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1.
Medicina (Kaunas) ; 60(8)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39202627

RESUMEN

Background and Objectives: Ventilator-associated pneumonia (VAP) is a common complication in critically ill patients receiving mechanical ventilation. The incidence rates of VAP vary, and it poses significant challenges due to microbial resistance and the potential for adverse outcomes. This study aims to explore the microbial profile of VAP and evaluate the utility of biomarkers and illness severity scores in predicting survival. Materials and Methods: A retrospective cohort study was conducted involving 130 patients diagnosed with VAP. Microbial analysis of bronchoalveolar lavage (BAL) fluid, as well as measurements of C-reactive protein (CRP) and procalcitonin (PCT) levels, were performed. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated to assess illness severity. Statistical analyses were conducted to determine correlations and associations. Results: The study revealed that Klebsiella pneumoniae (K. pneumoniae) (50.7%) and Pseudomonas aeruginosa (P. aeruginosa) (27.69%) were the most identified microorganisms in VAP cases. SOFA (p-value < 0.0001) and APACHE II (p-value < 0.0001) scores were effective in assessing the severity of illness and predicting mortality in VAP patients. Additionally, our investigation highlighted the prognostic potential of CRP levels (odds ratio [OR]: 0.980, 95% confidence interval [CI] 0.968 to 0.992, p = 0.001). Elevated levels of CRP were associated with reduced survival probabilities in VAP patients. Conclusion: This study highlights the microbial profile of VAP and the importance of biomarkers and illness severity scores in predicting survival. Conclusions: The findings emphasize the need for appropriate management strategies to combat microbial resistance and improve outcomes in VAP patients.


Asunto(s)
APACHE , Biomarcadores , Proteína C-Reactiva , Neumonía Asociada al Ventilador , Humanos , Neumonía Asociada al Ventilador/microbiología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Biomarcadores/análisis , Anciano , Proteína C-Reactiva/análisis , Adulto , Polipéptido alfa Relacionado con Calcitonina/sangre , Polipéptido alfa Relacionado con Calcitonina/análisis , Puntuaciones en la Disfunción de Órganos , Pseudomonas aeruginosa/aislamiento & purificación , Líquido del Lavado Bronquioalveolar/microbiología , Líquido del Lavado Bronquioalveolar/química , Estudios de Cohortes , Respiración Artificial/efectos adversos , Índice de Severidad de la Enfermedad
2.
Pharmaceuticals (Basel) ; 17(8)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39204109

RESUMEN

The aim of this study was to assess L-carnitine's effects on adult male rats' lung damage brought on by amiodarone, which is a potent antiarrhythmic with limited clinical efficacy due to potentially life-threatening amiodarone-induced lung damage. Because of the resemblance among the structural abnormalities in rats' lungs that follows amiodarone medication and pulmonary toxicity in human beings, this animal model may be an appropriate example for this disease entity. Amiodarone produced pulmonary toxicity in twenty-four healthy male albino rats (150-180 g) over a period of 6 weeks. Four groups of six rats each were established: control, sham, amiodarone, and L-carnitine plus amiodarone. Histological, ultrastructural, oxidative stress, and inflammatory markers were determined during a 6-week exposure experiment. Amiodarone-induced lung damage in rats may be brought on due to oxidative stress producing significant pulmonary cytotoxicity, as evidenced by the disruption of the mitochondrial structure, severe fibrosis, and inflammatory response of the lung tissue. Lungs already exposed to such harmful effects may be partially protected by the antioxidant L-carnitine. Biochemical markers of lung damage brought on by amiodarone include lung tissue levels of the enzyme's catalase, superoxide dismutase, and reduced glutathione. The levels of lipid peroxides in lung tissue measured as malondialdehyde increased significantly upon exposure to amiodarone. In addition, the levels of tumor necrosis factor alpha were significantly elevated in response to amiodarone. The effect of L-carnitine on amiodarone-induced pulmonary toxicity was studied in rats. It is interesting to note that the intake of L-carnitine in rats treated with amiodarone partially restored the biochemical and histopathological alterations brought on by amiodarone to their original levels. Tumor necrosis factor alpha levels were significantly reduced upon L-carnitine exposure. These results suggest that L-carnitine can be used to treat amiodarone-induced pulmonary dysfunction.

