A bioactive and biodegradable vitamin C stearate-based injectable hydrogel alleviates experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disorder affecting nearly 1% of the global population. In RA, synovial joints are infiltrated by inflammatory mediators and enzymes, leading to articular cartilage deterioration, joint damage, and bone erosion. Herein, the 9-aminoacridine-6-O-stearoyl-L-ascorbic acid hydrogel (9AA-SAA hydrogel) was formulated by the heat-cool method and further characterized for surface charge, surface morphology, rheology, and cytocompatibility. Furthermore, we evaluated the therapeutic efficacy of the 9AA-SAA hydrogel, an enzyme-responsive drug delivery system with on-and-off switching capabilities based on disease severity against collagen-induced experimental arthritis in Wistar rats. The anti-inflammatory action of the US FDA-approved drug 9-aminoacridine (9AA) was revealed which acted through nuclear receptor subfamily 4 group A member 1 (NR4A1), an anti-inflammatory orphan nuclear receptor that inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, we have explored the role of ascorbic acid, an active moiety of 6-O-stearoyl-L-ascorbic acid (SAA), in promoting the production of collagen production through ten-eleven translocation-2 (TET2) upregulation. Targeting through NR4A1 and TET2 could be the probable mechanism for the treatment of experimental arthritis. The combination of 9AA and ascorbic acid demonstrated enhanced therapeutic efficacy in the 9AA-SAA hydrogel, significantly reducing the severity of experimental arthritis. This approach, in contrast to existing treatments with limited effectiveness, presents a promising and more effective strategy for RA treatment by mitigating inflammation in experimental arthritis.

Analysing the Anticancer Properties of Pterostilbene Through Absorption, Distribution, Metabolism, and Excretion (ADME) and Molecular Docking Studies.

Aim The aim of this study is to examine the possible therapeutic effect of pterostilbene (PTS), a chemical present in grapes and blueberries, in the treatment of liver cancer by analysing its interactions with important proteins linked to the wingless/integrated (Wnt) signaling system. Objective Using computational techniques like molecular docking and absorption, distribution, metabolism, and excretion (ADME) studies, this research focuses on examining the pharmacokinetics and molecular interactions of PTS with proteins such as vimentin (Vim), glycogen synthase kinase 3 beta (GSK3-ß), epithelial cadherin (E-cadherin), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), c-Jun N-terminal kinase (JNK), and Wnt, all of which are connected to the Wnt signaling pathway in liver cancer. Methods The study includes the synthesis of proteins and ligands, ADME investigations for PTS, and AutoDock Vina molecular docking simulations to evaluate binding affinities and interactions. PTS is obtained from PubChem, while protein structures are obtained from the Protein Data Bank. Results Strong binding affinities between PTS and essential proteins in the Wnt signaling cascade are shown by molecular docking, which also highlights noteworthy hydrogen bonds, hydrophobic interactions, and electrostatic contacts. According to an ADME study, PTS has advantageous pharmacokinetic properties, such as moderate solubility, membrane permeability, and a minimal chance of drug interactions. Conclusion The extensive study highlights PTS's potential as a viable treatment option for liver cancer. The study promotes its investigation in cutting-edge liver cancer therapy approaches and urges more investigation into the molecular mechanisms, underpinning its anticancer properties. This paper sheds important light on the role of natural chemicals in cancer therapy and emphasizes the need for computational methods in drug discovery.

A chlorogenic acid-conjugated nanomicelle attenuates disease severity in experimental arthritis.

Rheumatoid arthritis (RA) is a systemic immune disorder marked by synovitis, bone damage, and cartilage erosion, leading to increased socio-economic burdens and reduced quality of life. Despite its unknown cause, advancements in understanding its pathophysiology have facilitated novel therapeutic approaches. Current treatments, including disease-modifying anti-rheumatic drugs (DMARDs) and biologics, often result in low efficacy and unnecessary side effects. To address the limitations of these drugs, carrier-based drug delivery systems, such as nanomicelles, have emerged as a promising solution. In this study, nanomicelles were synthesised utilizing PLGA (poly(lactic-co-glycolic acid)) as a backbone; this backbone is conjugated with chlorogenic acid (CGA), which is known for suppressing inflammation, and incorporates methotrexate (MTX), a model drug that is established for RA treatment. The nanomicelles were extensively characterized in terms of size, charge, drug loading, and drug-release behaviour. The in vivo assessment of MTX-PLGA-b-CGA nanomicelles in a collagen-induced arthritis model demonstrated a remarkable reduction in joint swelling, cartilage erosion, and disease severity. Furthermore, histological findings confirmed cartilage integrity and reduced expression of key pro-inflammatory markers, including receptor activator of nuclear factor kappa beta ligand (RANKL) and tumor necrosis factor (TNF-α). The approach based on the MTX-PLGA-b-CGA nanomicelles presents a biocompatible and potentially effective therapeutic strategy for management of the severity and progression of RA, providing a hopeful alternative for RA treatment.

