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1.
Mol Neurobiol ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890237

RESUMEN

Multiple sclerosis (MS) is a neurodegenerative disease characterized by the demyelination of nerves, axonal damage, and neuroinflammation. Cognition impairment, pain, and loss of mobility are some of the usual complications of MS. It has been postulated that the overproduction of proinflammatory cytokines and reactive oxygen species (ROS) are the main factors that contribute to MS pathology. Among various animal models, the cuprizone model is the most widely used model for investigating MS-related pathology. We assessed the effects of cuprizone along with the protective effects of some black seed oil-based nanoformulations of curcumin with and without piperine, in mice hippocampus in terms of the changes in antioxidant enzymes, transcription factors, and cytokines during demyelination and remyelination processes. The results of behavioral studies point toward impairment in working memory following the feeding of cuprizone for 5 weeks. However, in treatment groups, mice seemed to prevent the toxic effects of cuprizone. Nanoformulations used in this study were found to be highly effective in lowering the amount of ROS as indicated by the levels of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione peroxidase. Moreover, nanoformulations CCF and CCPF were observed resisting the toxic effects of cuprizone. We observed greater expression of NFκB-p65 in the CPZ group than in the control group. CCF nanoformulation had a better inhibitory effect on NFκB-p65 than other formulations. Histological examination of the hippocampus was also conducted. Nanoformulations used here were found effective in reversing MS-related pathophysiology and hence have the potential to be applied as adjuvant therapy for MS treatment.

2.
Head Neck ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38779999

RESUMEN

BACKGROUND: Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC. METHODS: For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test. RESULTS: Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). CONCLUSION: Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

3.
Pharmaceuticals (Basel) ; 17(5)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38794151

RESUMEN

Background: The hunt for naturally occurring antiviral compounds to combat viral infection was expedited when COVID-19 and Ebola spread rapidly. Phytochemicals from Nyctanthes arbor-tristis Linn were evaluated as significant inhibitors of these viruses. Methods: Computational tools and techniques were used to assess the binding pattern of phytochemicals from Nyctanthes arbor-tristis Linn to Ebola virus VP35, SARS-CoV-2 protease, Nipah virus glycoprotein, and chikungunya virus. Results: Virtual screening and AutoDock analysis revealed that arborside-C, beta amyrin, and beta-sitosterol exhibited a substantial binding affinity for specific viral targets. The arborside-C and beta-sitosterol molecules were shown to have binding energies of -8.65 and -9.11 kcal/mol, respectively, when interacting with the major protease. Simultaneously, the medication remdesivir exhibited a control value of -6.18 kcal/mol. The measured affinity of phytochemicals for the other investigated targets was -7.52 for beta-amyrin against Ebola and -6.33 kcal/mol for nicotiflorin against Nipah virus targets. Additional molecular dynamics simulation (MDS) conducted on the molecules with significant antiviral potential, specifically the beta-amyrin-VP35 complex showing a stable RMSD pattern, yielded encouraging outcomes. Conclusions: Arborside-C, beta-sitosterol, beta-amyrin, and nicotiflorin could be established as excellent natural antiviral compounds derived from Nyctanthes arbor-tristis Linn. The virus-suppressing phytochemicals in this plant make it a compelling target for both in vitro and in vivo research in the future.

4.
Cells ; 13(8)2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38667285

RESUMEN

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided.


Asunto(s)
Exosomas , Exosomas/metabolismo , Humanos , Animales , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Enfermedades Vasculares/metabolismo , Enfermedades Vasculares/patología , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades del Sistema Nervioso/patología
5.
Sci Rep ; 14(1): 8902, 2024 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632250

