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1.
Indian J Surg Oncol ; 15(Suppl 3): 461-464, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39328725

RESUMO

A primitive neuroectodermal tumor (PNET), classified as a malignancy of the Ewing's sarcoma family of tumors, is typically observed in bones or soft tissue among adolescents and young adults. However, its occurrence outside the skeletal system (extra-osseous location), particularly within visceral organs, is infrequent. Renal PNET is exceptionally uncommon and exhibits an exceedingly aggressive biological behavior, leading to a dismal prognosis as compared to conventional renal cell carcinoma. In this report, we present the case of a 28-year-old adult male patient diagnosed with renal PNET on ultrasound-guided biopsy, who initially presented with left flank pain and recent onset of hematuria within a brief timeframe. Left radical nephrectomy followed by postoperative VDC-IE (combined vincristine, doxorubicin, and cyclophosphamide followed by another combination of ifosfamide and etoposide) chemotherapy was given to the patient. This case serves as a reminder to nephrologists, medical oncologists, and pathologists that in adolescents and young adults presenting with suspicious renal masses, a diagnosis of renal PNET should always be considered. Timely surgical intervention, coupled with chemotherapy, is essential for optimal therapeutic management and improved prognosis in cases of such rare and aggressive malignancies.

2.
Chem Biodivers ; : e202401810, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225328

RESUMO

In the present study, a new series of 1,2,4‒triazole linked pyrazole hybrids (5a‒5l) were synthesized from dimethyl amino pyrazole (1) in good yield by three-step reaction. The chemical structures of the resulted compounds were thoroughly elucidated using spectral analyses such as IR, 1H-NMR, 13C-NMR, mass spectra and elemental analysis. The target compounds were screened for their antimicrobial activities against the various standard pathogen strains, Gram‒(‒ve) (E. coli, P. aeruginosa, K. pneumoniae, A. baumannii), and Gram‒(+ve) (S. aureus,S. faecalis) microorganisms. According to the results obtained, in particular, compounds 5b, 5f, 5h and 5j was effective at inhibiting the antibacterial growth of all the bacteria's, having MIC values ranging 0.983‒14.862 mg/mL and compared to moxifloxacin (1.391‒22.01 mg mL-1). The most active compounds were chosen to interact with the DNA gyrase and topoisomerase-IV targets via molecular docking. These selected ligands interacted with PDB targets 2XCO, 1S16 and docked into the active site of amino acids Ala-269, Gly-413, Asn-405, Ser-1182, Thr-1185, His-1186, His-1186, Lys-1189, and Trp-1213. The pharmacokinetic properties, stability, and drug-likeness parameters of all target molecules were estimated using SwissADME and PkCSM protocols. The current study used in silico approaches combining e-pharmacophore modeling and structure-based molecular docking of targets to identify antimicrobial agents.

3.
Food Chem ; 463(Pt 1): 141031, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39236381

RESUMO

Ficus auriculata Lour. (Moraceae) is an underutilized wild edible fruit widely consumed for its nutritional properties. The present study aimed to determine the phytochemical composition and in vitro antioxidant, enzyme inhibitory, anti-inflammatory and anti-cancerous properties of the F. auriculata fruit extracts through in vitro digestion (oral, gastric and intestinal phases). The extracts were obtained by hot extraction and cold maceration methods using aqueous and methanolic solvents. Major phytoconstituents identified through LC-MS was subjected to molecular docking against the target proteins. The elemental analysis shows the presence of major elements; high levels of total phenolics (124.61 ± 0.82 mg gallic acid equivalent/g), flavonoids (76.38 ± 0.82 mg quercetin equivalent/g), vitamin E (32.48 ± 0.09 mg alpha-tocopherol equivalent/g), and carbohydrate (34.59 ± 0.45 mg glucose equivalent/g) in hot extracted methanolic undigested extract (HEM UD) and high level of total protein (124.71 ± 0.34 mg bovine serum albumin equivalent/g) in cold extracted methanolic undigested fruit extract were found. HEM UD showed high antioxidant activity in 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), 2,2-diphenyl-1-picryl-hydrazyl, and superoxide radical scavenging assays with IC50 of 53.30 ± 0.57, 80.69 ± 0.12, and 65.47 ± 1.13 µg/mL, respectively. The HEM UD extract also potentially inhibited the enzyme activity of α-amylase, α-glucosidase, tyrosinase, and protein denaturation (IC50 of 67.76 ± 1.22, 83.18 ± 1.23, 87.24 ± 1.15, and 65.76 ± 0.60 µg/mL). The most potent extract (HEM UD) was studied for its anticancer effects by MTT assay against the MCF-7 and HeLa cell lines and showed the IC50 of 89.80 ± 0.56 and 60.76 ± 0.04 µg/mL, respectively. The LC-MS analysis elucidated ten phytoconstituents. Based on the molecular docking study, querciturone could potentially be an effective constituent in treating diabetes and inflammation-related issues. The findings indicated the ability of F. auriculata fruits as a promising functional food.

