Common Genetic Variants in SIRT1 Gene Promoter and Type 2 Diabetes Mellitus in Saudi Arabia.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is common in Saudi Arabia and represents a major health concern. Silent information regulator of transcription-1 (SIRT1) positively influences insulin sensitivity and might contribute to the pathogenesis of T2DM. This study aimed to investigate the frequency of two common functional single nucleotide polymorphisms (SNPs) in the promoter region of SIRT1; rs12778366 (T>C) and rs3758391 (T>C) in Saudi Arabian population and examine any association with T2DM. METHODS: A total of 445 volunteers were divided into 224 healthy controls and 221 patients previously diagnosed with T2DM. Genomic DNA was extracted from all samples and genotyped for SIRT1 rs12778366 and rs3758391 SNPs by TaqMan RT-PCR allelic discrimination assay. Logistic regression analysis was used to establish any relationship between these polymorphisms and T2DM. RESULTS: In the total study population, rs12778366 genotype frequencies were TT (89.2%), TC (10.3%), and CC (0.45%) and for the rs3758391 they were TT (16.4%), TC (44.5%), and CC (39.1%). The distribution of these genotypes, in both polymorphisms, were similar among T2DM and controls. Logistic regression analysis confirmed the lack of association between the presence of CC or CT variants and T2DM for rs12778366 and rs3758391 SNP (OR = 0.98 [CI]: 0.55 - 1.75; p = 0.999 and OR= 0.75; [CI]: 0.45 - 1.24; p = 0.313), respectively. CONCLUSIONS: This study revealed the frequency of SIRT1 rs12778366 and rs3758391 SNPs in our population and reported no association between these polymorphisms and the risk for T2DM. This finding might add to the growing body of literature exploring the genetics of T2DM.

Evaluation of Renal Function in COVID-19 Patients by Using Urinalysis Following the Administration of Vancomycin.

BACKGROUND: The aim of this study was to evaluate renal function by urinalysis in COVID-19 patients following the administration of vancomycin. METHODS: A retrospective observational study was performed between October 2020 and January 2021, during which time patients were hospitalized in the Prince Mohammed Bin Abdulaziz Hospital in Riyadh, Saudi Arabia. The patients were free of kidney disease. Urinalysis was performed by an automated laboratory system, and the collected results were based upon age, gender, diabetic status, whether the patients had received vancomycin, the mortality rate, and the urinalysis panel including coinfection by bacteria and yeast. RESULTS: A total of 227 patients were included in this study, 147 (64.75%) of whom were male and 80 (35.25%) of whom were female; 54.63% were diabetic, 11.89% were prediabetic, and 33.48% were non-diabetic patients. Proteinuria, hematuria, glycosuria, coinfection, and ketonuria were detected among all participants within the study group, specifically among diabetic patients. The mortality rate was 16.2% among the study group; 6.6% had re-ceived vancomycin, and 9.6% had not received vancomycin. No significant correlation was found between nephrotoxicity and abnormalities in the urine and the mortality rate among members of our study group. CONCLUSIONS: Proteinuria, hematuria, glycosuria, ketonuria, and coinfection were common among members of our study group, especially in the diabetic group. Urinalysis abnormalities were less frequent in the vancomycin group than in the others, except the prediabetic group. No correlation between mortality and vancomycin was identified.

Seroprevalence of IgM and IgG Against SARS-CoV-2 after Two Doses of Pfizer-BioNTech COVID-19 Vaccine in Women with Breast Cancer.

BACKGROUND: This study evaluates the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 after two doses of Pfizer-BioNTech COVID-19 vaccination from women with breast cancer in Jazan city Kingdom of Saudi Arabia, antibody detections were performed one month and three months after the administration of the second dose. METHODS: Overall, 103 breast cancer patients were included. Individuals who had had two doses of Pfizer-BioNTech vaccine, patients who were earlier diagnosed with COVID-19 infection, had not finalized immunization plan, or who received the second dose recently were excluded from the study. The antibodies detection test was run according to the manufacturer's directions of Viva Diag™ SARS-CoV-2 IgM/IgG Rapid Test (COVID-19 IgM/IgG Rapid Test). RESULTS: This study included 62 (60.2%) and 41 (39.8%) patients with invasive ductal carcinoma and invasive lobular carcinoma, respectively. The age, median and interquartile range (IQR) was 54.0 (26) years. Regarding reactivity of antibodies, after one month IgM antibody showed 64 (62.1%) positive and 39 (37.9%) negative while IgG antibody showed positive results in all patients. After three months IgM antibody showed 44 (42.7%) positive and 59 (57.3%) negative, while IgG showed 87 (84.5%) positive and 16 (15.5%) negative. There were significant differences in the IgM and IgG seropositivity. There were 19.3% patients with ductal carcinoma who were positive and then turned negative versus 17.7% who were positive and then turned negative, respectively (p < 0.001). There were significant differences in IgM antibody positivity among different age groups. CONCLUSIONS: Our results recommend the importance of screening for an antibody response for breast cancer patient after immunization in order to reveal persons who need early and late extra enhancing vaccine dose. Upcoming studies recommended to estimate different methods that raise cancer patients' immune response.

