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Obesity is a known risk factor for many chronic diseases and a substantial threat to public health. We investigated the effects of figs sourced from Ficus hispida on a high fat-fed experimental rat model. We found that a 500-mg dose of ethanolic extract of figs (EFH) reduced oxidative stress markers nitric oxide (NO), malondialdehyde (MDA), and advanced oxidation protein products (AOPP), which were increased in high fat-fed rats. Antioxidant enzymes superoxide dismutase (SOD), catalase, reduced glutathione (GSH), and myeloperoxidase (MPO), found elevated in high fat-fed rats, were also normalized to nearly regular levels by fig treatment. Administration of EFH further reduced fat deposition and expression of adipogenic genes leptin, fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein-1c (SERBP-1c). Our results suggest that figs have significant effects on reducing oxidative stress and mitigating obesity-associated liver and adipose tissue abnormalities via suppressing adipogenesis. Thus, we propose that F. hispida has potential benefits in reducing obesity.
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Subcutaneous (SC) administration of chemotherapeutics combined with near-infrared (NIR) light activation can effectively target skin tumors by triggering localized drug release and enhancing cytotoxic effects. In this study, we developed NIR-responsive indocyanine green (ICG) and the chemotherapeutic agent doxorubicin (Dox) loaded into gelatin nanoparticles (NPs) for SC delivery in a skin tumor-bearing mouse model. Histological examination (hematoxylin and eosin staining) confirmed the successful delivery and swelling behavior of the Dox/ICG-loaded gelatin NPs at the SC site. In vitro and in vivo experiments demonstrated that NIR activation of the Dox/ICG-loaded gelatin NPs generated significant photothermal heat (48 and 46 °C), leading to targeted drug release and a substantial reduction in skin tumor size (from 15 to 3 mm3). Our findings suggest that this dual-modality approach of SC chemotherapeutic administration and NIR-triggered photothermal therapy can concentrate cytotoxic drugs at the tumor site, offering a promising strategy for improving skin cancer treatment.
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Prostacyclin or prostaglandin I2 (PGI2), a metabolite of arachidonic cyclooxygenase pathway, has been demonstrated as an effector of adipocyte differentiation. However, due to its instability in biological fluid, it is difficult to evaluate the role of PGI2 in regulating adipocyte differentiation in different stages in culture. Therefore, this study aimed to establish a simple and rapid method for the production of monoclonal antibody against 6-Keto PGF1α, a stable PGI2 metabolite, and its quantification to determine the role of PGI2 in culture medium. Eight-week-old female BALB/c mice were immunized with the hapten of 6-Keto PGF1α and BSA for several weeks until a higher antibody titer (absorbance value > 0.9 at 1000-times dilution) against 6-Keto PGF1α was found. Then, fusion of antibody-producing spleen lymphocytes with SP-2 myeloma cells and thymocytes was performed and cultured in HAT-medium supplemented with hypoxanthine, aminopterin, and thymine. Specific antibody-producing cells (M2-A4-B8-D10) against 6-Keto PGF1α were identified and separated. A standard ELISA calibration curve was developed with 100% reactivity for 6-Keto-PGF 1 α ranging from 0.26 pg to 6.44 ng corresponding to 90% and 10% of the maximum binding capacity for the immobilized antigen respectively. This method can easily be applied to monitor PGI2 regulation in different stages of cultured adipocytes to reveal the regulatory roles of PGI2 in maintaining homeostasis and adipocyte differentiation.
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We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of â¼20 nm are tracked under the vein visualization imaging system in the presence of loaded paclitaxel and NIR-active agents. The ability to track liposome nanocarriers is recorded on the tissue-mimicking phantom model and in vivo mouse veins after intravenous administration. The trackable liposome delivery provides in vitro and in vivo photothermal heat (â¼40 °C) for NIR-light-triggered area-specific chemotherapeutic release. This approach can be linked with a real-time vein-imaging system to track and apply area-specific local heat, which hitchhikes liposomes from the vein and finally releases them at the tumor site. We conducted studies on mice skin tumors that indicated the disappearance of tumors visibly and histologically (H&E stains). The ability of nanocarriers to monitor after administration is crucial for improving the effectiveness and specificity of cancer therapy, which could be achieved in the trackable delivery system.