4.
Reprod Toxicol ; 130: 108724, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39322090

RESUMO

Bisphenol A (BPA) belongs to the endocrine disruptor chemicals (EDCs) causing various reproductive disorders in females. We analysed the toxic effects of BPA in the uterus and ovaries. The BPA was administered orally with the repeated low dose (LD, 1 mg/kg) and high dose (HD, 5 mg/kg) of body weight on alternate days for 4 months via oral gavage to Swiss mice. BPA administration decreases body weight, ovarian weight and size at LD, but increases ovarian weight and size at HD. The uterus weight, length, and diameter were increased in both the treated groups. The histopathological data show decreased ovarian follicle size, epithelial hyperplasia, and lymphocytic infiltration in the ovary. The BPA-treated uterus shows increased vascularization, atrophied endometrium and myometrium, and endometrial hyperplasia (EH) with aberrant glandular growth. The cancer stem cells (CSCs) in the ovaries were identified based on staining with anti-mouse CD44 and anti-mouse CD133 antibodies and analysed by flow cytometry. Three different populations of ovarian CSCs: CD44+CD133-, CD44+CD133+, and CD44-CD133+, can be recognised based on the intensity of these receptors. CD44+CD133- and CD44+CD133+ cell percentages were increased in BPA-treated groups. CD44-CD133+ were increased in LD but decreased in HD. The BPA administration also induces ROS production, which decreases the expression of antioxidant genes Superoxide dismutase 1 (SOD1), Superoxide dismutase 2 (SOD2), Catalase (CAT), Glutathione peroxidase 1 (GPX1), and Forkhead box O3 (FOXO3) in ovarian cells. In conclusion, BPA exposure induced an inflammatory response, increased CSC proportions, induced ROS, and decreased antioxidant responses in the ovaries.

5.
Acta Trop ; 259: 107388, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39251172

RESUMO

Heartland virus (HRTV) is a single-stranded negative-sense RNA virus that infects human beings. Because there are no antiviral medications available to treat HRTV infection, supportive care management is used in cases of severe disease. Therefore, it has spurred research into developing a multi-epitope vaccine capable of providing effective protection against HRTV infection. A multi-epitope vaccine was created using a combination of immuno-informatics, molecular docking and molecular dynamics simulation in this investigation. The HRTV proteome was utilized to predict B-cell, T-cell (HTL and CTL), and IFN-epitopes. Following prediction, highly antigenic, non-allergenic and immunogenic epitopes were chosen, including 6 CTL, 8 HTL, and 5 LBL epitopes that were connected to the final peptide by AAY, GPGPG, and KK linkers, respectively. An adjuvant was introduced to the vaccine's N-terminal through the EAAAK linker to increase its immunogenicity. Following the inclusion of linkers and adjuvant, the final construct has 359 amino acids. The presence of B-cell and IFN-γ-epitopes validates the construct's acquired humoral and cell-mediated immune responses. To ensure the vaccine's safety and immunogenicity profile, its allergenicity, antigenicity, and various physicochemical characteristics were assessed. Docking was used to assess the binding affinity and molecular interaction between the vaccination and TLR-3. In silico cloning was used to confirm the construct's validity and expression efficiency. The results of these computer assays demonstrated that the designed vaccine is highly promising in terms of developing protective immunity against HRTV; nevertheless, additional in vivo and in vitro investigations are required to validate its true immune-protective efficiency.