RESUMEN

Colorectal cancer (CRC) is the third most common cancer affecting people. The discovery of new, non-invasive, specific, and sensitive molecular biomarkers for CRC may assist in the diagnosis and support therapeutic decision making. Exosomal miRNAs have been demonstrated in carcinogenesis and CRC development, which makes these miRNAs strong biomarkers for CRC. Deep sequencing allows a robust high-throughput informatics investigation of the types and abundance of exosomal miRNAs. Thus, exosomal miRNAs can be efficiently examined as diagnostic biomarkers for disease screening. In the present study, a number of 660 mature miRNAs were detected in patients diagnosed with CRC at different stages. Of which, 29 miRNAs were differentially expressed in CRC patients compared with healthy controls. Twenty-nine miRNAs with high abundance levels were further selected for subsequent analysis. These miRNAs were either highly up-regulated (e.g., let-7a-5p, let-7c-5p, let-7f-5p, let-7d-3p, miR-423-5p, miR-3184-5p, and miR-584) or down-regulated (e.g., miR-30a-5p, miR-99-5p, miR-150-5p, miR-26-5p and miR-204-5p). These miRNAs influence critical genes in CRC, leading to either tumor growth or suppression. Most of the reported diagnostic exosomal miRNAs were shown to be circulating in blood serum. The latter is a novel miRNA that was found in exosomal profile of blood serum. Some of the predicted target genes of highly expressed miRNAs participate in several cancer pathways, including CRC pathway. These target genes include tumor suppressor genes, oncogenes and DNA repair genes. Main focus was given to multiple critical signaling cross-talking pathways including transforming growth factor ß (TGFß) signaling pathways that are directly linked to CRC. In conclusion, we recommend further analysis in order to experimentally confirm exact relationships between selected differentially expressed miRNAs and their predicted target genes and downstream functional consequences.


Asunto(s)
Neoplasias Colorrectales , Exosomas , MicroARNs , Humanos , MicroARNs/genética , Suero/metabolismo , Neoplasias Colorrectales/patología , Pronóstico , Biomarcadores/metabolismo , Exosomas/metabolismo
6.
J Invertebr Pathol ; 204: 108100, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38561070

RESUMEN

It has long been known that while both the Bacillus thuringiensis pesticidal proteins Cry2Aa and Cry2Ab have wide-ranging activities against lepidopteran insects only the former has activity against the mosquito Aedes aegypti. We have previously shown that this differential specificity is influenced by the N-terminal region of these proteins and here demonstrate that this is due to these sections affecting proteolytic activation. Enzymes from the midgut of A. aegypti cleave Cry2Aa at the C-terminal side of amino acid 49 resulting in a 58 kDa fragment whereas these enzymes do not cleave Cry2Ab at this position. The 58 kDa, but not the protoxin, form of Cry2Aa is capable of interacting with brush border membrane vesicles from A. aegypti.


Asunto(s)
Aedes , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas , Endotoxinas , Proteínas Hemolisinas , Proteolisis , Animales , Endotoxinas/metabolismo , Toxinas de Bacillus thuringiensis/metabolismo , Proteínas Hemolisinas/metabolismo , Proteínas Bacterianas/metabolismo , Control Biológico de Vectores , Bacillus thuringiensis
7.
Biometals ; 37(4): 905-921, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38361146

RESUMEN

Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes [Pd(SCN)2(4-Acpy)2] (1), [Pd(N3)2(4-Acpy)2] (2) [Pd(paOH)2].2Cl (3) and [Pt(SCN)2(paO)2] (4) were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes 1-4 was confirmed using spectroscopic and X-ray crystallography methods. Complexes 1-4 have similar features in isomerism that include the trans coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes 1-4 was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes 1-4 with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC50 of complex 1 was lowest in MCF-7 cells and complex 2 in T47D cells. Complex 4 has the highest effectiveness on HCT116. The selective index (SI) of complexes 1-4 has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex 2 and platinum complex 4 exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes 1-4 and cisplatin could induce p53. All complexes 1-4 elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.