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Raios Infravermelhos , Lipossomos , Paclitaxel , Medicina de Precisão , Neoplasias Cutâneas , Lipossomos/química , Animais , Camundongos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/terapia , Paclitaxel/química , Paclitaxel/administração & dosagem , Paclitaxel/farmacologia , Teste de Materiais , Materiais Biocompatíveis/química , Tamanho da Partícula , Humanos , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
This study focused to assess the efficacy of Gynura procumbens (GP) leaf extract against cisplatin (CP)-induced hepatorenal complications in Wister albino rats. Additionally, it aims to detect polyphenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD). The rats were treated intraperitoneally with CP (7.5â mg/kg) to mediate hepatorenal damage. They were then treated with GP extract (75 and 150â mg/kg, P.O.) for 7 consecutive days. Although GP extract significantly ameliorated CP-mediated hepatorenal biomarkers like alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) levels in a dose-dependent manner, GP extract at 150â mg/kg dose normalized hepatorenal biomarkers ALP (45.11â U/L), ALT (34â U/L), AST (29â U/L), creatinine (10.3â mg/dl) and BUN (11.19â mg/dl) while comparing to control and disease group. Similarly, though it significantly reduced CP-induced oxidative stress inducers, including nitric oxide (NO) and advanced oxidative protein products (AOPP), higher dose (150â mg/kg) exhibited better activity in reducing NO (281.54â mmol/gm tissue in liver and 52.73â mmol/gm tissue in the kidney) and AOPP (770.95â mmol/mg protein in liver and 651.90â mmol/mg protein in the kidney). Besides, it showed better enhancement in the antioxidant enzymes superoxide dismutase, and glutathione levels at a higher dose (150â mg/kg). Histopathological studies showed that CP caused collagen accumulation in the liver and kidney tissues. GP extract drained the collagen mass and acted against hepatorenal damage. Ellagic acid, gallic acid, quercetin hydrate, kaempferol, and rutin hydrate were revealed in GP extract. In-silico modelling showed good docking scores of the polyphenolic compounds with molecular targets including CYP4502E1, NF-κB, caspase-3, and TNF-α. GP could be an effective therapeutic option for management of anticancer drugs' complications like CP-induced organ damage, although clinical studies are required to establish herbal formulation.
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Cisplatino , Estresse Oxidativo , Extratos Vegetais , Ratos Wistar , Animais , Estresse Oxidativo/efeitos dos fármacos , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Masculino , Folhas de Planta/química , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Asteraceae/química , Antioxidantes/farmacologia , Antioxidantes/química , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Simulação de Acoplamento Molecular , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Antineoplásicos/farmacologia , Antineoplásicos/químicaRESUMO
Background: Global prevalence of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease is increasing gradually, whereas approvals of successful therapeutics for central nervous system disorders are inadequate. Accumulating evidence suggests pivotal roles of the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in modulating neuroinflammation and necroptosis. Discoveries of potent small molecule inhibitors for RIPK1 with favorable pharmacokinetic properties could thus address the unmet medical needs in treating neurodegeneration. Methods: In a structure-based virtual screening, we performed site-specific molecular docking of 4,858 flavonoids against the kinase domain of RIPK1 using AutoDock Vina. We predicted physicochemical descriptors of the top ligands using the SwissADME webserver. Binding interactions of the best ligands and the reference ligand L8D were validated using replicated 500-ns Gromacs molecular dynamics simulations and free energy calculations. Results: From Vina docking, we shortlisted the top 20 flavonoids with the highest binding affinities, ranging from -11.7 to -10.6 kcal/mol. Pharmacokinetic profiling narrowed down the list to three orally bioavailable and blood-brain-barrier penetrant flavonoids: Nitiducarpin, Pinocembrin 7-O-benzoate, and Paratocarpin J. Next, trajectories of molecular dynamics simulations of the top protein-ligand complexes were analyzed for binding interactions. The root-mean-square deviation (RMSD) was 1.191 Å (±0.498 Å), 1.725 Å (±0.828 Å), 1.923 Å (±0.942 Å), 0.972 Å (±0.155 Å) for Nitiducarpin, Pinocembrin 7-O-benzoate, Paratocarpin J, and L8D, respectively. The radius of gyration (Rg) was 2.034 nm (±0.015 nm), 2.0.39 nm (± 0.025 nm), 2.053 nm (±0.021 nm), 2.037 nm (±0.016 nm) for Nitiducarpin, Pinocembrin 7-O-benzoate, Paratocarpin J, and L8D, respectively. The solvent accessible surface area (SASA) was 159.477 nm2 (±3.021 nm2), 159.661 nm2 (± 3.707 nm2), 160.755 nm2 (±4.252 nm2), 156.630 nm2 (±3.521 nm2), for Nitiducarpin, Pinocembrin 7-O-benzoate, Paratocarpin J, and L8D complexes, respectively. Therefore, lower RMSD, Rg, and SASA values demonstrated that Nitiducarpin formed the most stable complex with the target protein among the best three ligands. Finally, 2D protein-ligand interaction analysis revealed persistent hydrophobic interactions of Nitiducarpin with the critical residues of RIPK1, including the catalytic triads and the activation loop residues, implicated in the kinase activity and ligand binding. Conclusion: Our target-based virtual screening identified three flavonoids as strong RIPK1 inhibitors, with Nitiducarpin exhibiting the most potent inhibitory potential. Future in vitro and in vivo studies with these ligands could offer new hope for developing effective therapeutics and improving the quality of life for individuals affected by neurodegeneration.