Orthodontic treatment in adults: Challenges, outcomes, and factors affecting compliance and satisfaction.

BACKGROUND: The demand for orthodontic treatment among adults has witnessed a substantial rise in recent years. This study aims to explore the complexities of adult orthodontics, focusing on challenges faced, treatment outcomes, and the influence of factors such as age, gender, and education on patient compliance and satisfaction. METHODS: A multi-dimensional approach was employed, combining a review of clinical records with structured patient surveys. Descriptive statistics summarized demographic characteristics, treatment duration, and orthodontic problems addressed. Inferential statistics included Pearson correlation, Chi-squared tests, and analysis of variance to examine age compliance, gendersatisfaction, and education-orthodontic problem relationships. Qualitative analysis enriched findings, and statistical software facilitated data processing. RESULTS: The analysis revealed a statistically significant negative correlation between age and compliance (r = -0.28, P < 0.05), indicating that younger participants demonstrated higher compliance rates. Gender emerged as a significant factor influencing patient satisfaction (P = 0.024), with females reporting notably higher levels of satisfaction than males. Furthermore, participants with advanced education levels (Master's/Ph.D.) were significantly more likely to have orthodontic issues related to malocclusion (P = 0.041). CONCLUSION: The study provides an insight into the multi-dimensional aspects of adult orthodontics, recognizing the challenges, compliance, and satisfaction levels. Tailored approaches considering age, gender, and education are essential. This research contributes to a deeper understanding of orthodontic treatment in adults and its potential implications for enhanced patient care.

Sophorin mitigates flutamide-induced hepatotoxicity in wistar rats.

Flutamide is frequently used in the management of prostate cancer, hirsutism, and acne. It is a non-steroidal anti-androgenic drug and causes hepatotoxicity. The current study's objective is to evaluate sophorin's hepatoprotective effectiveness against flutamide-induced hepatotoxicity in Wistar rats. Sophorin is a citrus flavonoid glycoside, also known as rutin, which is a low molecular weight polyphenolic compound with natural antioxidant properties and reported to have promising hepatoprotective efficacy. In this study, sophorin was used at a dose of 100 mg/kg body weight in purified water via oral route for 4 week daily whereas, flutamide was used at a dose of 100 mg kg/b.wt for 4 weeks daily in 0.5% carboxy methyl cellulose (CMC) through the oral route for the induction of hepatotoxicity. Flutamide administration leads to enhanced reactive oxygen species (ROS) generation, an imbalance in redox homeostasis and peroxidation of lipid resulted in reduced natural antioxidant level in liver tissue. Our result demonstrated that sophorin significantly abrogate flutamide induced lipid peroxidation, protein carbonyl (PC), and also significantly increasesed in enzymatic activity/level of tissue natural antioxidant such as reduced glutathione(GSH), glutathione reductase(GR), catalase, and superoxide dismutase(SOD). Additionally, sophorin reduced the activity of cytochrome P450 3A1 in liver tissue which was elevated due to flutamide treatment. Furthermore, sophorin treatment significantly decreased the pro-inflammatory cytokines (TNF-α and IL-6) level. Immunohistochemical analysis for the expression of inflammatory proteins (iNOS and COX-2) in hepatic tissue was decreased after sophorin treatment against flutamide-induced hepatotoxicity. Moreover, sophorin suppressed the infiltration of mast cells in liver tissue which further showed anti-inflammatory potential of sophorin. Our histological investigation further demonstrated sophorin's hepatoprotective function by restoring the typical histology of the liver. Based on the aforementioned information, we are able to come to the conclusion that sophorin supplementation might benefit wistar rats with flutamide-induced hepatic damage by reducing oxidative stress and hepatocellular inflammation.

Spontaneous rupture of falciparum malarial spleen presenting as hemoperitoneum, hemothorax, and hemoarthrosis.

