reducing pro-inflammatory cytokine levels within acne lesions and in decreasing the severity of AV. NCT05758259. September 5, 2022.

A Precision Engineered Interleukin-2 for Bolstering CD8+ T- and NK-cell Activity without Eosinophilia and Vascular Leak Syndrome in Nonhuman Primates.

SAR-444245 (SAR'245, pegenzileukin) is an extended half-life IL-2 that targets effector CD8+ T and NK cells, with little effect on regulatory T cells. We show that in the nonhuman primate model that closely approximates human immune function and response to IL-2, SAR'245 selectively activates CD8+ T and NK effectors without significant serious side effects (vascular leak syndrome or cytokine release syndrome), suggesting its potential for the treatment of solid tumors in humans.

Phage cocktail inhibits inflammation and protects the integrity of the intestinal barrier in dextran sulfate sodium-induced colitis mice model

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by abdominal pain, diarrhea, and rectal bleeding. This study aims to explore the protective effects of a phage cocktail (108 PFU/mL of Clostridium perfringens phage, 108 PFU/mL of Escherichia coli phage, and 108 PFU/mL of Salmonella phage) on a mouse colitis model induced by dextran sulfate sodium (DSS) and its potential toxic effects on normal mice. The results demonstrate that the phage cocktail significantly alleviates clinical symptoms in mice, reduces colon shortening, weight loss, and colonic pathological damage. Furthermore, the phage cocktail markedly suppresses the inflammatory response and safeguards intestinal barrier integrity in the colonic tissues of the mouse colitis model. Preliminary investigation of the toxic effects of the phage cocktail in mice indicates that continuous administration for 14 days does not yield statistically significant differences in hematological and blood biochemical parameters, and specific pathological changes are absent in histopathological examination results. The aforementioned findings suggest that the phage cocktail exhibits anti-inflammatory and intestinal barrier protective effects in the mouse colitis model, and it does not exert significant toxic side effects on mice.

Efficacy and safety of different pharmacological interventions in the treatment of tardive dyskinesia: a systematic review and network meta-analysis.

The aim of this study is to indirectly compare and rank the different drugs that have been studied in randomized clinical trials (RCTs) in patients with tardive dyskinesia (TD) in terms of their efficacy in ameliorating the symptoms of TD and safety. A network meta-analysis and a systematic review were registered prospectively on PROSPERO under the ID: CRD42023407823 and were conducted in accordance with the PRISMA-NMA guidelines. PubMed, Scopus, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Sciences, and Clinicaltrials.gov were searched to identify relevant records. Any parallel randomized blinded controlled clinical trials that studied the use of any medications in treating TD and assessed the symptoms using a functional scale that has been previously validated. The standardized mean difference of improvement along with the reported adverse events for each drug was extracted from each trial, and a network meta-analysis was conducted using a random-effects model. One thousand eight hundred seventeen patients in 33 RCTs were included in the analysis. Twenty-three different drugs were compared to placebo in terms of reduction in TD symptoms. Among these, valbenazine 80mg (SMD = - 1.66, 95%CI = [- 2.55; - 0.78]), valbenazine 40mg (- 1.00, [- 1.89; - 0.11]), and vitamin E (- 0.77, [- 1.45; - 0.1]) significantly reduced TD symptoms in comparison to placebo, while deutetrabenazine 36mg (- 1.00, [- 2.12; 0.11]) and reserpine (- 0.54, [- 1.09; 0.02]) did not significantly reduce symptoms. Some serious adverse events were reported for valbenazine and deutetrabenazine, which included mainly psychiatric symptoms such as depression, worsening of schizophrenia, and suicidal ideation, while mild adverse events were reported for other drugs, and their incidence in the treatment arms was comparable to those in the placebo arm. Valbenazine (80 and 40mg) and vitamin E demonstrated efficacy in treating tardive dyskinesia. However, the significant side effects of valbenazine should prompt further investigation of alternative treatment modalities.

Effect of Clozapine and Olanzapine on the Expression of Selected Genes and Epigenetic Regulators of Insulin Resistance Pathway in Human Preadipocytes – a Preliminary Study