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Flavonoides , Qualidade de Vida , Humanos , Simulação de Acoplamento Molecular , Flavonoides/farmacologia , Ligantes , Benzoatos , Proteína Serina-Treonina Quinases de Interação com ReceptoresRESUMO
Polymorphisms of the disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) are linked to pathophysiological changes in lung inflammation, cancer, Alzheimer's disease (AD), encephalopathy, liver fibrosis, and cardiovascular diseases. In this study, we predicted the pathogenicity of ADAM10 non-synonymous single nucleotide polymorphisms (nsSNPs) in a wide array of mutation analyzing bioinformatics tools. We retrieved 423 nsSNPs from dbSNP-NCBI for the analysis, and 13 were predicted deleterious by each of the ten tools: SIFT, PROVEAN, CONDEL, PANTHER-PSEP, SNAP2, SuSPect, PolyPhen-2, Meta-SNP, Mutation Assessor and Predict-SNP. Further assessment of amino acid sequences, homology models, conservation profiles, and inter-atomic interactions identified C222G, G361E and C639Y as the most pathogenic mutations. We validated this prediction through structural stability analysis using DUET, I-Mutant Suite, SNPeffect and Dynamut. Molecular dynamics simulations and principal component analysis also indicated considerable instability of the C222G, G361E and C639Y variants. Therefore, these ADAM10 nsSNPs could be candidates for diagnostic genetic screening and therapeutic molecular targeting.Communicated by Ramaswamy H. Sarma.
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Simulação de Dinâmica Molecular , Polimorfismo de Nucleotídeo Único , Mutação , Sequência de Aminoácidos , Biologia Computacional/métodosRESUMO
Lung cancer is responsible for causing one of the highest numbers of cancer deaths. In Bangladesh, both men and women are affected by lung cancer, and environmental contaminants are believed to be one of the main risk factors apart from smoking. The diagnosis of lung cancer is difficult due to the delicate structure and complexity of the lungs. Diagnosis in later stages results in a poor prognosis of the disease. Tissue biopsy is the most reliable way of identifying lung cancer, but it is invasive and requires identification of the primary neoplasm within the lungs. As inflammation is involved in carcinogenesis, circulating levels of cytokines might be elevated in patients during the early stages of cancer. Increased IL-6 levels have been associated with the promotion of tumor growth, and IL-17 is believed to aid metastasis of lung cancer. In this study, the use of IL-6 and IL-17 was investigated as diagnostic markers for lung cancer. IL-6 and IL-17 levels were compared between 35 lung cancer patients and 19 healthy individuals. IL-6 levels were markedly elevated (7.417 pg/mL) in lung cancer cases compared to the controls (0.970 pg/mL), indicating a positive correlation (p < 0.05). IL-17 levels were only slightly higher in lung cancer patients (9.400 pg/mL) compared to healthy individuals (8.922 pg/mL). Both IL-6 and IL-17 levels were higher in patients with adenocarcinoma compared with other subtypes of lung cancer. Treatment with chemotherapy and radiotherapy did not significantly affect IL-6 levels. However, IL-17 levels were reduced due to cancer treatment. Further studies with larger sample sizes assessing the IL-6 and IL-17 in lung cancer patients are needed to establish the diagnostic role of the two cytokines.
