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1.
J Family Community Med ; 31(1): 57-62, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38406215

RESUMO

BACKGROUND: The coexistence of coronary artery disease (CAD) and depression is a growing concern, as both conditions lead to disability. Although depression is more prevalent in CAD patients than in the general population and has been associated with adverse cardiac outcomes, the underlying mechanisms linking depression and CAD are not yet fully understood. This study aims to assess the prevalence of depression in postmyocardial infarction (MI) patients as baseline data in Saudi Arabia. MATERIALS AND METHODS: A cross-sectional study was conducted at King Saud Medical City, Riyadh. The study population included male and female patients who had survived MI from January 2022 to June 2022. A sample size of 323 patients was initially planned, but only 249 patients could be included on account of exclusions. The patients underwent screening for depression using Patient Health Questionnaire-2 (PHQ-2), and those who were positive on screening were further assessed using the PHQ-9 according to DSM-5 criteria. Sociodemographic data, comorbidities, and previous cardiac interventions were collected from medical records. RESULTS: The mean age of the study participants was 57.15 years, and majority (76.6%) were males. The prevalence of previously diagnosed depression was 9.2%, and 5.2% of patients reported using antidepressant medication. According to the PHQ-9 scores, 33.33% had depression, 9% had moderate depression, and 2.4% had severe depression. There were significant associations between the severity of depression and previous CAD (P < 0.05), previous coronary artery bypass graft surgery (P < 0.05), and heart failure (P < 0.05). CONCLUSION: This study reveals a high prevalence of depression in post-MI patients at King Saud Medical City. The findings highlight the need for comprehensive management of depression in this population to improve outcomes. Further research into the underlying mechanisms linking depression and CAD to develop effective interventions is required.

2.
Pharmaceuticals (Basel) ; 17(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38399367

RESUMO

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.

3.
J Pers Med ; 13(12)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38138875

RESUMO

Interleukin-1-receptor-associated kinase 4 (IRAK4) possesses a crucial function in the toll-like receptor (TLR) signaling pathway, and the dysfunction of this molecule could lead to various infectious and immune-related diseases in addition to cancers. IRAK4 genetic variants have been linked to various types of diseases. Therefore, we conducted a comprehensive analysis to recognize the missense variants with the most damaging impacts on IRAK4 with the employment of diverse bioinformatics tools to study single-nucleotide polymorphisms' effects on function, stability, secondary structures, and 3D structure. The residues' location on the protein domain and their conservation status were investigated as well. Moreover, docking tools along with structural biology were engaged in analyzing the SNPs' effects on one of the developed IRAK4 inhibitors. By analyzing IRAK4 gene SNPs, the analysis distinguished ten variants as the most detrimental missense variants. All variants were situated in highly conserved positions on an important protein domain. L318S and L318F mutations were linked to changes in IRAK4 secondary structures. Eight SNPs were revealed to have a decreasing effect on the stability of IRAK4 via both I-Mutant 2.0 and Mu-Pro tools, while Mu-Pro tool identified a decreasing effect for the G198E SNP. In addition, detrimental effects on the 3D structure of IRAK4 were also discovered for the selected variants. Molecular modeling studies highlighted the detrimental impact of these identified SNP mutant residues on the druggability of the IRAK4 ATP-binding site towards the known target inhibitor, HG-12-6, as compared to the native protein. The loss of important ligand residue-wise contacts, altered protein global flexibility, increased steric clashes, and even electronic penalties at the ligand-binding site interfaces were all suggested to be associated with SNP models for hampering the HG-12-6 affinity towards IRAK4 target protein. This given model lays the foundation for the better prediction of various disorders relevant to IRAK4 malfunction and sheds light on the impact of deleterious IRAK4 variants on IRAK4 inhibitor efficacy.

4.
Cell ; 186(23): 5114-5134.e27, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37875108

RESUMO

Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with mycobacterial disease from kindreds of different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete deficiency of this translation re-initiation factor impairs the translation of a subset of proteins, including the kinase JAK2 in all cell types tested, including T lymphocytes and phagocytes. JAK2 expression is sufficiently low to impair cellular responses to interleukin-23 (IL-23) and partially IL-12, but not other JAK2-dependent cytokines. Defective responses to IL-23 preferentially impair the production of IFN-γ by innate-like adaptive mucosal-associated invariant T cells (MAIT) and γδ T lymphocytes upon mycobacterial challenge. Surprisingly, the lack of MCTS1-dependent translation re-initiation and ribosome recycling seems to be otherwise physiologically redundant in these patients. These findings suggest that X-linked recessive human MCTS1 deficiency underlies isolated mycobacterial disease by impairing JAK2 translation in innate-like adaptive T lymphocytes, thereby impairing the IL-23-dependent induction of IFN-γ.