Clozapine and olanzapine, popular second-generation antipsychotics used for various psychiatric disorders, cause significant side effects such as metabolic syndrome, but the exact mechanism remains unclear. The present study aimed to assess clozapine and olanzapine effects on the expression of mRNA insulin pathway genes (IRS-1, PTEN, PIK3CG and PIK3R1), microRNAs (miR-152-3p, miR-214-3p, miR-15b-5p, miR-16-5p, miR-126-3p) and long non-coding RNAs (lncRNAs: XIST, H19, SNHG16, PVT1), in human visceral preadipocytes (HPAd). Expression was examined by real - time PCR. Cell viability was determined by MTT assay. The findings revealed that in HAPd, both clozapine and olanzapine (at doses of 5 µM and 25 µM) decreased IRS-1 gene expression after 24 hours. After 48 hours, IRS-1 expression was reduced by clozapine at both concentrations and olanzapine at 5 µM. In addition, olanzapine (at 25 µM) decreased the expression of PIK3CG, miR-152-3p, miR-214-3p, miR-15b-5p and miR-16-5p after 24 hours, while increasing the expression of miR-126-3p at 5 µM. Clozapine at 25 µM decreased miR-16-5p expression and increased SNHG16 lncRNA expression at 5 µM after 24 hours. After 48 hours, olanzapine (at 25 µM) increased PIK3R1 expression and decreased PIK3CG expression at 5 µM. Both drugs at 5 µM increased the expression of miR-152-3p, miR-214-3p, miR-15b-5p and miR-16-5p after 48 hours, with clozapine further increasing the expression of miR-126-3p at this concentration. The results suggest that clozapine and olanzapine may affect the expression of key genes and epigenetic molecules in the insulin pathway, which is one potential cause leading to insulin resistance in adipose tissue.

Gemcitabine: Association with Thrombocytosis

Gemcitabine is a pyrimidine antimetabolite that affects DNA synthesis in the S-phase of the cell cycle. It is effective against cancers such as ovarian carcinoma, non-small cell lung cancer, and pancreatic cancer. However it causes significant side effects like myelosuppression, which leads to thrombocytopenia in about 71% of patients, prompting discontinuation of therapy. Even though thrombocytopenia is common, some patients experience thrombocytosis during Gemcitabine therapy, especially in the second and third cycles, possibly due to a rebound effect. Thrombocytosis is usually asymptomatic and occasionally leads to venous thrombosis, but its clinical significance is uncertain because of conflicting studies. Further research is required to understand the physiology behind thrombocytosis in Gemcitabine-treated patients. Fluctuations between thrombocytosis and thrombocytopenia need to be closely monitored. Management for Gemcitabine-induced thrombocytosis can be improved if more comprehensive studies are undertaken to explore the role of thrombocytosis in cardiovascular events.

The Effectiveness of 4% Niacinamide in A Case of Cutaneous Lupus

Background: Niacinamide, also called nicotinamide, is the active form of niacin (nicotinic acid, vitamin B3). Niacinamide’s role in medicine continues to be studied due to its extensive effects and low toxicity. Various studies also suggest that niacinamide offers anti-inflammatory effects, improves the skin barrier, and acts as an anti-aging, brightening, and anticancer agent. Cutaneous lupus (CL) is a general term for a group of autoimmune connective tissue disorders affecting the skin that may be associated with systemic lupus erythematosus (SLE). There are plenty of treatment modalities for patients with CL, each with varying efficacy. Therapeutic options for CL can range from topical agents, including corticosteroids and calcineurin inhibitors, to systemic therapy, such as antimalarials, immunosuppressants, retinoids, thalidomide, and biological agents. Niacinamide is a topical agent widely used in various cases, one of which is CL. Objective: This case report aims to discuss the effectiveness of niacinamide as an adjuvant therapy in CL. Case Presentation: A 48-year-old woman with SLE and CL received systemic therapy consisting of methylprednisolone, hydroxychloroquine, and 4% niacinamide gel for 8 weeks. Results: Observations showed clinical improvement in CL lesions without any significant side effects. Conclusion: Therefore, 4% niacinamide gel therapy can be used as an adjuvant therapy.

Oral Tranexamic Acid for Prevention and Treatment of Postinflammatory Hyperpigmentation.

Postinflammatory hyperpigmentation (PIH) is a skin disorder characterized by hyperpigmentation resulting from heightened inflammation and/or damage to the basement membrane, melanocytes, and keratinocytes, leading to abnormal and excessive pigment deposition. Oral tranexamic acid (TXA), originally used as an antifibrinolytic for managing excessive bleeding, has garnered attention for its demonstrated safety and efficacy in treating melasma. There is a growing body of evidence regarding the use of TXA in the treatment of PIH. To review the mechanism of action of oral TXA in treating PIH and examine the use of oral TXA in preventing and/or treating PIH associated with laser-based and light-based treatments in individuals with skin color. Review of relevant articles from 2000 to present found in the Cochrane Library, PubMed, Embase, and Google Scholar, regarding the use of oral TXA in the treatment of PIH. Studies reviewed investigated the efficacy of oral tranexamic acid (TXA) in treating postinflammatory hyperpigmentation (PIH) and use in preventing PIH when used in conjunction with other treatments. All studies demonstrated significant improvement in PIH without significant adverse effects and side effects. Oral tranexamic acid is emerging as a safe and effective treatment in the prevention and treatment of postinflammatory hyperpigmentation.