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Previously, we observed curcumin improves aging-associated memory impairment in D-galactose (D-gal) and normal-aged (NA) mice. Evidence showed that multiple agents can be used in managing aging-induced memory dysfunction, drawn by the contribution of several pathways. Curcumin and Epigallocatechin 3 gallate (EGCG) combination substantially reduced the oxidative stress that commonly mediates aging. This study examined the combined effect of EGCG and curcumin on memory improvement in two recognized models, D-gal and normal-aged (NA) mice. The co-administration of EGCG and curcumin significantly (p < 0.05) increased retention time detected by passive avoidance (PA) and freezing response determined in contextual fear conditioning (CFC) compared to the discrete administration of EGCG or curcumin. Biochemical studies revealed that the combination of EGCG and curcumin remarkably ameliorated the levels (p < 0.05) of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation compared to the monotherapy of EGCG or curcumin in mice hippocampi. The behavioral and biochemical studies revealed that the combination of EGCG and curcumin showed better improvement in rescuing aging-associated memory disorders in mice. EGCG and curcumin combination could serve as a better choice in managing aging-related memory disorders.
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Catequina , Curcumina , Camundongos , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Galactose/farmacologia , Envelhecimento/fisiologia , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/induzido quimicamente , Estresse OxidativoRESUMO
Antibiotic resistance has been recognized as a public health threat in recent years, and mortality due to resistance is increasing alarmingly every year. Antibiotic resistance, among many factors, may arise due to the consumption of substandard antibiotic brands that provide subnormal levels of the drug in the blood. Post-market evaluation can provide important information in assessing pharmaceutical products in terms of quality, purity, and therapeutic aspects. Ciprofloxacin, a broad-spectrum antibiotic, has been used against a wide range of infectious diseases in Bangladesh. The present study aimed to determine the quality attributes of twenty-two commonly prescribed brands of ciprofloxacin 500 mg tablet collected from Dhaka city and the rural regions of Jessore. RP-HPLC coupled with UV-visible spectrophotometry was used to determine the potency of ciprofloxacin in tablets, and the zone of inhibition was determined using Kirby-Bauer's disc diffusion method to assess the antimicrobial efficacy against different strains of microorganisms. We found that 95.45% of brands (21 out of 22 brands) of ciprofloxacin tablets met United States Pharmacopoeia (USP) and British Pharmacopoeia (BP) specified potency, whereas one brand failed. From dissolution studies, we observed that 68.2% of brands (15 out of 22 brands) followed USP/NF dissolution test specifications, whereas 31.8% (7 out of 22 brands) failed to release 80% of the labeled amount of drug within 30 min. Drug release kinetics data showed that most brands followed the Weibull drug release kinetic model. Fit factor analysis exhibited that 8 brands out of 22 (36.4%) failed to comply similar dissolution profiles with the reference product. Minimum inhibitory concentrations, assessed against five bacterial strains, further showed good antimicrobial sensitivity by all brands.
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Liver disease is a serious health problem affecting people worldwide at an alarming rate. The present study aimed to investigate the protective effects of Ganoderma lucidum against CCl4-induced liver toxicity in rats. The experimental Long Evans rats were divided into five groups, of which four groups were treated with carbon tetrachloride (CCl4). Among the CCl4 treated groups, one of the groups was treated with silymarin and two of them with ethanolic extract of G. lucidum at 100 and 200 mg/Kg body weight. The oxidative stress parameters and endogenous antioxidant enzyme concentrations were assessed by biochemical tests. Liver enzymes ALT, AST, and ALP were determined spectrophotometrically. Histopathological examinations were carried out to assess hepatic tissue damage and fibrosis. Reverse transcription PCR (RT-PCR) was performed to determine the expression of IL-1ß, IL-6, IL-10, TNF-α, and TGF-ß genes. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis revealed that G. lucidum is rich in several phytochemicals including 6-Octadecanoic acid (55.81%), l-( +)-Ascorbic acid 2,6-dihexadecanoate (18.72%), Cis-11-Eicosenamide (5.76%), and Octadecanoic acid (5.26%). Treatment with the G. lucidum extract reduced the elevated ALT, AST, ALP levels, and cellular oxidative stress markers and increased the endogenous antioxidant levels. Histopathology observations revealed that the inflammation, infiltration of immune cells, and aberration of collagen fibers in the hepatocytes were altered by the G. lucidum treatment. The increased expression of inflammatory cytokines TNF-α, TGF-ß, IL-1 ß, and IL-6 were markedly suppressed by G. lucidum extract treatment. G. lucidum also prevented the suppression of protective IL-10 expression by CCl4. This study strongly suggests that G. lucidum extract possesses significant hepatoprotective activity as evidenced by reduced oxidative stress and inflammation mediated by suppression in inflammatory cytokine expression and increased protective IL-10 cytokine expression.