Assuntos
Epitopos de Linfócito T , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Vacinas Virais , Humanos , Vacinas Virais/imunologia , Vacinas Virais/química , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/química , Biologia Computacional , Epitopos/imunologia , Epitopos/química , Bunyaviridae
6.
Parasite Immunol ; 46(8-9): e13066, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39310969

RESUMO

Obligate intracellular protozoan parasite, Leishmania donovani, causative agent of visceral leishmaniasis, led to impaired macrophage functions. It is well documented that many of these changes were induced by parasite-mediated reduction in macrophage cholesterol content. Leishmania-mediated alteration in the other lipids has not been explored in detail yet. Here, we found that the expression of key cholesterol biosynthetic genes and total cellular cholesterol were reduced during L. donovani infection. Further, we have also identified that this reduction in the cholesterol led to increased membrane fluidity and inhibition of antigen-presenting potential of macrophages. In addition to this, we studied the relative changes in different lipids in THP-1-derived macrophages during L. donovani infection through liquid chromatography-mass spectrometry. We found that Sphingomyelin (16:0) and ceramide (20:1, 26:0 and 26:1) were significantly reduced in infected macrophages. We further observed that the majority of different sub-classes of phospholipids were downregulated significantly. Overall ratio of phosphatidylcholine versus phosphotidylethanolamine was decreased which indicated the compensatory mechanism of cell in response to cholesterol reduction. The observed Leishmania-mediated alteration in macrophage-lipidome provided the novel insights into mechanism of host-pathogen interactions.


Assuntos
Colesterol , Leishmania donovani , Leishmaniose Visceral , Lipidômica , Macrófagos , Leishmania donovani/imunologia , Macrófagos/imunologia , Macrófagos/parasitologia , Macrófagos/metabolismo , Humanos , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/metabolismo , Colesterol/metabolismo , Células THP-1 , Interações Hospedeiro-Patógeno/imunologia , Metabolismo dos Lipídeos , Fluidez de Membrana
7.
Mar Environ Res ; 201: 106696, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39163655

RESUMO

To explore the variation of phytoplankton community along the Bakkhali river estuary and its adjacent coastal water in the north of the Bay of Bengal, total Chl-a (TChl-a) concentrations and group-specific photosynthetic pigments were investigated during April 2017. Distinct spatial distribution was observed in temperature, turbidity and nutrient concentrations as well as in TChl-a concentrations, showing a seaward decreasing pattern. The different distribution of phytoplankton pigments and functional groups along the gradients was also observed. Chlorophyll-b and zeaxanthin showed their highest abundance in the turbid riverine water, while alloxanthin and prasinoxanthin dominated in the coastal water. High concentrations of fucoxanthin, peridinin and hex-fucoxanthin were associated with high-light availability and showed a seaward increasing trend. Three phytoplankton groups can be classified: the riverine group (chlorophytes and cyanobacteria), the coastal group (cryptophytes and prasinophytes) and the offshore group (diatoms, dinoflagellate and haptophytes_type 6). The predominance of cryptophytes (avg. 48%) over diatoms (avg. 28%) was basically influenced by the scarcity of nitrogen and silicate relative to phosphate. Not only availability of nutrients, the photosynthetically active radiation also plays a key role in regulating TChl-a, photosynthetic pigments and functional groups in this tropical estuarine-coastal zone.


Assuntos
Monitoramento Ambiental , Estuários , Fotossíntese , Fitoplâncton , Fitoplâncton/fisiologia , Clorofila/metabolismo , Clorofila A/metabolismo , Pigmentos Biológicos/metabolismo , Clima Tropical
8.
BMJ Open ; 14(8): e082706, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39209788