Asunto(s)
Antineoplásicos , Apoptosis , Complejos de Coordinación , Paladio , Piridinas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Paladio/química , Paladio/farmacología , Piridinas/química , Piridinas/farmacología , Apoptosis/efectos de los fármacos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Platino (Metal)/química , Platino (Metal)/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/química , Compuestos Organoplatinos/síntesis química , Cristalografía por Rayos X , Estructura Molecular , Relación Dosis-Respuesta a Droga
8.
Cureus ; 16(1): e52421, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38371120

RESUMEN

BACKGROUND: Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance that develops during pregnancy. It is associated with adverse maternal and fetal outcomes and has long-term health implications for both the mother and the child. This study aimed to estimate the prevalence of adverse pregnancy outcomes in women with and without GDM in the Al-Baha region, Saudi Arabia. METHODS: A cross-sectional study was conducted in the Al-Baha region from April 2023 to November 2023. The study included mothers residing in the Al-Baha region who were willing to participate and had access to a social media account. A simple random sampling technique was used, and the estimated sample size was 422. A self-administered electronic questionnaire was used to collect data on socio-demographic and lifestyle factors, as well as the pregnancy outcomes of diabetic and non-diabetic mothers. Descriptive and inferential statistical analyses were performed using IBM SPSS Statistics for Windows, Version 28.0 (Released 2012; IBM Corp., Armonk, New York, United States). RESULTS: We included 422 women in the study with the majority of participants in the age group of 36-40 years(15.4%, n=74). Most participants (66.6%, n=321) had attained a university degree, and a significant proportion resided in Al-Baha City (52.3%, n=252). Maternal outcomes indicated a significant association between GDM and the development of eclampsia (OR = 8.296, 95%CI: 4.353-15.810, p < 0.001), as well as an increased risk of thyroid diseases (OR = 2.723, 95%CI: 1.428-5.193, p = 0.002). Fetal outcomes revealed a significant association between GDM and respiratory distress/lack of oxygen in newborns (OR = 2.032, 95%CI: 1.085-3.805, p = 0.024), and infants of GDM patients had a higher risk of hypoglycemia (OR = 8.099, 95%CI: 3.350-19.581, p < 0.001). CONCLUSION: We found that GDM increased the risk of complications such as eclampsia, thyroid problems, and postpartum hemorrhage. GDM was also associated with shorter pregnancy durations, higher cesarean section rates, and an increased risk of developing type 2 diabetes post pregnancy. The study emphasized the importance of comprehensive GDM therapy and monitoring.

9.
Cureus ; 16(1): e52057, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38213938

RESUMEN

Background Hepatitis B is a global public health concern. Understanding the awareness, testing practices, and vaccination status of individuals is crucial for effective prevention and control strategies. This study aims to assess these aspects among participants in the Al-Baha region, Saudi Arabia. Methodology A cross-sectional study was conducted among 440 participants. Demographic data, awareness of hepatitis B, knowledge of transmission modes, symptoms, and complications were collected through a structured questionnaire. Participants' testing and screening practices, sources of information, and vaccination status were also assessed. Data were analyzed using descriptive statistics and associations were explored using chi-square tests. Results The majority of participants were females (51.8%) and aged 18-25 years (55.2%). While most participants had heard of hepatitis B (85.7%), only a small percentage correctly identified sexual contact as a mode of transmission (38.6%). Knowledge regarding symptoms and complications was moderate, with 52.3% correctly identifying symptoms and 69.8% recognizing liver damage and cirrhosis as complications. Although awareness of screening was high (84.8%), the actual practice was low (35.0%). Education was the least reported source of information, while the internet (46.7%) and health care provider (27.6%) were commonly mentioned. Approximately half of the participants reported receiving the hepatitis B vaccine (48.9%), but a significant proportion had not completed all vaccine doses (55.0%). Conclusion The study revealed moderate awareness of hepatitis B among the participants, but knowledge gaps existed regarding transmission modes and complete symptom recognition. Testing and screening practices were suboptimal, with low rates of screening despite high awareness. Vaccination uptake was moderate, but incomplete vaccine schedules were prevalent. Targeted educational campaigns are needed to address knowledge gaps, promote testing and completion of vaccination schedules, and enhance the role of healthcare providers in disseminating accurate information. Improving knowledge and practices related to hepatitis B can strengthen public health efforts, enhance prevention, and control strategies.