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Doença Hepática Induzida por Substâncias e Drogas , Reishi , Ratos , Animais , Antioxidantes/metabolismo , Fígado/metabolismo , Ratos Long-Evans , Reishi/metabolismo , Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Estresse Oxidativo , Inflamação/patologia , Extratos Vegetais/farmacologia , Citocinas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Tetracloreto de Carbono/toxicidadeRESUMO
INTRODUCTION: Inappropriate antibiotic use in community settings significantly contributes to antimicrobial resistance (AMR) globally, compromising the quality of life and threatening public health. This study aimed to identify AMR contributing factors by analyzing the knowledge, attitude, and practice (KAP) of the unqualified village medical practitioners and pharmacy shopkeepers in rural Bangladesh. METHODS: We performed a cross-sectional study where the participants were pharmacy shopkeepers and unqualified village medical practitioners aged ≥ 18 years and living in Sylhet and Jashore districts in Bangladesh. Primary outcome variables were knowledge, attitude, and practice of antibiotic use and AMR. RESULTS: Among the 396 participants, all were male aged between 18 and 70 years, 247 were unqualified village medical practitioners, and 149 were pharmacy shopkeepers, and the response rate was 79%. Participants showed moderate to poor knowledge (unqualified village medical practitioners, 62.59%; pharmacy shopkeepers, 54.73%), positive to neutral attitude (unqualified village medical practitioners, 80.37%, pharmacy shopkeepers, 75.30%), and moderate practice (unqualified village medical practitioners, 71.44%; pharmacy shopkeepers, 68.65%) scores regarding antibiotic use and AMR. The KAP score range was 40.95-87.62%, and the mean score was statistically significantly higher for unqualified village medical practitioners than pharmacy shopkeepers. Multiple linear regression analysis suggested that having a bachelor's degree, pharmacy training, and medical training were associated with higher KAP scores. CONCLUSION: Our survey results demonstrated that unqualified village medical practitioners and pharmacy shopkeepers in Bangladesh possess moderate to poor knowledge and practice scores on antibiotic use and AMR. Therefore, awareness campaigns and training programs targeting unqualified village medical practitioners and pharmacy shopkeepers should be prioritized, antibiotic sales by pharmacy shopkeepers without prescriptions should be strictly monitored, and relevant national policies should be updated and implemented.
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Antibacterianos , Farmácia , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Antibacterianos/uso terapêutico , Estudos Transversais , Bangladesh , Conhecimentos, Atitudes e Prática em Saúde , Qualidade de Vida , Farmacorresistência BacterianaRESUMO
Background and Aims: Cervical cancer is characterized by abnormal cell growth in the lining of cervix and it is the second major cause of cancer-related deaths among females in Bangladesh. Interleukin-6 (IL-6) is a multifunctional cytokine that has been heavily linked with cervical cancer. Our aim was to investigate the association of two promoter single-nucleotide polymorphisms (SNPs) of IL-6 (rs1800795 and rs1800797) with the susceptibility of cervical cancer in Bangladeshi women. Methods: DNA was extracted from venous blood samples from cervical cancer patients (n = 126) and healthy controls (n = 120). Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping of the selected SNPs. Logistic regression was performed to calculate the odds ratio (OR) with 95% confidence interval (CI) and p values. Results: We found a significant association between rs1800795 and rs1800797 polymorphisms and cervical cancer. For, rs1800795 (G > C) the GC heterozygous genotype (OR = 2.80, 95% CI = 1.55-5.07, p = 0.0007) and CC mutant homozygous genotype (OR = 3.5, 95% CI = 1.29-9.51, p = 0.014) conferred an increased risk of cervical cancer. In case of rs1800797 (G > A) polymorphism, the AG heterozygous genotype (OR = 6.94, 95% CI = 3.76-12.81, p < 0.0001) and AA mutant homozygous genotype (OR = 3.88, 95% CI = 1.12-13.51, p = 0.0332) also exhibited an elevated risk of cervical cancer. Use of contraceptives was found as risk factor and patients who smoke were carriers of both the risk alleles and thus had an increased risk of cervical cancer. Conclusion: Our findings suggest that polymorphism of rs1800795 and rs1800797 of the IL-6 gene play a significant role in cervical cancer susceptibility in Bangladeshi women.