RESUMO

OBJECTIVE: The COVID-19 pandemic imposed unprecedented challenges to health systems globally. This study explored slum dwellers' experience of receiving essential health services during the pandemic and the challenges faced by healthcare providers in urban areas of Bangladesh. DESIGN: The study followed a cross-sectional study design using qualitative methods. SETTING: The study was conducted in Dhaka and Gazipur City Corporations during November 2020-February 2021. PARTICIPANTS: 17 key informant interviews were carried out with healthcare providers and policy-makers and 22 in-depth interviews were carried out with slum dwellers. Thematic analysis was performed. RESULTS: The study identified challenges to the provision of essential healthcare in selected areas of Dhaka and Gazipur City Corporations during the COVID-19 pandemic. The lack of information on the availability of functional healthcare facilities, fear of contracting COVID-19 and restrictions on movement and transportation, resulted in delays in seeking essential healthcare during a pandemic. Access to healthcare facilities was further hindered by various hospitals' decision to refuse care to general patients without valid, negative COVID-19 test results. Healthcare providers identified patients' tendency to hide COVID-19 symptoms as a barrier to providing healthcare services to general patients. Conversely, patients concealed their symptoms to avoid COVID-19 tests and gain access to required treatment. In addition, the reallocation of human resources for COVID-19 treatment disrupted the delivery of essential health services. CONCLUSION: The pandemic affected the accessibility of the slum population to essential healthcare and disrupted health service delivery. The findings of the study have highlighted gaps in the health system during an emergency response period like COVID-19. The study will assist the government and other stakeholders in designing tailored interventions and allocating resources in a more efficient manner to ensure universal health coverage in the face of health emergencies.


Assuntos
COVID-19 , Acessibilidade aos Serviços de Saúde , Pesquisa Qualitativa , Humanos , COVID-19/epidemiologia , Bangladesh/epidemiologia , Estudos Transversais , População Urbana , Feminino , Pessoal de Saúde/psicologia , Masculino , SARS-CoV-2 , Adulto , Pandemias , Pobreza , Áreas de Pobreza
9.
J Card Fail ; 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39074777

RESUMO

BACKGROUND: There is conflicting data on the association between pre-orthotopic heart transplant (OHT) amiodarone use and post-OHT graft dysfunction (GD) leading to heterogeneity in clinical practice. METHODS: We performed a meta-analysis to evaluate whether pre-OHT amiodarone use was associated with meaningful increases in the incidence of GD, 30-day mortality, and 1-year mortality. Studies were identified by searching PubMed and the Cochrane Register of Clinical Trials. The Mantel-Haenszel method was used to calculate odds ratios (OR) and 95% confidence intervals (CI95) for each endpoint. RESULTS: 17 retrospective studies were identified that included 48,782 patients. 14 studies (n = 48,018) reported GD as an outcome. Pre-OHT amiodarone use was associated with increased odds of GD (OR 1.3, CI95 1.2-1.5, p < 0.001). 10 studies (n = 45,875) reported 30-day mortality based on amiodarone use. Pre-OHT amiodarone use was associated with increased odds of 30-day mortality (OR 1.4, CI95 1.2-1.5, p < 0.001). 5 studies (n = 41,404) reported 1-year mortality based on amiodarone use. Pre-OHT amiodarone use was associated with increased odds of 1-year mortality (OR 1.2, CI95 1.1-1.4, p < 0.001). The increase in absolute risk of GD, 30-day mortality, and 1-year mortality for patients with pre-OHT amiodarone use was 1.3%, 1.2%, and 1.4%, respectively. CONCLUSION: Pre-OHT amiodarone exposure was associated with increased odds of GD, 30-day mortality, and 1-year mortality. The increase in absolute risk for each endpoint was modest, and it is unclear to what extent, if any, pre-OHT amiodarone use should influence assessment of OHT candidacy.

10.
Langmuir ; 40(29): 15332-15352, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38995997

RESUMO

This study focuses on the geometrical, electronic, and optical properties of the γ-graphyne-like novel γ-SiC nanoflake of the γ-silicon carbide (SiC) monolayer using density functional theory calculations. γ-SiC was revealed to be a stable semiconducting nanoflake confirmed by a negative cohesive energy, real vibrational frequencies, and a 1.749 eV energy gap. The adsorption of COCl2, HCN, PH3, AsH3, CNCl, and C2N2 toxic gases on the γ-SiC nanoflake is also studied, which revealed an attractive gas-nanoflake interaction with the adsorption energy ranging from -0.21 to -0.38 eV. The adsorption results in a significant charge transfer between gas-adsorbent complexes. A significant variation in the energy gap and electrical conductivity was observed due to gas adsorption. γ-SiC showed maximum sensitivity at room temperature for CNCl gas. The entire process of adsorption is exothermic and thermodynamically stable. γ-SiC showed a high absorption coefficient over 104 orders with a significant variation in the absorption peak intensity and blue peak shifting. According to the quantum theory and reduced density gradient analysis, all of the gases are physisorbed on the γ-SiC nanoflake due to van der Waals interactions. The obtained results signify the usability of γ-SiC as a potential toxic gas sensor.

