RESUMO
Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the genus Alphavirus and is responsible for causing Chikungunya fever, a type of arboviral fever. Despite extensive research, the pathogenic mechanism of CHIKV within host cells remains unclear. In this study, an in-silico approach was used to predict that CHIKV produces micro-RNAs that target host-specific genes associated with host cellular regulatory pathways. Putative micro-RNAs of CHIKV were predicted using the miRNAFold and Vmir RNA structure web servers, and secondary structure prediction was performed using RNAfold. Host-specific target genes were then predicted, and hub genes were identified using CytoHubba and module selection through MCODE. Functional annotations of hub genes revealed their association with various pathways, including osteoclast differentiation, neuroactive ligand-receptor interaction, and mRNA surveillance. We used the freely available dataset GSE49985 to determine the level of expression of host-specific target genes and found that two genes, F-box and leucine-rich repeat protein 16 (FBXL16) and retinoic acid receptor alpha (RARA), were down-regulated, while four genes, RNA binding protein with serine-rich domain 1 (RNPS1), RNA helicase and ATPase (UPF1), neuropeptide S receptor 1 (NPSR1), and vasoactive intestinal peptide receptor 1 (VIPR1), were up-regulated. These findings provide insight into novel miRNAs and hub genes associated with CHIKV infection and suggest potential targets for therapeutic intervention. Further experimental validation of these targets could lead to the development of effective treatments for CHIKV-mediated diseases.
Assuntos
Vírus Chikungunya , Biologia Computacional , MicroRNAs , Vírus Chikungunya/genética , Vírus Chikungunya/imunologia , MicroRNAs/genética , Biologia Computacional/métodos , Humanos , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Febre de Chikungunya/virologia , Febre de Chikungunya/imunologia , Febre de Chikungunya/genética , RNA Viral/genética , Redes Reguladoras de GenesRESUMO
In our study, we examined the efficacy of mTOR (mammalian target of rapamycin) inhibitors, specifically rapamycin (Rap), compared to calcineurin inhibitors (CNIs) in kidney transplantation. By conducting a comprehensive search across reputable databases (EMBASE, Scopus, PubMed, Cochrane, and Crossref), we gathered data for a six-month post-transplantation period. Our analysis revealed that mTOR inhibitor administration resulted in improved glomerular filtration rate (GFR) and serum creatinine levels. However, it is important to note that the mTOR inhibitor group had a higher incidence of acute rejection after biopsy. Through molecular modeling, we observed that Rap exhibited a superior binding affinity for mTOR compared to CNIs' binding to calcineurin, probably contributing to the transplant rejection. Our meta-analysis supports the cautious use of an optimal mTOR inhibitor in conjunction with careful consideration of clinical features when minimizing CNIs early in the transplantation process. This is because mTOR inhibitors have complementary mechanisms of action, a low nephrotoxicity profile, and favorable outcomes in serum creatinine and GFR, which contribute to improved transplant survival.
Assuntos
Transplante de Rim , Humanos , Imunossupressores/uso terapêutico , Inibidores de MTOR , Calcineurina , Creatinina , Inibidores de Calcineurina/uso terapêutico , Sirolimo , Serina-Treonina Quinases TOR , Rim , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/etiologiaRESUMO
INTRODUCTION AND IMPORTANCE: Burkitt lymphoma (BL) is an aggressive subtype of non-Hodgkin lymphoma with a predilection for pediatric patients, known for its rapid growth and MYC oncogene-associated chromosomal translocations. CASE PRESENTATION: A 33-year-old male presented with a perineal ulcerated wound, initially misdiagnosed as a musculoskeletal injury. Imaging and histopathological analysis eventually confirmed BL, leading to the initiation of high-dose chemotherapy. CLINICAL DISCUSSION: BL is characterized by its rapid growth, typically as masses in the abdomen or jaw. Nevertheless, atypical presentations can lead to diagnostic delays, underscoring the importance of considering BL even in the absence of classic symptoms. Swift recognition and accurate diagnosis are critical for initiating timely chemotherapy. Comprehensive clinical evaluation, advanced imaging, and histopathological analysis are pivotal in confirming the diagnosis. CONCLUSION: This unique case of BL with a perineal mass presentation emphasizes the necessity of considering BL as a potential diagnosis in atypical cases, highlighting the importance of early recognition and appropriate therapeutic strategies. Healthcare professionals should be aware of the potential for unusual BL presentations.