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We describe the synthesis of a nanostructured dermal patch composed of chitosan-tannic acid (CT) that can carry near-infrared (NIR) active Indocyanine green (ICG) dye for performing photothermal heat conversion activity. The NIR-responsive CT-I dermal patch can deliver topical antibiotic drugs (Neomycin). The CT-I and drug-loaded CT-I/N patches have been demonstrated by FTIR, SEM/EDX, TGA, and DSC analysis. The in vitro drug release from the CT-I/N patch are favorable in the dermal environment (pH = 5.5) and significantly increases 25 % more at higher temperatures of 40 to 45 °C. The CT-I/N showed increasing photothermal heat in response to NIR (808 nm) light. The in vivo thermograph demonstrated that the CT-I/N patch can generate >45 °C within 5 min NIR irradiation. As a result, sustained wound healing was shown in H&E (hematoxylin and eosin) staining dermal tissue. Such NIR-active nanostructure film/patch is promising for the future of any sustained on-demand drug delivery system.
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Quitosana , Nanoestruturas , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Temperatura Alta , Liberação Controlada de FármacosRESUMO
Carbofuran is a widely used poisonous pesticide around the world that helps to control insects during farming. Upon oral ingestion to humans, it exaggerates oxidative stress in various organs like the liver, brain, kidney, and heart. Several studies reported that oxidative stress in the liver initiates and propagates hepatic cell necrosis, ultimately resulting in hepatotoxicity. It also reported that coenzyme Q10 (CoQ10) can neutralize oxidative stress due to its antioxidant properties. However, the hepatoprotective and nephroprotective role of CoQ10 against carbofuran toxicity has not been investigated. Therefore, the present study aimed to evaluate the hepatoprotective and nephroprotective role of CoQ10 in carbofuran-induced hepatotoxicity and nephrotoxicity in a mouse model for the first time. We determined the blood serum diagnostic markers, oxidative stress parameters, antioxidant system, and histopathological characteristics of liver and kidney tissues. The administration of 100 mg/kg of CoQ10 in carbofuran-treated rats significantly attenuated AST, ALT, ALP, serum creatinine, and BUN levels. Moreover, CoQ10 (100 mg/kg) remarkably altered the level of NO, MDA, AOPP, GSH, SOD, and CAT in both the liver and kidney. The histopathological data also unveiled that CoQ10 treatment prevented inflammatory cell infiltration in carbofuran-exposed rats. Therefore, our findings infer that CoQ10 may effectively protect liver and kidney tissues against carbofuran-induced oxidative hepatotoxicity and nephrotoxicity.
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Background: Urinary tract infection (UTI) is one of the most recurrent infections in the community and healthcare settings. Although many studies related with microbial sensitivity (MS) of uropathogens (UPs) to antibiotics have been done in Bangladesh, no conclusive study has compared antibiotic sensitivity (AS) to UPs in diabetic and non-diabetic patients. The aim of the study is to find out whether there is a difference in AS in common UPs between diabetic and non-diabetic UTI patients. Methods: A retrospective review was conducted on 833 patients. The data was collected from different diagnostic centers located within Dhaka city in Bangladesh, and the data was analyzed using convenient statistical tools. Results: We have studied a total of 833 UTI patients. Out of 833 patients, 664 were diabetic and 169 were non-diabetic patients respectively. Among the studied population, females were found to be more inclined to have UTIs as compared to males. E. coli was found to be the leading UPs in our study. Patients within the age of 20-34 were more vulnerable to UTI in both groups. Imipenem and meropenem showed 100% sensitivity against E. coli, Staphylococcus and Klebsiella in non-diabetic patients, while both antibiotics showed lower sensitivity to the same organisms in diabetic patients. Antibiotics like nitrofurantoin (p ≤ 0.0002), ceftazidime (p ≤ 0.0124) and ceftriaxone (p ≤ 0.0168) showed less sensitivity to E. coli in diabetic UTI patients as compared to non-diabetic UTI patients. Overall sensitivity patterns elucidated that all the studied antibiotics, except ciprofloxacin and levofloxacin, showed lower sensitivity against UPs in diabetic while compared to non-diabetic UTI patients (p= <0.05 to 0.0001). Conclusion: We found significant difference in microbial sensitivity in patients with diabetes compared to non-diabetic UTI patients. Diabetes changes the pathophysiological state of the uropathogens leading to the declining sensitivity of the antibiotics in diabetic patients with UTIs.