3.
Medicine (Baltimore) ; 103(29): e38868, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39029074

RESUMEN

Depression is a common comorbidity in children and adolescents with type 1 diabetes mellitus (T1DM), yet its prevalence, impact, and intervention strategies remain underexplored. This study aims to assess the prevalence of depression among children and adolescents with T1DM, investigate its impact on health outcomes, and explore potential intervention strategies. A convenient sampling method was employed to recruit 229 participants aged 6 to 18 years from a single center. Data collection involved validated assessments, demographic surveys, and diabetes-related factor examinations during routine clinic visits. The patient health questionnaire-9 was utilized to evaluate the severity of depressive symptoms. Associations between depression and sociodemographic variables, diabetes management factors, and health behaviors were analyzed using chi-squared tests and logistic regression analysis. The prevalence of depression among participants was 43.23%. Older age, lower parental education levels, lower household income, smoking, and comorbidities were identified as significant risk factors for depression. Associations were found between depression and diabetes management factors, including glycemic control and frequency of glucose monitoring. Depression is highly prevalent among children and adolescents with T1DM and is associated with sociodemographic factors, health behaviors, and diabetes management. Integrated approaches to care that address both physical and mental health aspects are crucial for improving outcomes in this population.


Asunto(s)
Depresión , Diabetes Mellitus Tipo 1 , Humanos , Adolescente , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Masculino , Niño , Femenino , Depresión/epidemiología , Depresión/etiología , Prevalencia , Comorbilidad , Factores de Riesgo , Estudios Transversales , Conductas Relacionadas con la Salud , Factores Socioeconómicos
4.
Mol Cell Endocrinol ; 591: 112280, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38797354

RESUMEN

Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 106 cells/rat doses. A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index). Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways.


Asunto(s)
Apoptosis , Biomarcadores , Diabetes Mellitus Experimental , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Transducción de Señal , Animales , Masculino , Ratas , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Regulación hacia Abajo , Lesiones Cardíacas/metabolismo , Lesiones Cardíacas/etiología , Janus Quinasa 2/metabolismo , Quinasas Janus/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas Wistar , Factores de Transcripción STAT/metabolismo , Factor de Transcripción STAT3/metabolismo
5.
Heliyon ; 10(5): e27164, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38468941

RESUMEN

Currently, doxorubicin (DOX) is one of the medications commonly used in chemotherapy to treat different types of tumors.Nonetheless, despite being effective in multiple tumors, yet its use is limited owing to its cytotoxic effects, the therapeutic use of DOX has been limited. This work aimed to explore whether curcumin (CMN) can prevents DOX-induced cardiotoxicity in rats. Four groups of rats were created, with the first functioning as a control, while the second group received CMN. DOX alone was administered to the third group, whereas CMN and DOX were administered to the fourth group. Lipid peroxidation assessed as Malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), oxidative stress markers as catalase (CAT), superoxide dismutase (SOD), and inflammatory markers as tumor necrosis factor-alpha (TNF-α) in heart homogenates, each one was assessed. Heart specimens was investigated histologically and ultrastructurally. Increased, AST, and ALT serum levels, increased MDA levels, decreased SOD and CAT levels, and increased TNF-α concentrations in heart homogenates were all signs of DOX-induced myocardial injury. Histological and ultrastructural examinations revealed vacuoles and larger, swollen mitochondria in the cytoplasm. Furthermore, DOX caused significant changes in the myocardium, most notably nuclei disintegration, myofibrillar loss, and myocyte vacuolization. Using CMN with DOX reduced the harmful consequences of DOX on the myocardium by returning the increased AST and ALT levels to their original levels as compared to the control and reducing them. In cardiac tissue, CMN significantly increased the concentrations of SOD and CAT and significantly decreased the concentrations of MDA and TNF-α. Biochemical and histological studies have demonstrated that CMN has a heart-protective effect that might be related to its antioxidant and anti-inflammatory capabilities.