Assuntos
Interferon gama , Janus Quinase 2 , Infecções por Mycobacterium , Humanos , Masculino , Proteínas de Ciclo Celular/metabolismo , Interferon gama/imunologia , Interleucina-12 , Interleucina-23 , Janus Quinase 2/metabolismo , Mycobacterium/fisiologia , Infecções por Mycobacterium/imunologia , Infecções por Mycobacterium/metabolismo , Proteínas Oncogênicas/metabolismo
5.
Int. j. morphol ; 41(5): 1513-1526, oct. 2023. ilus
Artigo em Inglês | LILACS | ID: biblio-1521017

RESUMO

SUMMARY: The livers of reptiles are being studied as a model for the link between the environment and hepatic tissue. There have been few investigations on the histology of reptile livers, and very few or no studies have examined the histology of liver of veiled chameleon (Chamaeleo calyptratus). This paper describes the histomorphological, histochemical and ultrastructural characterization of the liver of veiled chameleons in southern Saudi Arabia. Seven Chamaeleo calyptratus were captured in the summer season in Abha City, Aseer region, southern Saudi Arabia. Chamaeleon liver samples were processed for histomorphology, histochemistry and ultrastructure analyses. Morphologically liver of Chamaeleo calyptratus was observed as a large dark brown organ with lighter speckles, which represent melanin deposits. It located at the ventral part of abdominal cavity forward of the stomach. Its dimensions approximately were 3.7 x 2 cm. The liver was a bilobed organ divided into two lobes, right and left lobes. The right one was bigger than the others. The gallbladder was well developed and had an elongated shape, situated between the two lobes and contained the bile for the digestion. Microscopically, the liver was found to be covered by a thick layer of connective tissue, which formed the hepatic capsule. Hepatic parenchyma probably appeared in cross sections as hepatic glandular-like alveoli "acini" or follicular structures with various diameters, each acinus contains approximately four to six hepatocytes, surrounded by sinusoidal capillaries filled with abundant melanomacrophages, which are absent in birds and mammals. Melanomacrophages are common in the hepatic parenchyma's perisinusoidal areas, particularly near portal spaces. Hepatocytes are polyhedral or pyramidal with and mostly contained large, rounded nuclei mostly peripherally located, with prominent dark oval nucleoli. Some of nuclei are eccentric or central position. The cytoplasm appeared spongy or vacuolated and more eosinophilic when stained by hematoxylin-eosin and strongly reactive to PAS staining technique, indicating abundant glycogen content. The reticular fibers that surround hepatocytes, blood arteries, and sinusoids supported the hepatic parenchyma. The blood sinusoids are seen interspersed among hepatocytes of varying sizes. The sinusoidal lumen was bordered by flattened endothelial cells and includes elliptical nucleated erythrocytes and liver macrophages as phagocytes, which are also known as Kupffer cells. Branches of the portal vein, hepatic artery, small bile duct, and lymph vessels were detected in the hepatic portal area "tract" or triad which made up of connective. Hematopoietic tissue was observed in subcapsular region and portal triads. Ultrastructurally, the hepatocyte appeared polyhedric containing a single large rounded basal or eccentric vesicular nucleus with prominent nucleolus. Extensive network of rough endoplasmic reticulum (RER) often arranged in an array parallel to the nuclear membrane with many mitochondria, and Golgi apparatus were described. The cytoplasm contained glycogen granules, vesicles or vacuoles scattered throughout the cytoplasm especially at the apical region were reported. The bile canaliculi and the hepatic "Kupffer" cells were also discussed. This is the first study on the histological characterization of the healthy liver of Yemen veiled chameleon in southern Saudi Arabia. The findings reported here should be used as a reference to compare with the pathological abnormalities of the liver in this animal.