11.
bioRxiv ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38979231

RESUMO

Traumatic brain injury (TBI) is a significant public health concern characterized by a complex cascade of cellular events. TBI induces adenosine monophosphate-activated protein kinase (AMPK) dysfunction impairs energy balance activates inflammatory cytokines and leads to neuronal damage. AMPK is a key regulator of cellular energy homeostasis during inflammatory responses. Recent research has revealed its key role in modulating the inflammatory process in TBI. Following TBI the activation of AMPK can influence various important pathways and mechanisms including metabolic pathways and inflammatory signaling. Our study investigated the effects of post-TBI loss of AMPK function on functional outcomes inflammasome activation, and inflammatory cytokine production. Male C57BL/6 adult wild-type (WT) and AMPK knockout (AMPK-KO) mice were subjected to a controlled cortical impact (CCI) model of TBI or sham surgery. The mice were tested for behavioral impairment at 24 h post-TBI thereafter, mice were anesthetized, and their brains were quickly removed for histological and biochemical evaluation. In vitro we investigated inflammasome activation in mixed glial cells stimulated with lipopolysaccharides+ Interferon-gamma (LI) (0.1 µg/20 ng/ml LPS/IFNg) for 6 h to induce an inflammatory response. Estimating the nucleotide-binding domain, leucine-rich-containing family pyrin domain containing western blotting ELISA and qRT-PCR performed 3 (NLRP3) inflammasome activation and cytokine production. Our findings suggest that TBI leads to reduced AMPK phosphorylation in WT mice and that the loss of AMPK correlates with worsened behavioral deficits at 24 h post-TBI in AMPK-KO mice as compared to WT mice. Moreover compared with the WT mice AMPK-KO mice exhibit exacerbated NLRP3 inflammasome activation and increased expression of proinflammatory mediators such as IL-1b IL-6 TNF-a iNOS and Cox 2. These results align with the in vitro studies using brain glial cells under inflammatory conditions, demonstrating greater activation of inflammasome components in AMPK-KO mice than in WT mice. Our results highlighted the critical role of AMPK in TBI outcomes. We found that the absence of AMPK worsens behavioral deficits and heightens inflammasome-mediated inflammation thereby exacerbating brain injury after TBI. Restoring AMPK activity after TBI could be a promising therapeutic approach for alleviating TBI-related damage.

12.
Mol Biol Rep ; 51(1): 752, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874786

RESUMO

BACKGROUND: Many studies have focused on the significance of lipid regulatory genes in the pathophysiology of Coronary artery disease (CAD). ApoB XbaI (rs693) and EcoRI (rs1042031) single nucleoid polymorphisms (SNPs) were investigated to detect whether they are risk factors for CAD. Till now, this association remains uncertain. SMARCA4 (rs1122608) SNP has directly related to dyslipidemia. Loss of function mutations (LOF) in PCSK9 result in a reduction in LDL cholesterol and are associated with protection from the development of CAD. METHODS: This study was conducted on 54 CAD patients who were admitted at Internal Medicine Specialized Hospital (Cardiology Department) and 47 healthy controls. Peripheral blood samples were taken from both groups. DNA was extracted from EDTA-blood samples, then PCR- RFLP for ApoB XbaI (rs693) and EcoRI (rs1042031), SMARCA4 (rs1122608) and PCSK9 (rs505151) SNPs was done. RESULTS: No statistically significant difference was found between patients and controls as regard EcoRI SNP. XbaI (rs693) X + X + genotype was significantly higher in control group (P = 0.0355). SMARCA4 (TT, GT + TT) genotypes, and T allele (P < 0.001); PCSK9 AG genotype and G allele (P = 0.027 and 0.032 respectively) were more frequent in CAD patients than controls. CONCLUSION: SMARCA4 (rs1122608) and PCSK9 (rs505151) SNPs are significantly accompanying with the risk of CAD development in the Egyptian population. X + X + genotype appeared to have a protective effect against CAD. However, no observed association between EcoRI (rs1042031) and the risk of CAD development was found.