In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from Delphinium chitralense.

This study reports the isolation of three new C20 diterpenoid alkaloids, Chitralinine A-C (1-3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1-3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC50 value of 11.64 ± 0.08 µM against AChE, and 24.31 ± 0.33 µM against BChE, respectively. The molecular docking reflected a binding free energy of -16.400 K Cal-mol-1 for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer's disease.

Attenuation of Scopolamine-Induced Amnesia via Cholinergic Modulation in Mice by Synthetic Curcumin Analogs.

Alzheimer's disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a−1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested.

Evaluation of in-vitro and in-vivo antimicrobial potential of Typha elephantina leaves extracts using Cyprinus carpio as a research model.

Present study investigate the in-vitro antibacterial and antifungal potential of Typha elephantina leaves aqueous extract (T. Eaq), ethanolic extract (T. Eeth) and methanolic extract (T. Emth) at different dosages against selected bacteria and fungi using dis diffusion method and Potato Dextrose Agar method. The study was also proceeded in- vivo against one strain of fungi (Aspergillus niger) using aqueous (T. Eaq) extract only. In-vitro study showed that Citrobacter freundii was highly sensitive while Salmonella typhimurium was the least among all. The antifungal activity was dose dependent and differs according to the fungal strain. Aspergillus niger was highly sensitive in order of aqueous extract (T. Eaq), ethanolic extract (T. Eeth) and methanolic extract (T.Emth), followed by Alterneria solani, Candida albicans and Aspergillus ustus. The in-vivo antifungal study was carried using Cyprinus carpio which were first infected with Aspergillus niger and then treated with (T. Eaq) at different doses. During in-vivo study various hematobiochemicl parameters and bio-accumulative stress of some heavy metals were assessed. Highly significant (P<0.05) remedial effects were observed at day 21st of treatment with extract at 100mg/ kg body weight. Differential accumulation was found i.e in skin the accumulation was highest followed by intestine gills and muscles tissues. Liver showed least accumulation.

Study of Structurally Diverse Currently Used and Recently Developed Antimycobacterial Drugs.

Despite major antimicrobial therapeutic advancements, widespread use and misuse of antimicrobial drugs have increased antimicrobial drug resistance, posing a severe danger to public health. In particular, the emergence of multidrug-resistant bacteria has provided considerable difficulty in the treatment of pathogenic infections. As a result, the creation of novel drugs to treat resistant bacteria is one of the most significant disciplines of antimicrobial research today. TB therapy has recently gained a lot of attention, in addition to developing novel and efficient antibacterial drugs to battle multidrug-resistant illnesses. The use of a different class of drugs, such as well-known drugs, their derivatives, and various new heterocyclic compounds like nitroimidazoles, imidazole analogues, triazoles, imidazopyridines, quinolines, purines, as well as thioactomycin, mefloquine, deazapteridines, benzothiadiazine and other molecules such as benzoxazines, diterpenoids, tryptanthin and phenazine and toluidine analogues followed by many other classes of compounds and their effects are also discussed. As a result, current and newly found antitubercular drugs and their toxicities and mode of action have been focused.

Prognostic Value of Evaluating Platelet Role, Count and Indices in Laboratory Diagnosis of Different Types of Solid Malignancies.

Platelets are associated with the processes that aid in tumour growth and progression. Platelet Count (PLT) and platelet indices like Mean Platelet Volume (MPV), Platelet Large Cell Ratio (P-LCR), Plateletcrit (PCT) and Platelet Distribution Width (PDW) are markers that are linked with platelet activities in cancer. This review involves the evaluation of PLT, MPV and PCT in different cancers. Platelets actions should be always monitored during several diseases, as their potential exceeds the classical function in preventing bleeding. Vast roles of platelets were discovered in several biological functions. Therefore, studying their indices can be effective in the diagnosis of several disorders including cancer.

Core Proteomics and Immunoinformatic Approaches to Design a Multiepitope Reverse Vaccine Candidate against Chagas Disease.