10.
Cureus ; 16(1): e51454, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38169697

RESUMEN

Cavernoma, also called a cavernous malformation, is a vascular malformation that happens during development. It tends to look like a berry-shaped lesion. In cerebral hemorrhagic cavernous malformations (cavernoma), T1-weighted imaging that shows hyperintense perilesional edema in brain masses is an unusual radiological finding. This sign's association with cavernoma is gaining prominence. We present the case of a 35-year-old female patient without significant medical history who reported a seven-day history of left-side weakness that began in the upper limb, progressed to the lower limb, and was associated with nausea. The non-contrast T1- T1-weighted images displayed a gradient of hyperintense content of the lesion with surrounding relatively hyperintense perilesional edema. The patient consequently underwent surgery to evacuate the hematoma and excise the lesion, which went uneventfully.

11.
Crit Pathw Cardiol ; 23(1): 12-16, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37948094

RESUMEN

BACKGROUND: The use of dual antiplatelet therapy (DAPT) after coronary revascularization for left-main disease is still debated. The study aimed to characterize patients who received dual versus single antiplatelet therapy (SAPT) after coronary artery bypass grafting (CABG) for unprotected left-main disease and compare the outcomes of those patients. RESULTS: This multicenter retrospective cohort study included 551 patients who were grouped into 2 groups: patients who received SAPT (n = 150) and those who received DAPT (n = 401). There were no differences in age ( P = 0.451), gender ( P = 0.063), smoking ( P = 0.941), diabetes mellitus ( P = 0.773), history of myocardial infarction ( P = 0.709), chronic kidney disease ( P = 0.615), atrial fibrillation ( P = 0.306), or cerebrovascular accident ( P = 0.550) between patients who received SAPT versus DAPT. DAPTs were more commonly used in patients with acute coronary syndrome [87 (58%) vs. 273 (68.08%); P = 0.027], after off-pump CABG [12 (8%) vs. 73 (18.2%); P = 0.003] and in patients with radial artery grafts [1 (0.67%) vs. 32 (7.98%); P < 0.001]. While SAPTs were more commonly used in patients with low ejection fraction [55 (36.67%) vs. 61 (15.21%); P < 0.001] and in patients with postoperative acute kidney injury [27 (18%) vs. 37 (9.23%); P = 0.004]. The attributed treatment effect of DAPT for follow-up major adverse cerebrovascular and cardiac events was not significantly different from that of SAPT [ß, -2.08 (95% confidence interval (CI), -20.8-16.7); P = 0.828]. The attributed treatment effect of DAPT on follow-up all-cause mortality was not significantly different from that of SAPT [ß, 4.12 (CI, -11.1-19.32); P = 0.595]. There was no difference in bleeding between groups ( P = 0.666). CONCLUSIONS: DAPTs were more commonly used in patients with acute coronary syndrome, after off-pump CABG, and with radial artery grafts. SAPTs were more commonly used in patients with low ejection fraction and acute kidney injury. Patients on DAPT after CABG for left-main disease had comparable major adverse cerebrovascular and cardiac events and survival to patients on SAPT, with no difference in bleeding events.


Asunto(s)
Síndrome Coronario Agudo , Lesión Renal Aguda , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Síndrome Coronario Agudo/cirugía , Síndrome Coronario Agudo/inducido químicamente , Estudios Retrospectivos , Resultado del Tratamiento , Puente de Arteria Coronaria/efectos adversos , Hemorragia/inducido químicamente , Lesión Renal Aguda/inducido químicamente
12.
Cureus ; 15(10): e46422, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37927731