6.
J Biomol Struct Dyn ; : 1-18, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38321911

RESUMEN

Dwarfism is a medical term used to describe individuals with a height-vertex measurement that falls below two standard deviations (-2SD) or the third percentile for their gender and age. Normal development of growth is a complicated dynamic procedure that depends upon the coordination of different aspects involving diet, genetics, and biological aspects like hormones in equilibrium. Any severe or acute pathologic procedure may disturb the individual's normal rate of growth. In this research, we examined four (A-D) Pakistani consanguineous families that exhibited syndromic dwarfism, which was inherited in an autosomal recessive pattern. The genomic DNA of each family member was extracted by using phenol-chloroform and Kit methods. Whole Exome Sequencing (WES) of affected family members (IV-11, III-5, IV-4 and III-13) from each group was performed at the Department of Medical Genetics, University of Antwerp, Belgium. After filtering the exome data, the mutations in PPM1F, FGFR3, ERCC2, and PCNT genes were determined by Sanger sequencing of each gene by using specific primers. Afterward, FGFR3 was found to be a suitable drug target among all the mutations to treat achondroplasia also known as disproportionate dwarfism. BioSolveIT softwares were used to discover the lead active inhibitory molecule against FGFR3. This research will not only provide short knowledge to the concerned pediatricians, researchers, and family physicians for the preliminary assessment and management of the disorder but also provide a lead inhibitor for the treatment of disproportionate dwarfism.Communicated by Ramaswamy H. Sarma.

7.
Pharmaceuticals (Basel) ; 17(2)2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38399367

RESUMEN

Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4's genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4's connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4's carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy.

8.
Technol Health Care ; 32(2): 1159-1176, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37599551

RESUMEN

BACKGROUND: Concerns about the harmful effects of smartphone use on teenage development have been raised as the use of cell phones among adolescents has risen. OBJECTIVE: This study aimed to examine the associations of smartphone usage patterns with Body Image Distortion (BID) and weight loss behaviors among adolescent smartphone users in Saudi Arabia. METHODS: This population-based, cross-sectional study was conducted from July to October 2022. We assessed the mean daily length of smartphone use and classified it into quartiles using data from a self-reported survey and data on weekday and weekend use. Self-reported body weight and height were collected via an online survey. Out of the 11384 adolescents, the majority was females (65.7%) and was secondary school students (68.9%). RESULTS: The prolonged smartphone use (301 min/d) was found in 36.4% of adolescents, 181-300 min/d in 27.6% of respondents, 121-180 min/d in 22.4% of respondents, while the modest smartphone use (1-120 min/d) was found only in 13.6% of participants. The duration of smartphone use was significantly associated with BID (P= 0.000); students with middle perceived stress levels (51.4%) and no depressive symptoms (68.9%) used smartphones 121-180 min/d sparingly. However, prolonged smartphone use was significantly associated with the presence of depressive symptoms (42.6%) and high perceived stress levels (21.5%). Weight loss behaviors were significantly associated with smartphone use duration. Modest smartphone use was significantly found in students with normal weight (P= 0.00, 71.9%); however, aerobic physical activity weight loss strategy (P= 0.00, 30.9%) was correlated with prolonged smartphone use. CONCLUSION: Adequate parental advice is required to assist teenagers in developing healthy smartphone usage practices. Digital platform companies may increase their social responsibility for the information generated and delivered on their networks, boosting its beneficial effect.


Asunto(s)
Imagen Corporal , Teléfono Inteligente , Femenino , Humanos , Adolescente , Arabia Saudita , Estudios Transversales , Pérdida de Peso
9.
Mol Genet Genomic Med ; 12(1): e2314, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37937857