Chagas disease is a tropical ailment indigenous to South America and caused by the protozoan parasite Trypanosoma cruzi, which has serious health consequences globally. Insect vectors transmit the parasite and, due to the lack of vaccine availability and limited treatment options, we implemented an integrated core proteomics analysis to design a reverse vaccine candidate based on immune epitopes for disease control. Firstly, T. cruzi core proteomics was used to identify immunodominant epitopes. Therefore, we designed the vaccine sequence to be non-allergic, antigenic, immunogenic, and to have better solubility. After predicting the tertiary structure, docking and molecular dynamics simulation (MDS) were performed with TLR4, MHC-I, and MHC-II receptors to discover the binding affinities. The final vaccine design demonstrated significant hydrogen bond interactions upon docking with TLR4, MHC-I, and MHC-II receptors. This indicated the efficacy of the vaccine candidate. A server-based immune simulation approach was generated to predict the efficacy. Significant structural compactness and binding stability were found based on MDS. Finally, by optimizing codons on Escherichia coli K12, a high GC content and CAI value were obtained, which were then incorporated into the cloning vector pET2+ (a). Thus, the developed vaccine sequence may be a viable therapy option for Chagas disease.

Investigation of Antistress and Antidepressant Activities of Synthetic Curcumin Analogues: Behavioral and Biomarker Approach.

Depression is a serious psychiatric disorder that affects millions of individuals all over the world, thus demanding special attention from researchers in order to investigate its effective remedies. Curcumin, along with its synthetic derivatives, is recognized for its incredible pharmacological activities. In this study, methyl, methoxy and chloro-substituent synthetic curcumin analogues C1-C3 were respectively tested for free radical-scavenging activity. Behavioral studies were performed using chemical-induced and swimming endurance tests as stress models, and forced swim tests (FSTs) and tail suspension tests (TSTs) as depression mice models. Biochemical examinations were performed after a scopolamine-induced stress model by decapitating the mice, and brain tissues were isolated for biochemical assessment of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). The curcumin analogue C2 exhibited higher DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azinobis-3-ethylbenzothiazo-line-6-sulphonate) free radical-scavenging potential, having IC50 values of 45.18 µg/mL and 62.31 µg/mL, respectively, in comparison with reference curcumin and tocopherol. In the chemical-induced test, C2 (80.17%), C3 (72.79%) and C1 (51.85%) revealed higher antistress responses by significantly reducing the number of writhes, whereas the immobility time was significantly reduced by C2 and C3 in the swimming endurance test, indicating excellent antistress potential. Similarly, C2 and C3 significantly reduced the immobility times in FST and TST, demonstrating their antidepressant properties. The biomarkers study revealed that these compounds significantly enhanced hippocampus CAT, SOD and GSH, and reduced MDA levels in the scopolamine-induced stress mice model. These findings suggest the potential of curcumin analogues (C2 and C3) as antistress and antidepressant agents.

Rasch and Confirmatory Factor Analyses of the Arabic Version of the Diabetes Self-Management Scale (DSMS): An Intercultural Approach.

The current study was designed to validate the Arabic version of the Diabetes Self-Management Scale (DSMS) using Rasch and confirmatory factor analyses. This included person and item fit, separation, and reliability; rating scale functionality to evidence substantive validity; unidimensional structure to evidence structural validity; and item technical quality to evidence content validity. The study was conducted between September 2021 and March 2022. Utilizing AMOS-based confirmatory factor analysis (CFA), the study also assured the dimensionality of the DSMS. The participants were 103 diabetic patients in Saudi Arabia with a mean age of 44.72 years (standard deviation = 17.35). The analysis was performed using a trichotomous rating scale, and only one item exhibited a misfit (DSMS14). The item difficulty range was -1.0 to +1.0 logits, while the person's ability range was -3.0 to +3.0 logits. The first construct proved one Rasch dimension, which was explained and further analyzed using AMOS-CFA for the one-factor model. The DSMS was shown to be beneficial as a screening instrument for patient-reported diabetes self-management, despite several flaws that need to be addressed to improve the scale further.

Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models.