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Assuntos
Animais , Fígado/anatomia & histologia , Lagartos/anatomia & histologia , Fotomicrografia , Hepatócitos , Microscopia Eletrônica de Transmissão , Fígado/ultraestrutura
6.
Drug Deliv ; 30(1): 2183815, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36866455

RESUMO

Human struggle against the deadly disease conditions is continued since ages. The contribution of science and technology in fighting against these diseases cannot be ignored exclusively due to the invention of novel procedure and products, extending their size ranges from micro to nano. Recently nanotechnology has been gaining more consideration for its ability to diagnose and treat different cancers. Different nanoparticles have been used to evade the issues related with conservative anticancer delivery systems, including their nonspecificity, adverse effects and burst release. These nanocarriers including, solid lipid nanoparticles (SLNs), liposomes, nano lipid carriers (NLCs), nano micelles, nanocomposites, polymeric and magnetic nanocarriers, have brought revolutions in antitumor drug delivery. Nanocarriers improved the therapeutic efficacy of anticancer drugs with better accumulation at the specific site with sustained release, improved bioavailability and apoptosis of the cancer cells while bypassing the normal cells. In this review, the cancer targeting techniques and surface modification on nanoparticles are discussed briefly with possible challenges and opportunities. It can be concluded that understanding the role of nanomedicine in tumor treatment is significant, and therefore, the modern progressions in this arena is essential to be considered for a prosperous today and an affluent future of tumor patients.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Micelas , Apoptose , Disponibilidade Biológica
7.
Biotechnol Appl Biochem ; 70(1): 148-156, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35324037

RESUMO

Benzylidene chromanones are small molecules, structurally similar to active phytochemicals. Herein, we report one novel benzylidene chromanone, TMF 104, for its bio-efficacies. Its computational docking for Vanin-1, antioxidant, free radical scavenging capacities, antimicrobial effects, and anticancer efficacy were analyzed. TMF 104 predicated strong binging to Vanin-1 protein with a docking energy of -8.1 kcal/mol. The compound dose-dependently exhibited free-radical scavenging and antioxidant activities when tested in vitro. The compound also had remarkable activity against Salmonella typhimurium, Enterococcus faecalis, Staphylococcus aureus, and Escherichia coli with minimum inhibitory concentration values of 1.5, 2.0, 12.5, and 13.5 µg/ml, respectively. The compound was also effective against Bacillus cereus and Pseudomonas aeruginosa albeit at higher concentrations. TMF 104 dose-dependently inhibited the proliferation of MCF-7, NCI H460, and Caki-1 cells with respective GI50 values of 24.51, 21.95, and 32.95 µg/ml, whereas the compound was toxic to normal Vero cells at much higher concentration of 264.70 µg/ml. The compound also aided in apoptosis and increased the sub G0 /G1 phase of the cell cycle in all three cancer cells tested. Our study identified a novel, potent benzylidene analogue with potent antioxidant, antimicrobial, and anticancer activities, which drives further attention for further research.


Assuntos
Antibacterianos , Anti-Infecciosos , Animais , Chlorocebus aethiops , Antibacterianos/farmacologia , Antibacterianos/química , Antioxidantes/farmacologia , Células Vero , Anti-Infecciosos/farmacologia , Pseudomonas aeruginosa , Testes de Sensibilidade Microbiana
8.
Artigo em Inglês | MEDLINE | ID: mdl-36429701