RESUMEN

BACKGROUND: Alström syndrome (AS) represents an exceptionally rare genetic disorder characterized by a constellation of features including cardiomyopathy, progressive hearing and vision impairment, as well as obesity. This study seeks to elucidate the genetic underpinnings of this syndrome within the Saudi Arabian population. METHODS: Employing an extended family cohort, we conducted an exhaustive molecular genetic assessment to delineate the presence of Alström syndrome. Additionally, we conducted an extensive review of existing literature from Saudi population to contextualize our findings within the broader understanding of the disorder in our country. RESULTS: Within our studied extended family, we identified two individuals harboring the homozygous pathogenic mutation (c.2729C>G) in the ALMS1 gene [NM_015120.4:c.2729C>G (p.Ser910*)]. Notably, carrier status was observed in the parents, whereas some siblings exhibited typical alleles while others were carriers of the mutation. Intriguingly, a review of the literature unveiled six distinct reports documenting a total of 20 Alström syndrome patients within the Saudi Arabian population, each presenting with distinct novel mutations. CONCLUSIONS: In cases featuring cardiomyopathy, obesity, and progressive hearing and vision loss, Alström syndrome merits inclusion within the differential diagnosis. To confirm the diagnosis, molecular genetic assessment of the ALMS1 gene is imperative, offering definitive clarity amidst the complex clinical presentation. This investigation reinforces the importance of genetic scrutiny for precise diagnosis and highlights the unique genetic landscape of Alström syndrome within the Saudi Arabian population.


Asunto(s)
Síndrome de Alstrom , Cardiomiopatías , Humanos , Síndrome de Alstrom/genética , Síndrome de Alstrom/diagnóstico , Proteínas de Ciclo Celular/genética , Familia Extendida , Arabia Saudita , Obesidad , Mutación
10.
Int J Gen Med ; 16: 4515-4524, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37814640

RESUMEN

Background: Traditional medicine has potential benefits, but distinguishing safe from risky procedures is crucial for safeguarding children's health. Harmful practices in Aseer Region of Saudi Arabia, deeply rooted in cultural heritage, require scrutiny of parental attitudes and awareness. Aim: The study aims to investigate and analyze the awareness, attitudes, and associated factors contributing to Harmful Traditional Medical Practices towards children in Aseer Region of Saudi Arabia. Methodology: This study employed a cross-sectional design, using an online survey to collect data via a structured questionnaire developed from an extensive literature review on harmful traditional child medical practices in Aseer Region of Saudi Arabia. Results: The study found that most respondents were aged 41-49 years (42.4%), lived in cities (77%), had at least an undergraduate degree (50.1%), and favored traditional medicine (55.9%). Common traditional medicine choices included "Herbs" (28.4%) and "Belly massage" (27.6%). Age significantly affected treatment preferences, while "Place of Resident" and "Education Level" hinted at potential differences. Personal experiences (37.2%) and family networks (31.4%) were key sources of information. Logistic regression analysis uncovered intricate links between sociodemographic and traditional medicine practices. Respondents' views on "Awareness", "Effectiveness", and "Complications" demonstrated notable statistical significance, influencing parents' and caregivers' perspectives in the study. Conclusion: The study's outcomes underscore the imperative for heightened awareness and education concerning the potential hazards and complications tied to harmful traditional medical practices among parents and caregivers in Aseer Region of Saudi Arabia, particularly with regard to their children's well-being. The evident inclination towards traditional medicine, reliance on personal experiences and familial networks for healthcare insights, and reservations regarding contemporary medical approaches underline the significance of addressing cultural beliefs.