Assuntos
Doença da Artéria Coronariana , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Pró-Proteína Convertase 9 , Receptores de LDL , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , Apolipoproteína B-100 , Apolipoproteínas B/genética , Estudos de Casos e Controles , Doença da Artéria Coronariana/genética , Desoxirribonuclease EcoRI/genética , Egito/epidemiologia , Frequência do Gene/genética , Estudos de Associação Genética , Genótipo , População do Norte da África , Polimorfismo de Nucleotídeo Único/genética , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Fatores de Risco
13.
Front Pharmacol ; 15: 1370073, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887547

RESUMO

Introduction: There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds' anti-inflammatory effects. In this study, four xanthones ananixanthone (1), smeathxanthone A (2), smeathxanthone B (3), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (4); and three benzophenones guttiferone O (5), guttiferone M (6), and aristophenone A (7) from Garcinia smeathmannii (Planch. & Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages. Methods: The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer. Results: All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (6), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (5) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: This observation supports future exploration of ananixanthone (1), guttiferone O (5), and guttiferone (6) as potential candidates for the development of anti-inflammatory drugs.

14.
Microbes Infect ; : 105379, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38885758

RESUMO

Cholesterol reduction by intracellular protozoan parasite Leishmania donovani (L. donovani), causative agent of leishmaniasis, impairs antigen presentation, pro-inflammatory cytokine secretion and host-protective membrane-receptor signaling in macrophages. Here, we studied the miRNA mediated regulation of cholesterol biosynthetic genes to understand the possible mechanism of L. donovani-induced cholesterol reduction and therapeutic importance of miRNAs in leishmaniasis. System-scale genome-wide microtranscriptome screening was performed to identify the miRNAs involved in the regulation of expression of key cholesterol biosynthesis regulatory genes through miRanda3.0. 11 miRNAs out of 2823, showing complementarity with cholesterol biosynthetic genes were finally selected for expression analysis. These selected miRNAs were differentially regulated in THP-1 derived macrophages and in primary human macrophages by L. donovani. Correlation of expression and target validation through luciferase assay suggested two key miRNAs, hsa-miR-1303 and hsa-miR-874-3p regulating the key genes hmgcr and hmgcs1 respectively. Inhibition of hsa-mir-1303 and hsa-miR-874-3p augmented the expression of targets and reduced the parasitemia in macrophages. This study will also provide the platform for the development of miRNA-based therapy against leishmaniasis.

15.
Cureus ; 16(4): e58501, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38765368

RESUMO

Mongolian spots are bluish-grey, irregular, hyperpigmented macules present at birth or that appear in the first few weeks of life. They are classified as atypical if they occur in unusual locations without spontaneous disappearance after infancy; or if new lesions continue to appear beyond early infancy. Although they are generally considered benign, recent studies have shown that atypical Mongolian spots may be associated with inborn errors of metabolism, such as lysosomal storage disorders and neurocristopathies. An 11-month-old male presented with multiple aberrant Mongolian spots on the abdomen, back, buttocks, arms, and legs, with the largest patch measuring 10x10 cm. Additionally, the child exhibited coarse facial features, a high-arched palate, low-set ears, and a depressed nasal bridge. Systemic examination revealed hepatosplenomegaly, fundus examination showed a hazy cornea, and the urine glycosaminoglycan test was positive, prompting us to conduct further research prioritising lysosomal storage disorders. The mucopolysaccharidosis (MPS) spot test was positive, and electrophoresis for MPS revealed bands for chondroitin sulfate and dermatan sulfate, confirming the diagnosis of MPS. Enzyme assay revealed no alpha-iduronidase activity and normal beta-galactosidase activity, thus confirming Hurler's disease. This case report highlights the importance of considering atypical Mongolian spots as a potential indicator of underlying storage disorders, enabling early intervention.