RESUMO

This record study aimed to investigate the prevalence of metabolic syndrome (MetS) profiles regarding sex, age, and obesity for the riskier factor of cardiovascular diseases in a general population in Saudi Arabia. Laboratory and anthropometric measurements were performed on non-specific participants with variant ages and BMI in either sex. Serobiochemical changes were measured for metabolic profiles, i.e., A1C/FSG, TC, TGC, HDLC/LDLC, Vit.D, TSH/T4, Hb, and Cr. The study was applied in a Polyclinic, Abha, Saudi Arabia in 2020 G. The general population showed variable incidences of MetS profiles, such as 69.4% diabetes, 85.5% hypothyroidism, and 92.2% obesity. Hypothyroidism showed a higher incidence in women rather than in men, but men were more dyslipidemic, with higher TGC and LDLC but low HDLC, compared to women. Men <40 Y. showed diabetes and hypothyroidism, but elders were dyslipidemic. Women <40 Y. showed anemia and hypovitaminosis-D but were suffering from hypothyroidism at all ages. Diabetes, hypothyroidism, hypovitaminosis-D, and dyslipidemia were the main MetS components in both overweight and obese participants, and an incidence of more than 50% in each profile was recorded. Diabetes with hypertension was characteristic of obese participants rather than those overweight. About 66.1% of the mixed-hypercholesterolemic cases were diabetic, but 18.9% of the mixed-diabetic participants were hypercholesterolemic. Castelli's risk factors, CRI-I and CRI-II, and atherogenic indices, AIP and AC, were measured for evaluating the cardiac risk in different populations based on the AUC-ROC and cut-off values. Insulin-resistance marker (TyG) was also measured, showing considerable cut-off values for diabetic susceptibility in the lipidemic participants with higher TGC and TC rather than HDLC or LDLC. In conclusion, MetS showed higher susceptibility to sex and age with increased incidence in women rather than men. However, the cardiac risk was more susceptible to men of higher TGC and low HDLC than women. Type 2 Diabetes mellitus (T2DM) was more prominent in both elders (≥40 Y.) than younger ages of either sex. Anemia and deficiency of Vit. D was characteristic of young women (<40 Y.). Hypothyroidism affects young men <40 Y. but was recorded in women of all ages. Both dyslipidemia and diabetes could trigger CVD, showing higher cardiac risk in mixed-hypercholesterolemic men rather than women. Our study strongly suggests that the consumption of unhealthy junk food, tobacco smoking, lack of exercise, and physical inactivity could be conclusive evidence of MetS in the Saudi population.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Dislipidemias , Hipotireoidismo , Síndrome Metabólica , Masculino , Humanos , Feminino , Idoso , Síndrome Metabólica/epidemiologia , Fatores de Risco Cardiometabólico , Arábia Saudita/epidemiologia , Sobrepeso , Obesidade/epidemiologia , Dislipidemias/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia
9.
Int J Mol Sci ; 23(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36361584

RESUMO

Methotrexate (MTX) is a potent anti-cancer drug, commonly associated with nephrotoxicity via the induction of oxidative stress and apoptosis with alteration of renal water channel proteins, namely aquaporins (AQPs). Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) have shown cytoprotective effects through their anti-oxidant and antiapoptotic activities. The present study aims for the first time to explore the role of LC-PUFA against MTX-induced nephrotoxicity. Rats were divided into the following groups: saline control, LC-PUFA control, MTX, MTX + LC-PUFA (150 mg/kg), or MTX + LC-PUFA (300 mg/kg). Then, H&E staining and immunohistochemical staining for the anti-apoptosis marker B-cell lymphoma 2 (BCL-2), the apoptosis marker BCL2-Associated X Protein (BAX), the proinflammatory marker Nuclear factor kappa B (NF-kB), AQPs 1 and 2 were performed in kidney sections with an assessment of renal oxidative stress. The MTX caused a renal histopathological alteration, upregulated renal BAX and NF-kB, downregulated Bcl-2 and AQP1, altered the distribution of AQP2, and caused oxidative stress. The LC-PUFA attenuated the pathological changes and decreased renal BAX and NF-kB, increased BCL-2 and AQP1, restored the normal distribution of AQP2, and decreased the oxidative stress. Therefore, LC-PUFA is a good adjuvant to MTX to prevent its adverse effects on kidneys through its antiapoptotic, antioxidant, and anti-inflammatory effect and its role in the restoration of the expression of AQPs 1 and 2.


Assuntos
Ácidos Graxos Ômega-3 , Metotrexato , Ratos , Animais , Metotrexato/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , NF-kappa B/metabolismo , Aquaporina 2/metabolismo , Estresse Oxidativo , Rim/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Suplementos Nutricionais
10.
Br J Biomed Sci ; 79: 10150, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35996511