Anti-inflammatory and Restorative effects of milk exosomes and Dexamethasone-Loaded exosomes in a corneal alkali burn model

Corneal alkali burn is a common and challenging ocular trauma, necessitating the use of dexamethasone (DXMS) as a therapeutic agent. However, prolonged and frequent administration of this drug can lead to undesirable side effects, limiting its clinical application. This study aimed to investigate the role and mechanism of action of exosomes as drug carriers in corneal alkali burn repair. We employed centrifugation to isolate milk exosomes (EXO) as nanocarriers. We observed that EXO enhanced the activity and migration of corneal epithelial cells, expediting the repair process following corneal injury. Additionally, a nano-drug delivery model (DXMS@EXO) was designed using ultrasound to load DXMS into exosomes, thus enabling targeted delivery to inflammatory cells and enhancing drug efficacy. DXMS@EXO inhibited the inflammatory processes in the corneal alkali burn model by modulating the classical Wnt signaling pathway, thereby promoting corneal re-epithelialization and wound healing and accelerating the repair process of corneal alkali burn. Neither EXO nor DXMS@EXO exhibited significant side effects during the course of treatment. This study highlighted the substantial potential of EXO and DXMS@EXO in improving drug efficacy and facilitating the repair of corneal alkali burn.

Inflammatory pain resolution by mouse serum-derived small extracellular vesicles

Current treatments for chronic pain have limited efficacy and significant side effects, warranting research on alternative strategies for pain management. One approach involves using small extracellular vesicles (sEVs), or exosomes, to transport beneficial biomolecular cargo to aid pain resolution. Exosomes are 30–150 nm sEVs that can be beneficial or harmful depending on their source and cargo composition. We report a comprehensive multi-modal analysis of different aspects of sEV characterization, miRNAs, and protein markers across sEV sources. To investigate the short- and long-term effects of mouse serum-derived sEVs in pain modulation, sEVs from naïve control or spared nerve injury (SNI) model male donor mice were injected intrathecally into naïve male recipient mice. These sEVs transiently increased basal mechanical thresholds, an effect mediated by opioid signaling as this outcome was blocked by naltrexone. Mass spectrometry of sEVs detected endogenous opioid peptide leu-enkephalin. sEVs from naïve female mice have higher levels of leu-enkephalin compared to male, matching the analgesic onset of leu-enkephalin in male recipient mice. In investigating the long-term effect of sEVs, we observed that a single prophylactic intrathecal injection of sEVs two weeks prior to induction of the pain model in recipient mice accelerated recovery from inflammatory pain after complete Freund’s adjuvant (CFA) injection. Our exploratory studies examining immune cell populations in spinal cord and dorsal root ganglion using ChipCytometry suggested alterations in immune cell populations 14 days post-CFA. Flow cytometry confirmed increases in CD206+ macrophages in the spinal cord in sEV-treated mice. Collectively, these studies demonstrate multiple mechanisms by which sEVs can attenuate pain.

Effect of Hydralcoholic Extract of Dafneh on Expressin Level of MAPK8 and PTK2 Genes and Cell Viability of Ovarian Cancercell Lines (A2870S)

Introduction: Ovarian cancer, as an aggressive epithelial tumor, remains one of the leading causes of cancer-related mortality in women. Regarding to the side effects of chemical drugs, medicinal plants, according to their unique properties such as cheapness, naturalness and availability, and without any significant side effects, medicinal plants have recently been considered in the prevention of diseases. In this laboratory research, the cytotoxic effect of hydroalkolic extract of Daphne mucronata Royle on cell viability of A2780 cancer cell and the expression of MAPK8 and PTK2 genes in the cells treated with the Ephedra plant extract during three-time interval 24,48 and 72 hours after treatment were investigated. Methods: The inhibitory effect of hydroalcholic extact of D. mucronato on targeted cells was done using MTTassay then, expression level of MAPK8 and PTK2 genes in cells treated with plant extract were investigated using qRT-PCR method. Data analyses were done using GraphPad prism software. Results: Regarding to the results of cell viability, IC50 rate for 24, 48 and 72h after treatment were determined as 105.40, 85.98 and 81.38µg/mL, respectively. Expression analysis of tested genes showed that hydroalcoholic plant extract of D. mucronato had not significant effect on expression of targeted genes (Pvalue≤0.05) so that there was no significant difference on their expression level compared to the control. Conclusion: According to the results, it can be concluded that D. mucronato extract had a significant inhibitory effect on treated A2870s cancer cells, but it was not able to change the expression level of genes involved in anticancer activities and its molecular pathways. The use of bio-markers and other gene pathways is suggested for additional studies.