16.
Cureus ; 16(4): e57409, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38694637

RESUMO

BACKGROUND: Chronic kidney disease (CKD) has emerged as a significant global health concern, with its incidence doubling over the past three decades. Cardiovascular diseases (CVD) pose a major threat to CKD patients, surpassing the risk of progressing to end-stage renal disease. While previous studies worldwide have shed light on this association, limited research has been conducted in Saudi Arabia regarding this burden. This study aims to fill this gap by identifying the prevalence and risk factors of CVD in CKD patients at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, between 2017 and 2022. METHODS: A six-year retrospective review of medical records at KAUH was conducted, including 465 non-end-stage CKD patients aged 30 to 79. Data, including demographics, clinical information, and laboratory results, were collected and statistically analyzed to investigate the association between variables. RESULTS: Out of 465 CKD patients, 262 (56.3%) were diagnosed with CVD, with congestive heart failure and ischemic heart disease being the most common types. The majority were male 259 (55.7%), non-Saudi 278 (59.8%), and aged 60 years and older 291 (62.6%). Hypertension 394 (84.7%) and diabetes mellitus 336 (72.3%) were prevalent comorbidities. Severely reduced left ventricular ejection fraction, proteinuria, diabetes mellitus, and higher BMI were identified as significant risk factors for CVD in CKD patients. CONCLUSION: This research contributes valuable insights into the prevalence and risk factors of CVD in CKD patients in Saudi Arabia, emphasizing the need for early detection and intervention. The identified risk factors provide a basis for developing targeted preventive strategies to mitigate this population's CVD burden.

17.
Dimens Crit Care Nurs ; 43(3): 136-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564456

RESUMO

BACKGROUND: Self-efficacy is an important factor associated with healthy lifestyle changes in heart failure treatment. Functional capacity testing of heart failure patients (HFPs) can stratify prognosis. Reduced functional capacities in HFPs are linked to a poor heart failure prognosis. Limited research has examined the potential relationship between self-efficacy and functional capacity. AIM: The aims of this study were to assess self-efficacy level and functional capacity among HFPs after hospitalization, and examine whether there is a relationship between them. METHODS: A descriptive correlational design was used. A convenience sample of 220 HFPs was recruited from 2 hospitals in Jordan. The Arabic version of Cardiac Self-Efficacy Questionnaire was used to assess self-efficacy, the 6-Minute Walking Test (6-MWT) was used to assess functional capacity, and the Borg rating of perceived exertion scale (Borg Scale) was used to assess exertion during 6-MWT. RESULT: The sample included 46.8% male (n = 103) and 53.2% female (n = 117). The mean age was 52.66 ± 8.91 years. Most of the HFPs were categorized based on New York Heart Association classification as class I, 35.9% (n = 79), and class II, 41.4% (n = 91). The mean ejection fraction was 41.46 ± 9.44. The global self-efficacy was moderate (32.98 ± 9.92), and the mean score for the 6-MWT was 494.35 ± 143.37. The Borg Scale mean was 10.94 ± 3.34. In addition, there was a positive relationship between self-efficacy and 6-MWT (r = 0.63, n = 220, P = .01). CONCLUSION: This study provides baseline data for further research on treatment of HFPs, and the development of evidence-based tailored health interventions to maintain and improve self-efficacy and functional capacity among these service users. Moreover, replicated researches can test the study results considering different methodologies, such as using objective functional capacity tool and longer follow-up periods.


Assuntos
Teste de Esforço , Insuficiência Cardíaca , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Teste de Esforço/métodos , Alta do Paciente , Autoeficácia , Jordânia
18.
J Pharm Bioallied Sci ; 16(Suppl 1): S56-S59, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595522

RESUMO

The rise of Islam in Arabia witnessed a scientific pursuit from 8th CE to 14th CE in its vast dominion. Medicine was one among many disciplines that was reshaped during the golden ages of Islamic world. Physicians and scholars from diverse faiths and background flocked in learning centers of Baghdad, Cordoba, and other cities. A multicultural environment of medical research was evolved with fundings from state. From medical teaching and clinical training to the licensing of physicians, many of the modern attributes of medical education were pioneered in Islamic world. The scholarly transfusion from European territories of Islamic world to the Western world in medieval era laid the foundation of modern medical education.