RESUMO

Context: Intermittent short-duration re-oxygenation attenuates cardiac changes in response to hypoxia. Objective: To see if intermittent short-duration re-oxygenation may protect the heart muscle from hypoxia damage. Materials and Methods: Eighteen albino rats were used to carry out the study. Rats divided into: (normoxia); rats exposed to room air as a control, second (hypoxic) group; rats subjected to a pressure of 405 mmHg in a hypobaric chamber to simulate hypoxia at 5,000 m, and third (intermittent short-duration re-oxygenation); rats exposed to room air three times per day. Experiments were all 14 days long. Results: Hypoxia enhanced the oxidative stress biomarker malondialdehyde while lowering the antioxidant superoxide dismutase . The levels of tumour necrosis factor (TNF-α) and interleukin-6 (IL-6) in the myocardium were elevated in hypoxic hearts. The hypoxic rats' cardiac myofibrils showed disarray of muscle fibres, vacuolation of the sarcoplasm, pyknosis of the nucleus, and expansion of intercellular gaps on histological examination. In addition, cardiomyocytes showed degenerative defects in ventricular myocardial cells on ultrastructural analysis. Myofibril thinning and degenerative mitochondrial changes affected intercalated discs with fascia adherent, desmosomes, and gap junction. Intermittent short-duration re-oxygenation improve cardiac histological, ultrastructural and oxidant/antioxidant parameters changes during hypoxia. Conclusion: Hypoxia showed a substantial impact on myocardial architecture, as well as increased oxidative stress and pro-inflammatory cytokines. Intermittent short-duration re-oxygenation significantly decreases hypoxia-induced cardiac changes.


Assuntos
Antioxidantes , Oxidantes , Ratos , Coração/fisiologia , Hipóxia/patologia , Miocárdio/patologia , Fator de Necrose Tumoral alfa , Animais
11.
Healthcare (Basel) ; 9(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34683064

RESUMO

Background: Developmental dysplasia of the hip (DDH) is classified as a group of malformations, varying from abnormal acetabulum (dysplasia) and mild subluxation of the femoral head to fixed displacement (congenital dislocation). This study aimed to assess the knowledge level and its determinants regarding DDH in children among pregnant females in the Aseer region of southwestern Saudi Arabia. Methods: A descriptive cross-sectional study was conducted targeting all pregnant females in the Aseer region between 1 February 2021 and 1 May 2021. A pre-structured online questionnaire was constructed by the researchers to obtain the participating females' bio-demographic data (including age, education status, and obstetric history) and awareness regarding DDH. The last section asked for their source of information regarding DDH. Results: A total of 253 pregnant females (aged between 18 and 45 years; mean age = 30.5 ± 10.2 years) fulfilling the inclusion criteria completed the study questionnaire. About 5% of the females reported having a child with DDH, and 166 (65.6%) pregnant females knew about DDH. Additionally, 110 (43.5%) females reported that they know about how DDH is treated, and 99 (39.1%) knew about DDH complications. The most commonly reported source of information was relatives and friends (44.3%), followed by social media (11.9%) and study and work (7.1%). Conclusions: Pregnant females in the Aseer region have poor knowledge and awareness about DDH and its causes, treatment modalities, and complications. Higher knowledge was associated with either high parity or having a child with DDH.

12.
Libyan J Med ; 16(1): 1918903, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33899704

RESUMO

Dehydration is linked to worse cognitive functions and preference for beverages that are linked to obesity and other health conditions. Saudi Arabia's hot climate can exacerbate these effects and it is important to ensure that children in the region understand the benefits of adequate water intake. To evaluate secondary school student perceptions and practices regarding water intake, investigate how water intake is related to BMI and school performance, and compare international schools to national schools. This cross-sectional study surveyed understanding and practices relating to water intake of national and international secondary school students using a questionnaire based on a random selection of schools and students. One-hundred and sixty-two students from international schools (I) and 157 from national schools (N) responded. Most were aged 16 and 17 years old (I:61.1%, N:76.5%, p = .005). The average BMI of all students was 24.9 ± 6.013 (I:23.6 ± 4.658, N:26.1 ± 6.931, p < 0.001). Students understood beverages do not replace water intake (I:80.2%, N:75.8%, p = .337) and preferred water when thirsty (I:77.8%, N:75.2%, p = .549). However, water consumption was low with more than 50% of students drinking less than 1500 ml a day (I:54.3%, N:70.7%, p = .002). A positive correlation between BMI and water intake was observed only among international school students. Students have inadequate water intake despite understanding the importance of hydration. There are some differences between international school students and national school students that can be attributed to the availability and sources of water, though other factors cannot be excluded.