CAR-T-Cell Therapy for Systemic Lupus Erythematosus: A Comprehensive Overview.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by the production of autoreactive B and T cells and cytokines, leading to chronic inflammation affecting multiple organs. SLE is associated with significant complications that substantially increase morbidity and mortality. Given its complex pathogenesis, conventional treatments for SLE often have significant side effects and limited efficacy, necessitating the exploration of novel therapeutic strategies. One promising approach is the use of chimeric antigen receptor (CAR)-T-cell therapy, which has shown remarkable success in treating refractory hematological malignancies. This review provides a comprehensive analysis of the current use of CAR-T-cell therapy in SLE.

Bacopa monnieri confers neuroprotection by influencing signaling pathways associated with interleukin 4, 13 and extracellular matrix organization in Alzheimer's disease: A proteomics-based perspective

Alzheimer's disease, a prevalent neurodegenerative disorder in the elderly, is characterized by the accumulation of senile plaques and neurofibrillary tangles, triggering oxidative stress, neuroinflammation, and neuronal apoptosis. Current therapies focus on symptomatic treatment rather than targeting the underlying disease-modifying molecular mechanisms and are often associated with significant side effects. Bacopa monnieri, a traditional Indian herb with nootropic properties, has shown promise in neurological disorder treatment from ancient times. However, its mechanisms of action in Alzheimer's disease remain elusive. In this study, a cellular model for Alzheimer's disease was created by treating differentiated IMR-32 cells with beta-amyloid, 1–42 peptide (Aβ42). Additionally, a recovery model was established through co-treatment with Bacopa monnieri to explore its protective mechanism. Co-treatment with Bacopa monnieri extract recovered Aβ42 induced damage as evidenced by the decreased apoptosis and reduced reactive oxygen species production. Mass spectrometry-based quantitative proteomic analysis identified 21,674 peptides, corresponding to 3626 proteins from the Alzheimer's disease model. The proteins dysregulated by Aβ42 were implicated in cellular functions, such as negative regulation of cell proliferation and microtubule cytoskeleton organization. The enriched pathways include extracellular matrix organization and interleukin-4 and interleukin-13 signaling. Bacopa monnieri co-treatment showed remarkable restoration of Aβ42 altered proteins, including FOSL1, and TDO2. The protein-protein interaction network analysis of Bacopa monnieri restored proteins identified the hub gene involved in Alzheimer's disease. The findings from this study may open up new avenues for creating innovative therapeutic approaches for Alzheimer's disease.

Development of a dexamethasone-hyaluronic acid conjugate with selective targeting effect for acute lung injury therapy

Acute lung injury (ALI), a critical complication of COVID-19, is characterized by widespread inflammation and severe pulmonary damage, necessitating intensive care for those affected. Although glucocorticoids (GCs), such as dexamethasone (Dex), have been employed clinically to lower mortality, their nonspecific systemic distribution has led to significant side effects, limiting their use in ALI treatment. In this study, we explored the conjugation of Dex to hyaluronic acid (HA) to achieve targeted delivery to inflamed lung tissues. We achieved a conjugation efficiency exceeding 98 % using a cosolvent system, with subsequent ester bond cleavage releasing the active Dex, as verified by liquid chromatography. Biodistribution and cellular uptake studies indicated the potential of the HA conjugate for cluster of differentiation 44 (CD44)-mediated targeting and accumulation. In a lipopolysaccharide-induced ALI mouse model, intravenous (IV) HA-Dex administration showed superior anti-inflammatory effects compared to free Dex administration. Flow cytometry analysis suggested that the HA conjugate preferentially accumulated in lung macrophages, suggesting the possibility of reducing clinical Dex dosages through this targeted delivery approach.

The role and mechanism of dapagliflozin in Alzheimer disease: A review.

Alzheimer disease (AD), as the main type of dementia, is primarily characterized by cognitive dysfunction across multiple domains. Current drugs for AD have not achieved the desired clinical efficacy due to potential risks, inapplicability, high costs, significant side effects, and poor patient compliance. However, recent findings offer new hope by suggesting that sodium-glucose cotransporter 2 inhibitors (SGLT-2i) may possess neuroprotective properties, potentially opening up novel avenues for the treatment of AD. This review delves deeply into the multifaceted mechanisms of action of SGLT-2i in AD, encompassing antioxidative stress, antineuroinflammation, upregulation of autophagy, antiapoptosis, acetylcholinesterase inhibitor activity, and protection of endothelial cells against atherosclerosis and damage to the blood-brain barrier, among others. Furthermore, it provides an overview of recent advances in clinical research on this drug. These findings suggest that SGLT-2i is poised to emerge as a pivotal candidate for the treatment of AD, given its diverse functional effects.