PATIENT: Male, 29 FINAL DIAGNOSIS: Spontaneous spleen rupture Symptoms: Abdominal distension • abdominal pain • abdominal tenderness • disorientation • fever • hemothorax • hip pain • reduced urine output MEDICATION: - Clinical Procedure: Splenectomy Specialty: Infectious Diseases. OBJECTIVE: Rare diseases. BACKGROUND: Spontaneous rupture of a malarial spleen is uncommon even in the endemic regions of malaria. This may lead to delayed or missed diagnosis of splenic rupture, which may be life threatening. CASE REPORT: We are reporting a patient with P. falciparum malaria who developed a spontaneous splenic rupture encountered in our department. A 29-year-old male patient with history of high grade intermittent fever with chills for 4 days followed by disorientation and reduced urine output and abdominal pain with distension associated with bilateral hip pain and dyspnea with bilateral chest pain (mainly on the left side) for 1 day. There was no history of any trauma or abnormal bleeding. Investigations revealed P. falciparum malaria, hemoperitoneum, hemothorax, and hemoarthrosis. Laparotomy confirmed hemoperitoneum with about 1.5 L of blood-stained fluid, enlarged friable spleen with rupture of the splenic capsule on the inner surface, and active bleeding. Splenectomy was performed. The patient was diagnosed with malarial spleen and received antimalarial therapy. CONCLUSIONS: Splenic rupture with hemoperitoneum should be managed with laparotomy and splenectomy, along with antimalarial drugs. A high index of suspicion is needed to detect these complications early.

Seasonal variations in cholinesterase activity, nerve conduction velocity and lung function among sprayers exposed to mixture of pesticides.

Pesticide spraying operation is associated with the increased risk of adverse health effects among sprayers who do not follow safe farm work practices. A study was conducted among pesticide sprayers in North India to evaluate the clinical and subclinical variations in their vital health parameters before and after the pesticide spraying season. Blood cholinesterase levels, pulmonary function test, nerve conduction velocity and self-reported symptoms were studied among 18 eligible and consenting male sprayers. Mean acetylcholinesterase activity was reduced by 55 % in the post-exposure assessment (P<0.001) as compared to pre-exposure levels. Mean forced expiratory volume in 1 s was 20 % lower in the post-exposure assessment as compared to the pre-exposure level (P<0.05). No significant change was observed in the motor and sensory nerve conduction velocity in the median nerve of sprayers before and after the spraying activity. Also, no significant variation was observed with respect to self-reported symptoms except weakness in arms and legs (P<0.05). The significant decline in lung function and acetylcholinesterase level after pesticide exposure reflects the strongly negative effect of exposure to pesticides during spraying activity. More longitudinal studies among pesticide sprayers must be undertaken to further substantiate the cause-effect relationship between pesticide exposure and its subclinical effects. There is a strong necessity to minimise the exposure through the use of personal protective equipment in pesticide sprayers.

Coronary artery disease.

Coronary artery disease (CAD) is the leading cause of death worldwide. There are several presenting clinical syndromes, including sudden cardiac death. Risk factor analysis can help the primary care provider identify patients who may need more extensive evaluation or treatment. Treatment may be medical or surgical and depends on the individual patient's comorbidities and preferences. In the future, growth of new blood vessels or cardiac cells may aid in the treatment of CAD.

Adverse health effects of pesticides in agrarian populations of developing countries.

Developing countries use only 20% of the world's agrochemicals, yet they suffer 99% of deaths from pesticide poisoning. Pesticide poisoning is a significant problem in developing countries primarily because of unsafe pesticide application and handling practices. Safety is further exacerbated by the illiteracy and poverty that prevails in most farming communities of developing countries. Pesticides classified as being extremely or highly hazardous by FAO and WHO, including those banned by other countries, continue to be used in developing countries. Many farmers in developing countries continue to be exposed to pesticides from either storing them in or near their residences, or from inadequate or unsafe application or handling practices. Farming populations exposed to pesticides suffer from several health problems, primarily neurological abnormalities, respiratory ailments, and reproductive, endocrinological, and dermal problems. In developing countries, the scientific literature (including the Indian Institute of Toxicology Research, India) have taken the initiative to monitor health problems resulting from pesticide exposure in agrarian communities. The welfare fund for agricultural laborers could institute a special program for pesticide applicators in developing countries. The primary need, currently, in such countries is creation and implementation of sound national policies to effectively articulate appropriate guidelines for managing farm pest control activities. Such policies should be aimed at both limiting pesticide exposure and usage, but doing so without damaging the yields of food production. If such steps are taken, it is fully expected that the incidence of adverse health consequences for agrarian populations from pesticide toxicity will decrease, and the health of farmers improve.