11.
Children (Basel) ; 10(10)2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37892347

RESUMEN

BACKGROUND: Primary ciliary dyskinesia (PCD, MIM 244400) is an inherited ciliopathy disorder characterized by recurrent sinopulmonary infections, subfertility, and laterality defects. The true incidence of PCD in Saudi Arabia is not known, but it is likely underdiagnosed due to the high prevalence of consanguineous marriages. In this study, we aim to study the clinical and genetic characteristics of PCD patients in the southwestern region of Saudi Arabia to provide guidance to clinicians and researchers studying PCD. METHODS: This was a cross-sectional study conducted between 2019 and 2023 in Abha Maternity and Children's Hospital. Twenty-eight patients with clinically diagnosed PCD were recruited. The diagnosis of PCD was confirmed via whole-exome sequencing. RESULTS: A total of 28 patients from 20 families were identified and recruited for this study. The median age of patients was 7.5 years (IQR = 3, 13 years). The people of different sexes were evenly distributed, and 18 patients (64%) had neonatal respiratory distress (NRD). The median age of diagnosis was 5.5 years (IQR = 2, 11 years), while the age when the first symptoms appeared was 3 months old (IQR = 1, 6 months). The prevalence of a chronic wet cough, chronic rhinosinusitis, ear infections were 100% (n = 28), 78.6% (n = 22), and 67.9% (19), respectively. The most common gene in our study was DNAH5, which represented 17.9% (five out of twenty-eight) of the cases. Furthermore, the remaining pathogenic variants included: 14.3% with RSPH9 in four individuals (three families), 14.3% with DNAI2 in four individuals (two families), and 10.7% with LRRC56 in three individuals (one family). The most common findings on the chest CT scans were consolidation (seen in all patients), mucus plugging (seen in 95%), and bronchiectasis (seen in 77%). In the patients with bronchiectasis, the most commonly affected lobes were the right lower lobe (88%) and left lower lobe (76%). The patients with PCD and situs inversus were more likely to experience NRD than the patients with PCD and situs solitus. The median PICADAR score in the patients with PCD and situs inversus (median: 11.5; Q1: 10-Q3: 12.5) was significantly higher compared to those with PCD and situs solitus (median: 7.5; Q1: 5.8-Q3: 8) (U = 10.5; p < 0.001). CONCLUSION: This study provides preliminary data on the clinical and genetic characteristics of PCD patients in the southwestern region of Saudi Arabia. We found that DNAH5 and RSPH9 genes were the most common genes among the studied population. Furthermore, PCD should be considered for each child with early NRD and laterality defects, and further confirmatory tests are recommended. These findings also highlight the need for greater awareness of the disease in daily clinical practice to facilitate early diagnosis and avoid irreversible lung damage.

12.
Trop Biomed ; 40(3): 337-343, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37897167

RESUMEN

Antibody cross-reactivity among flaviviruses is a major limitation in understanding the prevalence without vector control measures. In this study, we investigated the presence of Zika virus (ZIKV)-specific antibodies and the significance of their cross-reactivity with other flaviviruses, which could affect the serological specificity in both symptomatic and asymptomatic pregnant women. Among the results obtained from 217 serum samples tested for ZIKV-specific IgM and IgG, no specific predictions regarding seropositivity or exposure due to extensive cross-reactivity with dengue virus (DENV) serology could be made. Clear-cut positivity was observed in 1.8% (n = 4) and 1.0% (n = 2) for ZIKV IgM and IgG, respectively. The same samples assessed for DENV showed 1.3% (n = 3) seropositivity each for IgM and IgG levels. None of the samples were positive for ZIKV and DENV IgM or IgG. However, one sample (0.4%) tested positive for ZIKV and DENV IgM. No significant correlation was observed between DENV IgM and IgG when comparing the overlapped serotiters. On the other hand, the ZIKV IgG-positive sample showed higher serotiters for DENV IgG, indicating cross-reactivity with ZIKV but without statistical significance. Therefore, screening for the incidence of ZIKV becomes particularly challenging in a population where the presence or pre-exposure to DENV is observed. Our observations further suggest that unless flavivirus prevalence is properly addressed, determining the prevalence of ZIKV antibodies, which may be confounded with other uninvestigated flaviviruses, will be complicated.


Asunto(s)
Virus del Dengue , Dengue , Infección por el Virus Zika , Virus Zika , Humanos , Femenino , Embarazo , Infección por el Virus Zika/diagnóstico , Mujeres Embarazadas , Anticuerpos Antivirales , Pruebas Serológicas/métodos , Inmunoglobulina G , Inmunoglobulina M , Reacciones Cruzadas , Dengue/diagnóstico
13.
J Appl Microbiol ; 134(11)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37884451