RESUMO
The liver plays a critical role in metabolic processes, making it vulnerable to injury. Researchers often study carbon tetrachloride (CCl4)-induced hepatotoxicity in model organisms because it closely resembles human liver damage. This toxicity occurs due to the activation of various cytochromes, including CYP2E1, CYP2B1, CYP2B2, and possibly CYP3A, which produce the trichloromethyl radical (CCl3*). CCl3* can attach to biological molecules such as lipids, proteins, and nucleic acids, impairing lipid metabolism and leading to fatty degeneration. It can also combine with DNA to initiate hepatic carcinogenesis. When exposed to oxygen, CCl3* generates more reactive CCl3OO*, which leads to lipid peroxidation and membrane damage. At the molecular level, CCl4 induces the release of several inflammatory cytokines, including TNF-α and NO, which can either help or harm hepatotoxicity through cellular apoptosis. TGF-ß contributes to fibrogenesis, while IL-6 and IL-10 aid in recovery by minimizing anti-apoptotic activity and directing cells toward regeneration. To prevent liver damage, different interventions can be employed, such as antioxidants, mitogenic agents, and the maintenance of calcium sequestration. Drugs that prevent CCl4- induced cytotoxicity and proliferation or enhance CYP450 activity may offer a protective response against hepatic carcinoma.
RESUMO
OBJECTIVE: To estimate the relationship between household income and child health outcomes for male and female children, aged 0-5 years, in rural Pakistan. METHOD: The study uses 2014 round of Pakistan Rural Household Panel Survey (PRHPS) and regression analyses to estimate the relationship between household income and child health outcomes for male and female children in rural Pakistan. RESULTS AND POLICY IMPLICATIONS: We find that increase in income is associated with an increase in child weight-for-age and weight-for-height z-scores, and reduction in the likelihood of a child being underweight or wasted. However, our results suggest that these gains associated with an increase in income are greater for male children as compared to female children. These differences in income-nutrition gradient can be explained by the gender-differences in consumption of health inputs (e.g., food intake, vaccinations, and nutritional supplements) associated with an increase in income. Our results indicate the need for policy instruments that can encourage an equitable resource allocation within households.
This study documents the gender bias in income-health relationship for children in rural Pakistan. Our results imply that interventions that target poverty alleviation at the household level may not have equitable impacts on all members of the household because of possible 'son-preference'. This suggests that there is a need to design gender-sensitive interventions to ensure that improvements in nutritional outcomes are shared across genders within households.
Assuntos
Renda , Estado Nutricional , Criança , Humanos , Masculino , Feminino , Paquistão , População Rural , MagrezaRESUMO
Objectives. To evaluate the impact of a community health worker-based "in-home growth monitoring with counseling" (IHGMC) intervention on anthropometric outcomes in Pakistan, where 38% of children younger than 5 years are stunted. Methods. We used an individual, single-blind, step-wedge randomized controlled trial and a pure control group recruited at endline. We based the analysis on an intention-to-treat estimation using the coarsened exact matching (CEM) method for sample selection among treatments and the control. We conducted the baseline in July 2019 and completed endline in September-October 2021. We recruited 1639 households (treated: 1188; control: 451) with children aged 3 to 21 months who were residing in an urban informal settlement area. The CEM sample used for analysis numbered 1046 (treated: 636; control: 410). The intervention continued for 6 months. Results. Compared with the control group, the height-for-age z-score in the IHGMC group increased by 0.58 SD (95% confidence interval [CI] = 0.33, 0.83; P = .001) and the weight-for-age z-score by 0.43 SD (95% CI = 0.20, 0.67; P < .01), measured at endline. Conclusions. IHGMC substantially improved child anthropometric outcomes in disadvantaged localities, and this impact persisted during the COVID-19 pandemic. Trial Registration. AER-RCT registry (AEARCTR-0003248). (Am J Public Health. 2023;113(1):105-114. https://doi.org/10.2105/AJPH.2022.307111).