RESUMEN

BACKGROUND: A common form of forefoot deformity, hallux valgus (HV) is characterized by a prominent first metatarsal head, lateral deviation of the hallux, and medial deviation of the first metatarsal bone. In the case of HV, corrective osteotomies are performed with good results and patient satisfaction. METHODS: A retrospective cohort study of patients who underwent corrective osteotomy for hallux valgus from 2016 to 2022 was conducted at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Data were collected by chart review using the BestCARE system. IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, New York, United States) was used for statistical analysis. RESULTS: Our study included 166 patients. The mean age of the patients was found to be 41.3 years old and about 152 (91.6%) of them were females. The most frequently reported comorbidity was hypertension (10.2%). The mean hallux valgus angle was found to be 36.1 ± 9.9 and the mean intermetatarsal angle was found to be 15 ± 4.4 degrees. Seventy-six (45.8%) patients underwent nonoperative management first. The mean age at diagnosis among males was found to be 28.5 ± 11.3 years and among females was 37.9 ± 14.4 years; a significant difference between means was noted (p-value = 0.019) with mean age at diagnosis in males being significantly lesser than in females. CONCLUSION: Significant improvement and reduction were seen in HV angle post surgery. Nearly half of the patients underwent nonoperative management first. Age at diagnosis is significantly younger in males compared to females.

13.
Cureus ; 15(10): e46991, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38022308

RESUMEN

Background This study aims to investigate and report the outcomes of various management modalities used for hallux rigidus, a common form of degenerative joint disease affecting the foot and ankle. The research focuses on understanding the pathophysiology, classification systems, and nonoperative approaches such as medical therapy, intra-articular injections, shoe modifications, and physical therapy. Surgical techniques, including joint-sparing and joint-sacrificing procedures, are explored, considering factors such as disease stage and patient preferences. Methods A retrospective cohort study was conducted at King Abdulaziz Medical City (KAMC), Riyadh. The study included all patients who were diagnosed with hallux rigidus from the period 2016 to 2022. Data were collected through the BESTCare system at KAMC. All the data were collected through Microsoft Excel (Microsoft Corporation, Redmond, Washington) and transferred for analysis. Statistical analysis was performed using the IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York). Frequencies and percentages were used to detail categorical variables, whereas continuous variables were examined by the mean and standard deviation. A p-value of <0.05 was considered to report the statistical significance. Results A total of 84 patients were included. The majority were women (60.7%). Diabetes and hypertension were prevalent comorbidities, affecting 21.4% and 35.7% of patients, respectively. Nonoperative management was the most common approach (66.7%). Complications were minimal (2.4% infections, 1.2% metatarsalgia), and 67.9% of patients reported no persistence of symptoms after treatment. Conclusion The low complication rates and the lack of significant associations between treatment modalities and outcomes suggest the generally safe and effective nature of the employed interventions. These findings can guide clinicians in making informed decisions regarding the management of hallux rigidus, while also highlighting areas for further research to improve treatment strategies and outcomes.

14.
J Biomol Struct Dyn ; : 1-16, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37668009

RESUMEN

The chikungunya (CHIK) virus is an arbovirus belonging to the alphavirus (Togaviridae family). Around 85% of infected individuals suffer from symptoms such as high fever and severe joint pain; about 30 to 40% will develop a chronic joint illness. The Nsp4 protease is the most conserved protein in the alphavirus family and serves as an RNA-dependent RNA polymerase (RdRp). Targeting this enzyme might inhibit the CHIKV replication cycle. This work aims to in silico study the CHIKV RdRp inhibitory effect of peptides derived from camel milk protein as antiviral peptides. Various bioinformatics tools were recruited to identify, screen, predict and assess peptides obtained from camel milk as antiviral peptides (AVPs). During this study, CHIKV Nsp4 (polymerase) was used as a target to be inhibited by interaction with peptides derived from camel milk protein. Among 91 putative bioactive peptides, the best predicted 5 were further evaluated. Molecular docking showed that the top 5 AVPs generated better docking scores and interacted well with active sites of Nsp4 by the formation of different hydrogen bonds as well as other bonds. AVP63 and AVP20 showed the best Molecular docking and MD simulation results. The residue 315ASP of the GDD motif (catalytic core) exhibited a favorable interaction with the AVPs. The findings of this study suggest that the AVP20 derived from camel milk protein can be a potential novel CHIKV polymerase inhibitor.Communicated by Ramaswamy H. Sarma.