RESUMEN

AIM: The present study aimed to investigate a novel antifungal compound produced by Streptomyces blastmyceticus S108 strain. Its effectiveness against clinical isolates of Candida species and its synergistic effect with conventional antifungal drugs were assessed, and its molecular mechanism of action was further studied against Candida albicans. METHODS AND RESULTS: A newly isolated strain from Tunisian soil, S. blastmyceticus S108, showed significant antifungal activity against Candida species by well diffusion method. The butanolic extract of S108 strain supernatant exhibited the best anti-Candida activity with a minimal inhibitory concentration (MIC) value of 250 µg ml-1, determined by the microdilution method. The bio-guided purification steps of the butanolic extract were performed by chromatographic techniques. Among the fractions obtained, F13 demonstrated the highest level of activity, displaying a MIC of 31.25 µg ml-1. Gas chromatography-mass spectrometry and electrospray ionization mass spectrometry analyses of this fraction (F13) revealed the glycolipidic nature of the active molecule with a molecular weight of 685.6 m/z. This antifungal metabolite remained stable to physicochemical changes and did not show hemolytic activity even at 4MIC corresponding to 125 µg ml-1 toward human erythrocytes. Besides, the glycolipid compound was combined with 5-flucytosine and showed a high synergistic effect with a fractional inhibitory concentration index value 0.14 against C. albicans ATCC 10231. This combination resulted in a decrease of MIC values of 5-flucytosine and the glycolipid-like compound by 8- and 64-fold, respectively. The examination of gene expression in treated C. albicans cells by quantitative polymerase chain reaction (qPCR) revealed that the active compound tested alone or in combination with 5-flucytosine blocks the ergosterol biosynthesis pathway by downregulating the expression of ERG1, ERG3, ERG5, ERG11, and ERG25 genes. CONCLUSION AND IMPACT OF THE STUDY: The new glycolipid-like compound, produced by Streptomyces S108 isolate, could be a promising drug for medical use against pathogenic Candida isolates.


Asunto(s)
Antifúngicos , Streptomyces , Humanos , Antifúngicos/química , Flucitosina/farmacología , Candida , Streptomyces/genética , Candida albicans , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/farmacología
14.
Antibiotics (Basel) ; 12(9)2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37760761

RESUMEN

Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound's structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 µg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets.

15.
Biomedicines ; 11(8)2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37626750

RESUMEN

Cyclin dependent kinase inhibitor 2A (CDKN2A) is a well-known tumor suppressor gene as it functions as a cell cycle regulator. While several reports correlate the malfunction of CDKN2A with the initiation and progression of several types of human tumors, there is a lack of a comprehensive study that analyzes the potential effect of CDKN2A genetic alterations on the human immune components and the consequences of that effect on tumor progression and patient survival in a pan-cancer model. The first stage of the current study was the analysis of CDKN2A differential expression in tumor tissues and the corresponding normal ones and correlating that with tumor stage, grade, metastasis, and clinical outcome. Next, a detailed profile of CDKN2A genetic alteration under tumor conditions was described and assessed for its effect on the status of different human immune components. CDKN2A was found to be upregulated in cancerous tissues versus normal ones and that predicted the progression of tumor stage, grade, and metastasis in addition to poor prognosis under different forms of tumors. Additionally, CDKN2A experienced different forms of genetic alteration under tumor conditions, a characteristic that influenced the infiltration and the status of CD8, the chemokine CCL4, and the chemokine receptor CCR6. Collectively, the current study demonstrates the potential employment of CDKN2A genetic alteration as a prognostic and immunological biomarker under several types of human cancers.