Assuntos
COVID-19 , Agentes Comunitários de Saúde , Criança , Humanos , Método Simples-Cego , Paquistão , PandemiasRESUMO
Nanocrystals are carrier-free, submicron-sized, colloidal drug delivery systems with particle sizes in the mean nanometer range. Nanocrystals have high bioavailability and fast absorption because of their high dissolution velocity and enhanced adhesiveness to cell membranes. Loxoprofen, a nonsteroidal anti-inflammatory drug belonging to the Biopharmaceutical Classification System (BCS) II drug class, was selected as the model drug. The aim of this study was to formulate nanocrystals of loxoprofen. A total of 12 formulations (F1 to F12) were prepared. An antisolvent technique was used to determine the effects of various stabilizers and processing conditions on the optimization of formulations. The various stabilizers used were hydroxypropyl methylcellulose (0.5%), polyvinylpyrrolidone (0.5%), and sodium lauryl sulfate (0.1%). The various characterizations conducted for this research included stability studies at 25 °C and 4 °C, scanning electron microscopy, transmission electron microscopy (TEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), zeta potentials, polydispersity indexes, and dissolution studies. F10 was the optimized formulation that showed stability at room temperature, as well as at a refrigerated temperature, for 30 days. A high dissolution rate (100% within the first 10 min) was shown by comparative dissolution studies of nano-suspensions with the micro-suspension and raw loxoprofen. F10 formulation had a non-porous and crystalline morphology on evaluation by TEM and XRPD, respectively, and the average particle size was 300 ± 0.3 nm as confirmed by TEM. DSC recorded a reduction in the melting point (180 °C processed and 200 °C unprocessed melting points). The dissolution rate and solubility of the formulated loxoprofen nanocrystals were significantly enhanced. It can be concluded that selecting suitable stabilizers (i.e., polymers and surfactants) can produce stable nanocrystals, and this can potentially lead to a scaling up of the process for commercialization.
RESUMO
INTRODUCTION AND IMPORTANCE: Ewing sarcomas are a group of small round cell tumors that occur predominantly in the long bones as well as in extraosseous locations such as the extremities, trunk, and retroperitoneum (Gier, 1997) [2]. Extraosseous Ewing sarcoma (EES) is a type of small round cell tumor that occurs in soft tissues. I rare cases, EES occurs in the esophagus (Maesawa et al., 2002; Johnson et al., 2010) [1,3]. Ewing's sarcoma is a rare and highly aggressive cancer most frequently arising in people under 20 years of age. We report an uncommon case of primary paraesophageal Ewing's sarcoma in a 25-year-old female. CASE PRESENTATION: A 26 years old Asian female referred primarily for surgical treatment due to esophageal cancer detected on her diagnostic investigations and revealed a primary tumor located near the gastroesophageal junction. Based on the results of diagnostic investigations which confirmed the possibility of the tumor Ewing sarcoma of esophagus, which was biopsy and immune histochemical stain proven the patient was qualified for surgical treatment. She underwent Mckewon esophagectomy on October 2021 for Ewing sarcoma of esophagus. She was first followed with neoadjuvant intravenous chemotherapy, after taking three cycles of neoadjuvant chemo showed good response in CT scan the patient underwent Mckewon esophagectomy, post op recovery was smooth she underwent 2 cycles of adjuvant chemotherapy after four months of surgery. Her followup visit was uneventful. CLINICAL DISCUSSION: Ewing's sarcoma is the second most frequent primary malignant bone cancer, after osteosarcoma. It was first described by James Ewing in 1921, as an undifferentiated tumor developing in the diaphysis of the ulna of a young female patient (Ushigome et al., 2002) [6]. Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), previously thought to be separate tumors, is now treated as the same tumor; both have similar immunohistochemical characteristics and chromosomal translocation (Maesawa et al., 2002) [1]. They are malignant tumors composed of undifferentiated small round cells, usually affecting children, adolescents, and young adults (Kondo et al., 2005) [7]. Generally ES/PNET affects the bones and deep soft tissues (Soulard et al., 2005) [8], although other organs such as the pancreas, small bowel, esophagus, kidneys, prostate, ovaries, vagina and rectovaginal septum have been reported; this is termed as extraskeletal ES/PNET (Bloom et al., 1995) [9]. To the best of our knowledge, only 5 cases of gastric ES/PNET have been reported in the English language literature. Extraskeletal Ewing's sarcoma is a very rare disease, accounting for 6 %-47 % of all cases of Ewing's sarcoma. It is mainly diagnosed in the trunk, extremities, retroperitoneum, and head and neck region. Patients with extraosseous Ewing's sarcoma are more likely to be older, female, and not of Caucasian origin. An extraskeletal origin of the disease is correlated to poor prognosis (Siegel et al., 1988; Granowetter and West, 1997; Ushigome et al., 2002) [4-6]. We present an uncommon case of extraskeletal Ewing's sarcoma, and discuss its rare presentation and evolution. To our knowledge, this is the first reported case of paraesophageal primary Ewing's sarcoma and primitive neuroectodermal tumor. Adenocarcinoma and squamous cell carcinoma account for the vast majority of esophageal malignancies. Other malignancies known to occur in the esophagus include melanoma, sarcoma, and lymphoma. Among the sarcomas, carcinosarcoma is the commonest with both carcinomatous and sarcomatous elements followed by leiomyosarcoma of mesenchymal origin. Other sarcomas reported in the literature are liposarcoma, synovial sarcoma, myxofibrosarcoma, Ewing's sarcoma, granulocytic sarcoma, histiocytic sarcoma, schwannoma rhabdomyosarcoma, and epithelioid sarcoma. CONCLUSION: Ewing sarcoma is a rare entity among all esophageal malignancies. It presents as an exophytic mass, and in this case, it has presented as a mass occluding the lumen of esophagus. Most of these tumors present in locally advanced and disseminated condition, one of the reasons being difficulty and hence delay in diagnosis. In spite of best efforts, a group among them remains to be histologically uncharacterized.
RESUMO
The UN has declared universal health coverage an urgent global goal. Efforts to achieve this goal have been supported by rigorous research on the scientific, technical, and administrative aspects of health systems design. Yet a substantial portion of the world's population does not have access to essential health services. There is growing recognition that achieving universal health coverage is a political challenge. However, fundamental concepts from the political science discipline are often overlooked in the health literature. This Series paper draws on political science research to highlight the ways in which politics can facilitate, or stymie, policy reform. Specifically, we present a framework of analysis that explores how interests, ideas, and institutions shape universal health coverage. We then examine key considerations relating to the implementation of relevant policies. This Series paper shows that a political understanding of universal health coverage is needed to achieve health for all.
Assuntos
Reforma dos Serviços de Saúde , Cobertura Universal do Seguro de Saúde , Humanos , Políticas , PolíticaRESUMO
The coronavirus (SARS-CoV-2) pandemic is rapidly advancing and spreading worldwide, which poses an urgent need to develop anti-SARS-CoV-2 agents. A human receptor, namely, angiotensin-converting enzyme 2 (ACE-2), supports the SARS-CoV-2 entry, therefore, serves as a target for intervention via drug. In the current study, bioinformatic approaches were employed to screen potent bioactive compounds that might be ACE-2 receptor inhibitors. The employment of a docking study using ACE receptor protein with a ready-to-dock database of phytochemicals via MOE software revealed five compounds as potent molecules. Among them, astragaloside exhibited the highest binding affinity -21.8 kcal/mol and stable interactions within the active site of the ACE-2 receptor. Similarly, the phytochemicals such as pterocaryanin B, isoastragaloside II, and astraisoflavan glucoside followed by oleuropein showed a stronger binding affinity. We hypothesize these compounds as potential lead candidates for the development of anti- COVID-19 target-specific drugs.
Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Humanos , SARS-CoV-2 , Pandemias , Compostos Fitoquímicos/farmacologia , Simulação de Acoplamento Molecular , Antivirais/químicaRESUMO
OBJECTIVE: To determine the frequency of breakthrough seizures among paediatric patients suffering from epilepsy, and factors related to the precipitation of these seizures. METHODS: The cross-sectional study was conducted from July 1, 2018, to July 1, 2020, at the Combined Military Hospital Lahore and the Military Hospital, Rawalpindi, Pakistan, and comprised children of either gender aged 2-12 years diagnosed with any type of epilepsy presenting at the children outpatient department. Diagnosis of epilepsy was established by either a consultant adult neurophysician or a consultant paediatrician. The presence of breakthrough seizures was assessed by obtaining detailed history from the patient and the primary caregiver. Socio-demographic profile, duration of epilepsy and poly-pharmacy were noted. Data was analysed using SPSS 23. RESULTS: Of the 450 subjects, 259(57.6%) were boys and 191(42.4%) were girls. The overall mean age was 6.353±4.732 years. The presence of breakthrough seizures was noted in 227(50.4%) subjects. Children with young age, with low family income, and those in need of poly-pharmacy showed significantly higher odds for breakthrough seizures (p<0.05). CONCLUSIONS: The incidence of breakthrough seizures in epileptic children was high despite the anticonvulsant agents that were previously effective in controlling seizures.
Assuntos
Epilepsia , Adulto , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Estudos Transversais , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Convulsões/complicaçõesRESUMO
BACKGROUND: Hepatitis C Virus (HCV) is one of the serious health issues affecting onethird of the world's population. The high variations of the HCV genome are ascribed to quick replication by NS5B polymerase and are thus the most attractive target for developing anti-HCV agents. OBJECTIVE: The current study aimed to discover novel phytochemicals that harbor the potential of NS5B polymerase inhibition. METHODS: In this computational study, a molecular docking approach was used to screen phytochemicals with the best binding and spatial affinity with NS5B at the Palm I region. The topranked compounds were then subjected to an in-silico pharmacokinetic and toxicological study. RESULTS: The virtual screening provided seven 'hit compounds' including Betanin, 3,5'- dihydroxythalifaboramine, Diarctigenin, 6'-desmethylthalifaboramine, Cephalotaxine, 5alpha-O- (3'-dimethylamino-3'-phenylpropionyl) taxinine M and IsoTetrandrine with minimum binding score compared to the reference drug, sofosbuvir (-14.7 kcal/mol). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) and thorough toxicological analysis revealed a favorable safety profile of these compounds. CONCLUSION: The study demonstrates the identified phytochemicals. These may serve as potential antiviral compounds that can provide an alternative approach for amelioration of HCV.
Assuntos
Hepacivirus , Hepatite C , Antivirais/química , Antivirais/farmacologia , Hepatite C/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismoRESUMO
The current study focuses on the fabrication of calcium hydroxyapatite (Ca10(PO4)6(OH)2) (HA) in a nanorange having whiskers- and cubic-shaped uniform particle morphology. The synthesized HA particles hold a promising feature as reinforcement fillers in dental acrylic resin composite. They increase the efficacy of reinforcement by length and aspect ratio, uniformity, and monodispersity. Therefore, the acrylic resin was reinforced with the as-synthesized monodispersed HA filler particles (0.2-1 Wt%). The presence of filler particles in the composite had a noticeable effect on the tribological and mechanical properties of the dental material. The morphological effect of HA particles on these properties was also investigated, revealing that cubic-shaped particles showed better results than whiskers. The as-fabricated composite (0.4 Wt%) of the cubic-shaped filler particles showed maximum hardness and improved antiwear/antifriction properties. Particle loading played its part in determining the optimum condition, whereas particle size also influenced the reinforcement efficiency. The current study revealed that particle morphology, particle size, uniformity, etc., of HA fillers, greatly influenced the tribological and mechanical properties of the acrylic resin-based nanocomposite. Improvement in the tribological properties of HA particle-reinforced acrylic resin composites (HA-acrylic resin) followed the trend as AR < CmC < WC < CC.