15.
Cureus ; 15(8): e44241, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37645664

RESUMEN

Objectives To study the association between the level of knowledge regarding professionalism and demographic characteristics among medical students from years three to five at King Saud University, Riyadh, Saudi Arabia. Methods Data for this quantitative observational cross-sectional study were collected using stratified random sampling. The participants included male and female students from years three to five studying at the College of Medicine, King Saud University. Data were collected using a self-administered questionnaire and analyzed using the Student's t-test and a one-way ANOVA test. Results The study comprised 112 female (52%) and 103 male (48%) students who completed 215 questionnaires. The mean percentage values of correct answers by females and males were 59.99% and 59.31%, respectively. Statistical analysis revealed no significant difference between the mean percentage of correct answers given by males and females (p=0.684). The mean percentage of correct answers among the 3rd, 4th, and 5th-year medical students was 59.27%, 56.56%, and 62.72%, respectively. Statistical analysis revealed significant differences between the academic year groups (p<0.05), and the grade point average (GPA) groups showed significant differences (p<0.05). Conclusion A highly significant association was found between knowledge of professionalism and both academic level and performance among medical students. This suggests that professional perception evolves parallel to acquiring basic science and clinical knowledge.

16.
J Biomol Struct Dyn ; : 1-14, 2023 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-37480259

RESUMEN

Morganella morganii is a Gram-negative bacterial pathogen that causes bacteremia, urinary tract infections, intra-abdominal infections, chorioamnionitis, neonatal sepsis, and newborn meningitis. To control this bacterial pathogen a total of 3565 putative proteins targets in Morganella morganii were screened using comparative subtractive analysis of biochemical pathways annotated by the KEGG that did not share any similarities with human proteins. One of the targets, D-alanyl-D-alanine carboxypeptidase DacB [Morganella] was observed to be implicated in the majority of cell wall synthesis pathways, leading to its selection as a novel pharmacological target. The drug that interacted optimally with the identified target was observed to be Cefoperazone (DB01329) with the estimated free energy of binding -8.9 Kcal/mol. During molecular dynamics simulations; it was observed that DB01328-2exb and DB01329-2exb complexes showed similar values as the control FMX-2exb complex near 0.2 nm with better stability. Furthermore, MMPBSA total free energy calculation showed better binding energy than the control complex for DB01329-2exb interaction i.e. -31.50 (±0.93) kcal/mol. Our presented research suggested that D-alanyl-D-alanine carboxypeptidase DacB could be a therapeutic target and cefoperazone could be a promising ligand to inhibit the D-alanyl-D-alanine carboxypeptidase DacB protein of Morganella morganii. To identify prospective therapeutic and vaccine targets in Morganella morganii, this is the first computational and subtractive genomics investigation of various metabolic pathways exploring other therapeutic targets of Morganella morganii. In vitro/in vivo experimental validation of the identified target D-alanyl-D-alanine carboxypeptidase and the design of its inhibitors is suggested to figure out the best dose, the drug's effectiveness, and its toxicity.Communicated by Ramaswamy H. Sarma.

17.
J Med Life ; 16(5): 773-781, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37520474

RESUMEN

Cervical cancer is a significant cause of female mortality worldwide, and early detection through regular screening is crucial for reducing mortality rates. However, in developing countries, the uptake of Pap smear tests (PST) is low, mostly due to cultural and social factors and a lack of knowledge. This cross-sectional study assessed knowledge, attitude, and practice of cervical cancer screening among practitioners working at primary healthcare centers in Saudi Arabia. Furthermore, the study aimed to identify the potential barriers that prevent female physicians from performing cervical cancer screening tests. A self-administrated, well-structured questionnaire was used to survey 95 female physicians, including residents, specialists, and consultants in several primary health care centers (PHCCs) in Jeddah managed by the Ministry of Health during September 2019. The results showed that 80% of participants knew about cervical cancer, and 97.8% were aware that PST is a screening tool. However, only 47% advised female patients to get tested for cervical cancer. The factors identified as barriers to test uptake included asymptomatic females (34%), lack of time on the part of the practitioner (24%), and a lack of evidence for risk factors (23%). Additionally, only 42.2% of the participating physicians had undergone a Pap smear test themselves. The study highlights the need for further research to assess HPV status in the population and explore the correlation between circumcision and cervical cancer, as well as polygamy and cervical cancer. The findings suggest that while a good level of knowledge about cervical cancer exists, there is a need to improve compliance with cervical cancer screening guidelines among female physicians in Saudi Arabia.