16.
Neuroscience ; 529: 73-87, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37572878

RESUMEN

The ventromedial hypothalamic nucleus (VMN) controls glucose counter-regulation, including pituitary growth hormone (GH) secretion. VMN neurons that express the transcription factor steroidogenic factor-1/NR5A1 (SF-1) participate in glucose homeostasis. Research utilized in vivo gene knockdown tools to determine if VMN growth hormone-releasing hormone (Ghrh) regulates hypoglycemic patterns of glucagon, corticosterone, and GH outflow according to sex. Intra-VMN Ghrh siRNA administration blunted hypoglycemic hypercorticosteronemia in each sex, but abolished elevated GH release in males only. Single-cell multiplex qPCR showed that dorsomedial VMN (VMNdm) Ghrh neurons express mRNAs encoding Ghrh, SF-1, and protein markers for glucose-inhibitory (γ-aminobutyric acid) or -stimulatory (nitric oxide; glutamate) neurotransmitters. Hypoglycemia decreased glutamate decarboxylase67 (GAD67) transcripts in male, not female VMNdm Ghrh/SF-1 neurons, a response that was refractory to Ghrh siRNA. Ghrh gene knockdown prevented, in each sex, hypoglycemic down-regulation of Ghrh/SF-1 nerve cell GAD65 transcription. Ghrh siRNA amplified hypoglycemia-associated up-regulation of Ghrh/SF-1 neuron nitric oxide synthase mRNA in male and female, without affecting glutaminase gene expression. Ghrh gene knockdown altered Ghrh/SF-1 neuron estrogen receptor-alpha (ERα) and ER-beta transcripts in hypoglycemic male, not female rats, but up-regulated GPR81 lactate receptor mRNA in both sexes. Outcomes infer that VMNdm Ghrh/SF-1 neurons may be an effector of SF-1 control of counter-regulation, and document Ghrh modulation of hypoglycemic patterns of glucose-regulatory neurotransmitter along with estradiol and lactate receptor gene transcription in these cells. Co-transmission of glucose-inhibitory and -stimulatory neurochemicals of diverse chemical structure, spatial, and temporal profiles may enable VMNdm Ghrh neurons to provide complex dynamic, sex-specific input to the brain glucose-regulatory network.


Asunto(s)
Glucosa , Hipoglucemia , Ratas , Femenino , Masculino , Animales , Glucosa/metabolismo , Núcleo Hipotalámico Ventromedial/metabolismo , Ratas Sprague-Dawley , Glucógeno/metabolismo , Hipoglucemia/metabolismo , Neuronas/metabolismo , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Hipoglucemiantes , ARN Mensajero/metabolismo , Lactatos/metabolismo , ARN Interferente Pequeño/metabolismo
17.
Cell Mol Biol (Noisy-le-grand) ; 69(6): 1-7, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37605598

RESUMEN

In the current scenario, the importance of cardiac biomarkers in diagnosing, assessing, and managing people with cardiovascular discomfort is required. This cross-sectional study examined the relationship between serum leptin and resistin levels among obese people with acute myocardial infarction (AMI) with varying body mass index (BMI). The cardio and diabetic biomarkers among the 77 Saudi patients with hypoxia who lived in the Asir region were analyzed in the study. The patients were categorized into three groups, namely, group 1 (control), group 2 (AMI with normal BMI), and group 3 (AMI with varying BMI). Our results showed a positive correlation between serum glucose, HbA1C, triglycerides, Troponin-I (cTnI), creatine kinase MB (CK-MB), leptin, and resistin in patients with AMI. We also observed significantly lower HbA1C, cholesterol, and insulin values in groups 2 and 3. A statistical difference between the groups with and without AMI and between the genders was noticed. BMI with leptin showed a positive connection in group 3 but no association was observed for groups 1 and 2. A stronger relationship between BMI and leptin levels in men in Group 3 than in women was observed. In all three groups, resistin levels did not correlate with BMI. Thus, circulating leptin concentrations do not significant impact AMI compared to participants with and without AMI. However, resistin levels were considerably higher in obese individuals with AMI. Therefore, we suggest that resistin can be used as a pro-inflammatory marker to detect AMI disorder with varying BMI and as a prognostic marker associated with AMI.