Assuntos
Restauração Dentária Permanente/instrumentação , Durapatita/farmacologia , Resinas Sintéticas , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Resinas Compostas/síntese química , Resinas Compostas/química , Durapatita/química , Dureza , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Nanocompostos/química , Nanopartículas/química , Resinas Sintéticas/síntese química , Resinas Sintéticas/química , Resinas Sintéticas/farmacologia , Propriedades de SuperfícieRESUMO
INTRODUCTION AND IMPORTANCE: Amyand's hernia (AH) is a form of inguinal hernia which is consider as very rare and this type of hernia occurred up to 1% of all inguinal hernia cases. In this type of inguinal hernia, the content of hernia sac is appendix. Most patient with AH often remains asymptomatic and diagnosed intraoperatively. The diagnosis is challenging, since needs a high index of suspicion and imaging is key. Surgery is the mainstay management. We report a case of Amyand's hernia that was managed operatively in our medium complex public institution. CASE PRESENTATION: A 28 year's old man with normal body mass index (BMI) who had a history of right-side reducible linguino-scrotal swelling for 8 years, was admitted for elective right inguinal hernia repair. Two weeks back before admission, he noticed that swelling was slightly painful. Ultrasound of the abdomen reported normal findings. There was no history of abdominal pain and vomiting. Laboratory parameters were within normal limit. So, with a diagnosis of right sided partially reducible, incomplete, and indirect inguinal hernia, patient was operated for open hernia repair surgery, intra operatively we found dense adhesions within the sac, adhesions were released which revealed herniation of appendix into the inguinal canal. Appendix was mildly congested without gross evidence of inflammation. Hence, in view of noninflamed appendix, preperitoneal mesh (polypropylene) hernioplasty from Lichtenstein tension-free mesh repair was performed with appendicectomy. Postoperative period was uneventful, patient discharged at second day. CLINICAL DISCUSSION: Amyand's hernia is very uncommon and characterized by the presence of the appendix in the hernia sac and it is 0.4-1% of all inguinal hernia cases, literature review also showed that incidence of Amyand's hernia is very rare, whereas only 0.1% of cases complicate into acute appendicitis due to late presentation and missed diagnosis. CONCLUSION: Amyand's hernia (AH) makes up only a small proportion of most inguinal hernia cases, and its diagnosis is usually based on incidental finding intra-operatively. This condition may remain asymptomatic and behave like a normal inguinal hernia. Management of this type of hernia should be individualized according to appendix's inflammation stage, presence of abdominal sepsis and co-morbidity. With this approach it enables surgeons to manage more variations of Amyand's hernia. Laparoscopy for dealing Amyand's hernia is frequently diagnostic as well as therapeutic.
RESUMO
OBJECTIVE: To assess the presence of psychiatric morbidity and associated socio-demographic factors among informal caregivers of children suffering from intellectual developmental disorders. METHODS: The analytical cross-sectional study was conducted at the Neurology Department of a tertiary care hospital in Rawalpindi, Pakistan, from January 1, 2018, to December 31, 2019, and comprised informal caregiver of children diagnosed with intellectual developmental disorders presenting at the paediatric or neurology outpatient clinics of the hospital. Intellectual developmental disorder was diagnosed by consultant neurologists or psychiatrists or paediatricians on the basis of International Classification of Diseases-11 criteria. Psychiatric morbidity in the informal caregiver was assessed using the 12-item general health questionnaire. Data was analysed using SPSS 23, and binary logistic regression was applied to assess association. RESULTS: Of the 500 informal caregivers, 323(64.6%) showed psychiatric morbidity. Increasing age and comorbid epilepsy among the patients were significantly related to the presence of psychiatric morbidity among the informal caregivers (p<0.05). CONCLUSIONS: Majority of informal caregivers of children with learning difficulties were found to have psychiatric morbidity.
Assuntos
Cuidadores , Deficiência Intelectual , Criança , Estudos Transversais , Deficiências do Desenvolvimento/epidemiologia , Humanos , Deficiência Intelectual/epidemiologia , MorbidadeRESUMO
Hepatitis C Virus (HCV) is a viral infection posing a severe global threat that left untreated progresses to end-stage liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Moreover, no prophylactic approach exists so far enabling its prevention. The NS5B polymerase holds special significance as the target of intervention against HCV infection. The current study kindles benzothiazine derivatives against HCV NS5B polymerase through in silico and experimental approaches. Following docking, the compound 2-(3,4-dimethyl-5,5-dioxidobenzo[e]pyrazolo[4,3-c][1,2]thiazin-2(4H)-yl)-N-(2-fluorobenzyl)acetamide was revealed to form effective binding interaction in the proposed site of HCV NS5B with a score of -10 kcal/mol and subsequently was deciphered through molecular dynamics (MD) simulation study which indicated interaction of residues TYR_382, VAL_381 and HIS_467 through hydrophobic interaction and two residues such as GLU_202 and LYS_209 contributed in the formation of water bridges. The subsequent in silico pharmacological analysis revealed its safe drug profile. The cytotoxicity activity of compound 6c indicated to be non-toxic in HepG2 cells at concentration ranges from 0.001-1.0 µmol/L with >80% cell viability and diminished expression of the HCV NS5B to 98% at the dose of 1.0 µmol/L and 90% at 0.5µmol/L. Thus the hit compound 6c might be a potent NS5B polymerase inhibitor required to be validated further through in vivo and preclinical studies.