18.
Cureus ; 15(5): e39589, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37384092

RESUMEN

Background Gastric cancer is a significant health concern worldwide, and its incidence varies across different populations. This study aimed to assess the level of knowledge and awareness of gastric cancer among the general population in Al-Baha City, Saudi Arabia.  Methodology This is a cross-sectional study that was conducted among the residents of Al-Baha city older than 18 years. The study was conducted based on a questionnaire that has been developed by a previous study. Data were initially recorded in an Excel sheet before being exported to the SPSS program, version 25 for data analysis. Results The survey included 426 respondents from Al-Baha city, Saudi Arabia, with 56.8% being females and the majority being in the age groups (21-30 years). Alcohol consumption (mean=4.5, SD= 0.77), smoking cigarettes or Shisha (mean= 4.38, SD=0.852), family history of gastric cancer (mean= 4, SD=1.008), a past medical history of gastric cancer (mean= 3.99, SD=0.911), stomach ulcer (mean=3.76, SD=0.898), and consumption of smoked food (mean= 3.69, SD=0.956) are the most widely recognized risk factors. The most highly recognized symptoms are gastrointestinal bleeding (mean= 4.03, SD=0.875), abdominal lump (mean= 3.94, SD=0.926), weight loss (mean= 3.93, SD=0.963), recurrent nausea and vomiting (mean=3.76, SD=0.956), and abdominal pain (mean= 3.57, SD=0.995). The study also identified several subgroups of the population that may benefit from targeted educational programs, including individuals in the age group of 41-50 years and those in non-medical occupations. Conclusion The study found that participants had a moderate level of knowledge about the risk factors and symptoms of gastric cancer, with significant variability among different subgroups of the population. Further research is needed to investigate the prevalence and risk factors of gastric cancer in Saudi Arabia and other similar populations, to develop effective prevention and management strategies for this disease.

19.
Cureus ; 15(5): e38503, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37273406

RESUMEN

Bone defects are severe conditions caused by various etiologies, including trauma, tumor resection, or chronic osteomyelitis. Different surgical interventions can be utilized to manage such cases, including autologous graft or allograft implantation, distraction osteogenesis, acute shortening, amputation, or the induced membrane technique. Herein, the case of a 39-year-old woman with complex bilateral distal femoral fractures with intra-articular extension is presented. The fractures were accompanied by a significant metaphyseal bone defect, which was managed successfully using the induced membrane Masquelet technique. The patient fully healed despite residual knee joint contractures that did not inhibit her mobility. In conclusion, the Masquelet technique successfully manages complex bone defects and restores functionality even in bilateral simultaneous open bone defects.

20.
Biomolecules ; 13(5)2023 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-37238708

RESUMEN

Plant cells release tiny membranous vesicles called extracellular vesicles (EVs), which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. These plant-derived EVs (PDEVs) are safe and easily extractable and have been shown to have therapeutic effects against inflammation, cancer, bacteria, and aging. They have shown promise in preventing or treating colitis, cancer, alcoholic liver disease, and even COVID-19. PDEVs can also be used as natural carriers for small-molecule drugs and nucleic acids through various administration routes such as oral, transdermal, or injection. The unique advantages of PDEVs make them highly competitive in clinical applications and preventive healthcare products in the future. This review covers the latest methods for isolating and characterizing PDEVs, their applications in disease prevention and treatment, and their potential as a new drug carrier, with special attention to their commercial viability and toxicological profile, as the future of nanomedicine therapeutics. This review champions the formation of a new task force specializing in PDEVs to address a global need for rigor and standardization in PDEV research.


Asunto(s)
COVID-19 , Vesículas Extracelulares , Neoplasias , Humanos , COVID-19/metabolismo , Vesículas Extracelulares/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/metabolismo , Neoplasias/metabolismo
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