Assuntos
Índice de Massa Corporal , Ingestão de Líquidos , Instituições Acadêmicas/estatística & dados numéricos , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Desempenho Acadêmico , Adolescente , Estudos Transversais , Desidratação/psicologia , Comportamento de Ingestão de Líquido , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Inquéritos e Questionários
13.
Oncol Lett ; 21(2): 173, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33552290

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common types of primary liver cancer. Despite advancements in the treatment strategies of HCC, there is an urgent requirement to identify and develop novel therapeutic drugs that do not lead to resistance. These novel agents should have the potential to influence the primary mechanisms participating in the pathogenesis of HCC. Heparan sulfate proteoglycans (HSPGs) are major elements of the extracellular matrix that perform structural and signaling functions. HSPGs protect against invasion of tumor cells by preventing cell infiltration and intercellular adhesion. Several enzymes, such as heparanase, matrix metalloproteinase-9 and sulfatase-2, have been reported to affect HSPGs, leading to their degradation and thus enhancing tumor invasion. In addition, some compounds that are produced from the degradation of HSPGs, including glypican-3 and syndecan-1, enhance tumor progression. Thus, the identification of enzymes that affect HSPGs or their degradation products in HCC may lead to the development of novel therapeutic targets. The present review discusses the main enzymes and compounds associated with HSPGs, and their involvement with the pathogenicity of HCC.

14.
Cureus ; 13(12): e20118, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35003961

RESUMO

Urinary tract infection is a common medical condition encountered in outpatient clinics and emergency departments. Recurrence of urinary tract infections is common. The recurrence can arise from behavioral, mechanical, and physiological factors. Urachal anomalies are very rare congenital clinical entities. We present the case of a 41-year-old woman who presented to the emergency department with dysuria, frequency, urgency, and incontinence. There was no history of fever or flank pain. Physical examination revealed no abnormalities. Initial laboratory markers were within the normal range. However, urinalysis findings showed numerous white blood cells and positive leukocyte esterase and nitrite. While these findings are suggestive of acute simple cystitis, the patient had a concerning history of recurrent urinary tract infections. The urology team advised performing an abdominal computed tomography scan to rule out any structural abnormalities. The patient underwent a computed tomography scan, which demonstrated the presence of a fluid-filled structure arising from the dome of the bladder and extending superiorly toward the umbilicus, representing a vesicourachal diverticulum. The patient underwent surgical resection after antibiotic therapy. The vesicourachal diverticulum is a very rare type of urinary tract anomalies. The case highlights the importance of considering congenital urachal anomalies in patients with recurrent urinary tract infections. A computed tomography scan can make the diagnosis of such anomalies with high accuracy.

15.
J Food Biochem ; 44(9): e13346, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32602579

RESUMO

The study aimed to clarify the characteristics of black tea (BTE) and/or curcumin (CMN) against aflatoxin-B1 (AFB1). Forty eight adult male Sprague-Dawley rats were divided into eight groups. G1 was non-treated control. G2, G3, and G4 were olive oil, BTE, and CMN, respectively. G5 was olive oil-dissolved AFB1 (25 µg/kg b.w). G6, G7, and G8 were AFB1 along with BTE (2%), CMN (200 mg/kg b.w.), and BTE plus CMN, respectively. All treatments were orally given for consecutive 90 days. After treatment period, rats were sacrificed. Serobiochemical analysis and histopathology showed hepatorenal dysfunction in response to AFB1. Glutathione-antioxidants were significantly decreased versus increased lipid peroxides (p < .05-.001). AFB1 significantly increased the expression of the antitumor p53, but decreased that of antiapoptotic Bcl2 in liver or kidney tissue, either (p < .05). BTE or CMN ameliorated those changes induced by AFB1 in both liver and kidney with highly pronounced improvement when combined BTE/CMN was used. PRACTICAL APPLICATIONS: Black tea (BTE) and curcumin (CMN) were known for their antioxidant effects, and several studies reported their independent effects against different toxicities including aflatoxicosis. The current study clarifies the ameliorative characteristics of both agents; BTE and/or CMN, against the toxicity resulted from the chronic exposure to aflatoxin-B1 (AFB1) (25 µg/kg b.w. for consecutive 90 days). The dose of either agents, BTE or CMN, was 200 mg/kg b.w. along with AFB1. The pathologic changes, serobiochemical parameters, oxidative stress, histological changes, and the molecular disruption, induced by AFB1 in both liver and kidney were obviously and significantly ameliorated after BTE and/or CMN treatments in variable potencies where both agents showed the most effective antitoxic capacities.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Curcumina , Aflatoxina B1/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Curcumina/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Chá
16.
Chem Biol Drug Des ; 96(4): 1148-1161, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32400098