19.
JMIR Form Res ; 8: e49815, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656783

RESUMO

BACKGROUND: Since 2016, the government of Bangladesh has been piloting a health protection scheme known as Shasthyo Surokhsha Karmasuchi (SSK), which specifically targets households living below the poverty line. This noncontributory scheme provides enrolled households access to inpatient health care services for 78 disease groups. Understanding patients' experiences with health care utilization from the pilot SSK scheme is important for enhancing the quality of health care service delivery during the national-level scale-up of the scheme. OBJECTIVE: We aimed to evaluate patient satisfaction with the health care services provided under the pilot health protection scheme in Bangladesh. METHODS: A cross-sectional survey was conducted with the users of the SSK scheme from August to November 2019. Patients who had spent a minimum of 2 nights at health care facilities were selected for face-to-face exit interviews. During these interviews, we collected information on patients' socioeconomic characteristics, care-seeking experiences, and level of satisfaction with various aspects of health care service delivery. To measure satisfaction, we employed a 5-point Likert scale (very satisfied, 5; satisfied, 4; neither satisfied nor dissatisfied, 3; dissatisfied, 2; very dissatisfied, 1). Descriptive statistics, statistical inferential tests (t-test and 1-way ANOVA), and linear regression analyses were performed. RESULTS: We found that 55.1% (241/438) of users were either very satisfied or satisfied with the health care services of the SSK scheme. The most satisfactory indicators were related to privacy maintained during diagnostic tests (mean 3.91, SD 0.64), physicians' behaviors (mean 3.86, SD 0.77), services provided at the registration booth (mean 3.86, SD 0.62), confidentiality maintained regarding diseases (mean 3.78, SD 0.72), and nurses' behaviors (mean 3.60, SD 0.83). Poor satisfaction was identified in the interaction of patients with providers about illness-related information (mean 2.14, SD 1.40), availability of drinking water (mean 1.46, SD 0.76), cleanliness of toilets (mean 2.85, SD 1.04), and cleanliness of the waiting room (mean 2.92, SD 1.09). Patient satisfaction significantly decreased by 0.20 points for registration times of 16-30 minutes and by 0.32 points for registration times of >30 minutes compared with registration times of ≤15 minutes. Similarly, patient satisfaction significantly decreased with an increase in the waiting time to obtain services. However, the satisfaction of users significantly increased if they received a complete course of medicines and all prescribed diagnostic services. CONCLUSIONS: More than half of the users were satisfied with the services provided under the SSK scheme. However, there is scope for improving user satisfaction. To improve the satisfaction level, the SSK scheme implementation authorities should pay attention to reducing the registration time and waiting time to obtain services and improving the availability of drugs and prescribed diagnostic services. The authorities should also ensure the supply of drinking water and enhance the cleanliness of the facility.

20.
Int J Nanomedicine ; 19: 3461-3473, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617799

RESUMO

Purpose: Ivosidenib (IVO), an isocitrate dehydrogenase-1 (IDH1) used for treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. However, poor solubility, low bioavailability, high dose and side effects limit clinical application of IVO. Methods: Ivosidenib-loaded PLGA nanoparticles (IVO-PLGA-NPs) and Ivosidenib-loaded chitosan coated PLGA nanoparticles (IVO-CS-PLGA-NPs) were prepared using emulsification and solvent evaporation method for the treatment of liver cancer. Results: The developed IVO-PLGA-NPs were evaluated for their particle size (171.7±4.9 nm), PDI (0.333), ZP (-23.0±5.8 mV), EE (96.3±4.3%), and DL (9.66±1.1%); similarly, the IVO-CS-PLGA-NPs were evaluated for their particle size (177.3±5.2 nm), PDI (0.311), ZP +25.9±5.7 mV, EE (90.8±5.7%), and DL (9.42±0.7%). The chitosan coating of IVO-PLGA-NPs was evidenced by an increase in mean particle size and positive ZP value. Because of the chitosan coating, the IVO-CS-PLGA-NPs showed a more stable and prolonged release of IVO than IVO-PLGA-NPs. In comparison to pure-IVO, the IVO-PLGA-NPs and IVO-CS-PLGA-NPs were found to be more effective against HepG2 cells, with IC50 values for the MTT assay being approximately half of those of pure-IVO. In HepG2 cells, the expressions of caspase-3, caspase-9, and p53 were significantly (p < 0.05) elevated. Conclusion: Overall, these findings suggest that chitosan coating of IVO-PLGA-NPs improves the delivery and efficacy of ivosidenib in liver cancer treatment.


Assuntos
Neoplasias dos Ductos Biliares , Quitosana , Glicina/análogos & derivados , Neoplasias Hepáticas , Nanopartículas , Piridinas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Ductos Biliares Intra-Hepáticos
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