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The human receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a critical necroptosis regulator implicated in cancer, psoriasis, ulcerative colitis, rheumatoid arthritis, Alzheimer's disease, and multiple sclerosis. Currently, there are no specific RIPK1 antagonists in clinical practice. In this study, we took a target-based computational approach to identify blood-brain-barrier-permeable potent RIPK1 ligands with novel chemotypes. Using molecular docking, we virtually screened the Marine Natural Products (MNP) library of 14,492 small molecules. Initial 18 hits were subjected to detailed ADMET profiling for bioavailability, brain penetration, druglikeness, and toxicities and eventually yielded 548773-66-6 as the best ligand. RIPK1 548773-66-6 binding was validated through duplicated molecular dynamics (MD) simulations where the co-crystallized ligand L8D served as a reference. Trajectory analysis indicated negligible Root-Mean-Square-Deviations (RMSDs) of the best ligand 548773-66-6 relative to the protein backbone: 0.156 ± 0.043 nm and 0.296 ± 0.044 nm (mean ± standard deviations) in two individual simulations. Visual inspection confirmed that 548773-66-6 occupied the RIPK1 ligand-binding pocket associated with the kinase activation loop. Further computations demonstrated consistent hydrogen bond interactions of the ligand with the residue ASP156. Binding free energy estimation also supported stable interactions of 548773-66-6 and RIPK1. Together, our in silico analysis predicted 548773-66-6 as a novel ligand for RIPK1. Therefore, 548773-66-6 could be a viable lead for inhibiting necroptosis in central nervous system inflammatory disorders.Communicated by Ramaswamy H. Sarma.
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BACKGROUND: Much scholarly debate has centered on Bangladesh's family planning program (FPP) in lowering the country's fertility rate. This study aimed to investigate the prevalence of using modern and traditional contraceptive methods and to determine the factors that explain the contraceptive methods use. METHODS: The study used data from the 2017-18 Bangladesh Demographic and Health Survey (BDHS), which included 11,452 (weighted) women aged 15-49 years in the analysis. Multilevel multinomial logistic regression was used to identify the factors associated with the contraceptive method use. RESULTS: The prevalence of using modern contraceptive methods was 72.16%, while 14.58% of women used traditional methods in Bangladesh. In comparison to women in the 15-24 years age group, older women (35-49 years) were more unwilling to use modern contraceptive methods (RRR: 0.28, 95% CI: 0.21-0.37). Women who had at least a living child were more likely to use both traditional and modern contraceptive methods (RRR: 4.37, 95% CI: 3.12-6.11). Similarly, given birth in the previous 5 years influenced women 2.41 times more to use modern method compared to those who had not given birth (RRR: 2.41, 95% CI: 1.65-3.52). Husbands'/partners' decision for using/not using contraception were positively associated with the use of both traditional (RRR: 4.49, 95% CI: 3.04-6.63) and modern methods (RRR: 3.01, 95% CI: 2.15-4.17) rather than using no method. This study suggests rural participants were 21% less likely to utilize modern methods than urban participants (RRR: 0.79, 95% CI: 0.67-0.94). CONCLUSION: Bangladesh remains a focus for contraceptive use, as it is one of the most populous countries in South Asia. To lower the fertility rate, policymakers may design interventions to improve awareness especially targeting uneducated, and rural reproductive women in Bangladesh. The study also highlights the importance of male partners' decision-making regarding women's contraceptive use.