RESUMO

In this work, we have successfully upgraded the crab wastes into Pd(II) complex of Gboxin analog-chitooligosaccharides conjugate (Pd(II)COS@GbA). This new complex has a high capacity to inhibit the proliferation of prostate cancer cells (IC50  = 1.92 µg/ml). This activity could be attributed to its ability to induce mitochondrial fragmentation through increasing mitochondrial fission dynamin-related protein 1 (p < .05) and down-regulation of optic atrophy 1 proteins (p < .05). Moreover, this complex can effectively disrupt ATP synthase action leading to declined ATP production, along with downstream of ATPase inhibitor factor1 that hinder energy production in the cancer cells. Also, it has an anti-inflammatory effect by triggering modulators for the release of inflammatory molecules such as TNF-α (p < .05), IL-6 (p < .05), and mRNA transcripts of COX-II (p < .01). Therefore, Pd(II)COS@GbA exhibited significant anti-prostate cancer activity through different mechanisms in inducing energy depletion and mitochondrial fragmentation leading to disrupted oxidative phosphorylation (OXPHOS). Complex Pd(II)COS@GbA is more cytotoxic for PC3 than RWPE-1 which in turn means it is may act as a selective cytotoxic agent for prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Quitina/análogos & derivados , Metabolismo Energético/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Paládio/química , Linhagem Celular Tumoral , Quitina/química , Quitosana , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Oligossacarídeos , Fosforilação Oxidativa
17.
Saudi Med J ; 41(3): 296-303, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32114603

RESUMO

OBJECTIVES: To assess the knowledge, attitudes, and practices of adults regarding the implementation of calorie labeling in restaurants in Riyadh, Saudi Arabia. METHODS: This was a cross-sectional study of 1443 adults invited to complete a self-administered questionnaire consisting of 4 parts that assess demographics, knowledge, attitudes, and practices of mandatory menu labeling. The survey was conducted in all 5 regions of Riyadh. RESULTS: We entered 1265 surveys into final data analysis with a response rate of 88%. Of this, 1036 participants (82%) understood the meaning and values of calories, while 53% knew the average daily caloric intake. Regarding participants' attitudes, 1053 (83%) perceived the importance of calorie labeling and (88%) supported this policy. Approximately 50% (n=626) of the participants were significantly more likely to be influenced by the calorie labeling to place a healthier order. Married (p=0.050), educated (p less than 0.001), and higher monthly income (p less than 0.001) were significantly influenced to place a healthier restaurant order compared to their peers. CONCLUSION: Adults in Riyadh showed satisfactory knowledge, attitude, and practice since the implementation of this policy. Our findings showed that knowing the value of calories and average caloric intake had a significant positive influence for a healthier diet. This highlights the importance of menu labeling regulations campaigns for the public.


Assuntos
Dieta Saudável , Ingestão de Energia , Rotulagem de Alimentos , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Política Nutricional , Saúde Pública , Restaurantes , Adolescente , Adulto , Estudos Transversais , Escolaridade , Feminino , Promoção da Saúde , Humanos , Renda , Masculino , Estado Civil , Pessoa de Meia-Idade , Arábia Saudita , Inquéritos e Questionários , Adulto Jovem
18.
Folia Histochem Cytobiol ; 57(4): 159-167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31746453