Asunto(s)
Leptina , Infarto del Miocardio , Masculino , Humanos , Femenino , Resistina , Estudios Transversales , Hemoglobina Glucada , Arabia Saudita , Obesidad/complicaciones
18.
Medicine (Baltimore) ; 102(31): e34475, 2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37543809

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has less of an impact among the babies and teenagers, than it does on adults as a whole. Children turned out to be less symptomatic during the coronavirus disease (COVID-19) surge worldwide. Researchers discovered the ways of protection by preemptive care, like, treatment, variants, vaccination, social distancing, and cohorting among children as soon as their medical and epidemiological factors were assessed while being exposed to SARS-CoV-2 transmission. The actual pervasiveness of asymptomatic SARS-CoV-2 contagion is possibly undervalued because of less examination of the asymptomatic children. A half of young-aged people who tested SARS-CoV-2 positive don't show any symptoms as per the study of serology. Nevertheless, there is wide circulation of information reporting a post-infectious acute illness known as multisystem inflammatory syndrome in children (MIS-C) or multisystem hyperinflammatory syndrome. Therefore, we undertook this narrative review to synthesize the evidence from existing studies to assess the relationship between SARS-CoV-2 infections and MIS-C among Children. We reviewed PubMed, Science Direct, and Google Scholar to find the pertinent scientific papers published in English that were available for such analysis. The main purpose of this article is to present, on this limited topic, a better-comprehended review covering pertinent material and data to be informed on SARS-CoV-2 infections and MIS-C among Children.


Asunto(s)
COVID-19 , Lactante , Adolescente , Niño , Humanos , Anciano , COVID-19/diagnóstico , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/terapia , Síndrome
19.
RSC Adv ; 13(33): 23087-23121, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37529365

RESUMEN

Targeted delivery of drug molecules to diseased sites is a great challenge in pharmaceutical and biomedical sciences. Fabrication of drug delivery systems (DDS) to target and/or diagnose sick cells is an effective means to achieve good therapeutic results along with a minimal toxicological impact on healthy cells. Biopolymers are becoming an important class of materials owing to their biodegradability, good compatibility, non-toxicity, non-immunogenicity, and long blood circulation time and high drug loading ratio for both macros as well as micro-sized drug molecules. This review summarizes the recent trends in biopolymer-based DDS, forecasting their broad future clinical applications. Cellulose chitosan, starch, silk fibroins, collagen, albumin, gelatin, alginate, agar, proteins and peptides have shown potential applications in DDS. A range of synthetic techniques have been reported to design the DDS and are discussed in the current study which is being successfully employed in ocular, dental, transdermal and intranasal delivery systems. Different formulations of DDS are also overviewed in this review article along with synthesis techniques employed for designing the DDS. The possibility of these biopolymer applications points to a new route for creating unique DDS with enhanced therapeutic qualities for scaling up creative formulations up to the clinical level.

20.
J Drug Target ; 31(7): 714-724, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37461888

RESUMEN

Bone morphogenetic protein (BMP)-9 is considered a member of the transforming growth factor (TGF)ß superfamily. It was first found as an inducer of bone and cartilage formation and then discovered that this factor mediates several physiologic functions and hemostasis. Besides physiological conditions, BMP9 has also been elucidated that it is involved in several pathological situations, especially cancer. In various cancers, dysregulation of BMP9 has raised the issue that BMP9 might play a conflicting role in tumour development. BMP9 binding to its receptors (BMPRs), including ALKs and BMPRII, induces canonical SMAD-dependent and non-canonical PI3K/AKT and MAPK signalling pathways in tumour cells. BMP9, via inducing apoptosis, inhibiting tumour-promoting cell signalling pathways, suppressing epithelial-mesenchymal transition (EMT) process, blocking angiogenesis, and preventing cross-talk in the tumour microenvironment, mainly exerts tumour-suppressive functions. In contrast, BMP9 triggers tumour-supportive signalling pathways, promotes EMT, and enhances angiogenesis, suggesting that BMP9 is also involved in tumour development. It has been demonstrated that modulating BMP9 expression and functions might be a promising approach to cancer treatment. It has also been indicated that evaluating BMP9 expression in cancers might be a biomarker for predicting cancer prognosis. Overall, BMP9 would provide a promising target in cancer management.


Asunto(s)
Factor 2 de Diferenciación de Crecimiento , Neoplasias , Humanos , Factor 2 de Diferenciación de Crecimiento/metabolismo , Factor 2 de Diferenciación de Crecimiento/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Morfogenéticas Óseas , Transducción de Señal , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Factor de Crecimiento Transformador beta , Microambiente Tumoral
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