Assuntos
HepacivirusRESUMO
Aims & Objective: Armoracia rusticana has high medicinal values and is an excellent source of phytochemicals. This study was aimed to evaluate the antidiabetic potential of bioactive compounds from Armoracia rusticana. METHODS: The antidiabetic analysis revealed that Armoracia rusticana was highly active against α- glucosidase with IC50 values of 5.6 µg/ml. Furthermore, molecular docking was used to identify the active constituents against α-glucosidase, while using acarbose as a controlled drug. RESULTS: Upon phytochemical screening, it was found that six out of ten phytochemicals were successfully docked in the respective binding sites. The lead phytochemical was Quercetin 3-Obeta- D-xylopyranoside, which displayed a more binding score as compared to acarbose. They were subjected to analyze for drug-like properties, which further strengthen its validation. CONCLUSION: It was, therefore, concluded that Armoracia rusticana might potentially be used in the amelioration of type 2 diabetes. Potential molecules identified from this study could be considered as a lead drug to cure diabetes mellitus.
Assuntos
Armoracia/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , alfa-Glucosidases/metabolismoRESUMO
OBJECTIVES: To characterise the ion release, pH changes and apatite formation of a phosphate free bioactive glass. METHODS: A SiO2-CaO-CaF2-Na2O glass was synthesized by a melt route with a composition close to the reactive glass in the commercial Cention N® composite. The glass was characterized after immersion in three media: Artificial Saliva pH4 (AS4) Artificial Saliva pH7 (AS7) and in a high phosphate artificial saliva at pH6.5 (AS6.5). The pH and fluoride release were measured using a pH meter and an ion selective electrode. The concentration of Ca, P, Na and Si were measured by ICP-OES. The glass powders after immersion were characterized by FTIR, X-ray powder diffraction and 19F MAS-NMR. RESULTS: The glass increased the pH in all three media. Fluoride was detected in all three media but was much higher in AS 6.5. Calcium fluoride formed in AS4 with a small amount of fluorapatite at long immersion times. Fluorapatite and calcium fluoride formed in AS7, whilst in AS6.5 fluorapatite formed. The ion concentrations in solution after immersion reflected the glass composition and the immersion media with fluorapatite being favoured by higher pHs and phosphate contents in the media. SIGNIFICANCE: The results demonstrated the ability of the glass to increase the pH and to form fluorapatite in phosphate containing media. This may explain the low incidence of secondary caries found in the commercial composite. Unlike the commercial composite evidence was found for the precipitation of fluorite, which will act to reduce the release of fluoride for preventing secondary caries.
Assuntos
Vidro , Dióxido de Silício , Fluoretos , Fosfatos , Saliva ArtificialRESUMO
Document analysis is one of the most commonly used and powerful methods in health policy research. While existing qualitative research manuals offer direction for conducting document analysis, there has been little specific discussion about how to use this method to understand and analyse health policy. Drawing on guidance from other disciplines and our own research experience, we present a systematic approach for document analysis in health policy research called the READ approach: (1) ready your materials, (2) extract data, (3) analyse data and (4) distil your findings. We provide practical advice on each step, with consideration of epistemological and theoretical issues such as the socially constructed nature of documents and their role in modern bureaucracies. We provide examples of document analysis from two case studies from our work in Pakistan and Niger in which documents provided critical insight and advanced empirical and theoretical understanding of a health policy issue. Coding tools for each case study are included as Supplementary Files to inspire and guide future research. These case studies illustrate the value of rigorous document analysis to understand policy content and processes and discourse around policy, in ways that are either not possible using other methods, or greatly enrich other methods such as in-depth interviews and observation. Given the central nature of documents to health policy research and importance of reading them critically, the READ approach provides practical guidance on gaining the most out of documents and ensuring rigour in document analysis.