RESUMO

INTRODUCTION: The extremely-low frequency electromagnetic field (ELFEMF) has been proposed for use in cancer therapy since it was found that magnetic waves interfere with many biological processes. Gold nanoparticles (Au-NPs) have been widely used for drug delivery during cancer in vitro studies due to their low cytotoxity and high biocompatibility. The electroporation of cancer cells in a presence of Au-NPs (EP Au-NPs) can induce cell apoptosis, alterations of cell cycle profile and morphological changes. The impact of ELFEMF and EP Au-NPs on morphology, cell cycle and activation of apoptosis-associated genes on Hep-2 laryngeal cancer cell line has not been studied yet. MATERIALS AND METHODS: ELFEMF on Hep-2 cells were carried out using four different conditions: 25/50 mT at 15/30 min, while Au-NPs were used as direct contact (DC) or with electroporation (EP, 10 pulses at 200V, equal time intervals of 4 sec). MTT assay was used to check the toxicity of DC Au-NPs. Expression of CASP3, P53, BAX and BCL2 genes was quantified using qPCR. Cell cycle was analyzed by flow cytometry. Hematoxylin and eosin (HE) staining was used to observe cell morphology. RESULTS: Calculated IC50 of DC Au-NPs 24.36 µM (4.79 µg/ml) and such concentration was used for further DC and EP AuNPs experiments. The up-regulation of pro-apoptotic genes (CASP3, P53, BAX) and decreased expression of BCL2, respectively, was observed for all analyzed conditions with the highest differences for EP AuNPs and ELFEMF 50 mT/30 min in comparison to control cells. The highest content of cells arrested in G2/M phase was observed in ELFEMF-treated cells for 30 min both at 25 or 50 mT, while the cells treated with EP AuNPs or ELFEMF 50 mT/15 min showed highest ratios of apoptotic cells. HE staining of electroporated cells and cells exposed to ELFEMF's low and higher frequencies for different times showed nuclear pleomorphic cells. Numerous apoptotic bodies were observed in the irregular cell membrane of neoplastic and necrotic cells with mixed euchromatin and heterochromatin. CONCLUSIONS: Our observations indicate that treatment of Hep-2 laryngeal cancer cells with ELFEMF for 30 min at 25-50 mT and EP Au-NPs can cause cell damage inducing apoptosis and cell cycle arrest.


Assuntos
Antineoplásicos/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Campos Eletromagnéticos , Eletroporação/métodos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/toxicidade , Regulação para Cima
19.
Saudi Med J ; 40(11): 1105-1110, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31707406

RESUMO

OBJECTIVES: To identify risk factors associated with carbapenem-resistant Enterobacteriaceae (CRE) infections among hospitalized children at King Fahad Medical City, Riyadh, Saudi Arabia. METHODS: A retrospective matched case-control study was conducted in pediatric patients with CRE infection at King Fahad Medical City, Riyadh, Saudi Arabia between January 2016-2017. RESULTS: During the study period, 19 CRE cases and 37 controls were identified for analysis. Children  ≤17 years (mean age±SD for cases was 43.9±46 months and controls was 29.2±52.2 months) were included in the study. Several factors associated with CRE infections were identified, which included, central venous catheter (CVC) line placement (p=0.023; confidence interval [CI]: 0.97-85.77), recent surgical procedures (p=0.006; CI: 1.30-9.28), invasive procedures (p greater than 0.001; CI: 1.98-21.18), use of prior antibiotics (p=0.008; CI: 1.38-24.62), and carbapenem exposure in the past 3 months (p=0.004; CI: 1.09-12.20). Among the cases, Klebsiella pneumonia was the most commonly identified (47%) followed by Escherichia coli (31%). Carbapenem-resistant Enterobacteriaceae was associated with increased comorbidities and prolonged hospitalization however, no mortalities were reported. CONCLUSION: This study identified prior antibiotic exposure, recent surgery and the use of invasive procedures as significant risk factors for colonization or infection with CRE. Also, the need for public awareness, continuing education for healthcare professionals, optimum use of invasive devices, enhanced surveillance, and antimicrobial stewardship are highlighted here which can limit CRE transmission in healthcare facilities.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Criança Hospitalizada , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Arábia Saudita
20.
Dent Mater J ; 34(2): 148-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25736257

RESUMO

The present in vitro study sought to determine the effects of myrrh-containing solutions on common suture materials used in periodontal surgery. Three commonly used suture materials (silk, polyglactin 910, polytetrafluoroethylene) were immersed in four thermostatically controlled experimental media to simulate daily oral rinsing activity, namely -artificial saliva, normal saline solution with 0.2% Commiphora myrrh, full-concentration (100%) Commiphora myrrh oil, and a myrrh-containing commercial mouthwash. Tensile strength was measured at the end of each day using an Instron tensile testing machine. Silk sutures were susceptible to tensile strength loss when exposed to 0.2% myrrh solution once daily for 5 days. Myrrh-containing commercial mouthwash had no effect on tensile strength, but all three suture materials lost tensile strength when exposed to 100% myrrh oil. For patients that routinely use myrrh mouthwashes postoperatively, findings of this study suggested that silk sutures might not be the optimal material choice.


Assuntos
Resistência à Tração/efeitos dos fármacos , Terpenos/farmacologia , Materiais Dentários , Técnicas In Vitro , Teste de Materiais , Poliglactina 910 , Politetrafluoretileno , Seda , Suturas
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