Alzheimer's disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a wide spectrum of biological properties. In this regard, the antioxidant potentials of mono-carbonyl curcumin analogues (h1−h5) were investigated using in vitro antioxidant assays and hippocampal-based in vivo mouse models such as light−dark box, hole board, and Y-maze tests. In the in vitro assay, mono-carbonyl curcumin analogues h2 and h3 with methoxy and chloro-substituents, respectively, showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethylbenzothiazo-line-6-sulfonate (ABTS) free radical scavenging activities. In the in vivo studies, scopolamine administration significantly (p < 0.001) induced oxidative stress and memory impairment in mice, in comparison to the normal control group. The pretreatment with mono-carbonyl curcumin analogues, specifically h2 and h3, significantly decreased (123.71 ± 15.23 s (p < 0.001), n = 8; 156.53 ± 14.13 s (p < 0.001), n = 8) the duration of time spent in the light chamber and significantly enhanced (253.95 ± 19.05 s (p < 0.001), n = 8, and 239.57 ± 9.98 s (p < 0.001), n = 8) the time spent in the dark compartment in the light−dark box arena. The numbers of hole pokings were significantly (p < 0.001, n = 8) enhanced in the hole board test and substantially increased the percent spontaneous alternation performance (SAP %) in the Y-maze mouse models in comparison to the stress control group. In the biomarker analysis, the significant reduction in the lipid peroxidation (MDA) level and enhanced catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) activities in the brain hippocampus reveal their antioxidant and memory enhancing potentials. However, further research is needed to find out the appropriate mechanism of reducing oxidative stress in pathological models.

Evaluation of CD4+:CD8+ Ratio in Patients With Cervical Cancer and the Levels of Inflammatory Markers.

BACKGROUND/AIM: Cervical cancer remains a major public health concern. The ratio of CD4+:CD8+ T-cells is used to evaluate the immune system function. This study aimed to explore the CD4+:CD8+ T-cell ratio in relation to the glycemic status, inflammatory markers, vitamin D, and vitamin B12 in patients with early diagnosed cervical cancer. PATIENTS AND METHODS: This is a cross-sectional study. Blood samples were collected for flow cytometry analysis. Information regarding Papanicolaou (Pap) smears and colposcopy investigations were collected from 152 women with type 2 diabetes admitted to East Jeddah Hospital, Jeddah, Saudi Arabia, between January 2018 and January 2021. RESULTS: Patients with early cervical carcinoma and a higher CD4+:CD8+ ratio (>1.2) had a higher C-reactive protein (CRP) level than those with a lower CD4+:CD8+ ratio (Mean±SD=13.75±13.3 vs. 10.85±8.1; p-value=0.034). Patients with early cervical carcinoma, diabetes, and higher CD4+:CD8+ ratio (>1.2) had a higher blood HbA1c percent than those with a lower CD4+:CD8+ ratio. CONCLUSION: A high CD4+:CD8+ T-cells ratio was associated with an increased HbA1c% and CRP levels in women with diabetes diagnosed with early cervical carcinoma, which can induce inflammation in early diagnosed patients with cervical cancer.

Recent Insights and Multifactorial Applications of Carbon Nanotubes.

Nanotechnology has undergone significant development in recent years, particularly in the fabrication of sensors with a wide range of applications. The backbone of nanotechnology is nanostructures, which are determined on a nanoscale. Nanoparticles are abundant throughout the universe and are thought to be essential building components in the process of planet creation. Nanotechnology is generally concerned with structures that are between 1 and 100 nm in at least one dimension and involves the production of materials or electronics that are that small. Carbon nanotubes (CNTs) are carbon-based nanomaterials that have the structure of tubes. Carbon nanotubes are often referred to as the kings of nanomaterials. The diameter of carbon is determined in nanometers. They are formed from graphite sheets and are available in a variety of colors. Carbon nanotubes have a number of characteristics, including high flexibility, good thermal conductivity, low density, and chemical stability. Carbon nanotubes have played an important part in nanotechnology, semiconductors, optical and other branches of materials engineering owing to their remarkable features. Several of the applications addressed in this review have already been developed and used to benefit people worldwide. CNTs have been discussed in several domains, including industry, construction, adsorption, sensors, silicon chips, water purifiers, and biomedical uses, to show many treatments such as injecting CNTs into kidney cancers in rats, drug delivery, and directing a near-infrared laser at the cancers. With the orderly development of research in this field, additional therapeutic modalities will be identified, mainly for dispersion and densification techniques and targeted drug delivery systems for managing and curing posterior cortical atrophy. This review discusses the characteristics of carbon nanotubes as well as therapeutic applications such as medical diagnostics and drug delivery.

Clinical Findings of COVID-19 Patients at High and Average Altitudes in Saudi Arabia.

<b>Background and Objective:</b> Coronavirus disease 2019 (COVID-19), also known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), became a global health issue that influenced the lives of billions of people all over the world. The goal of this study was to investigate the clinical findings and routine laboratory evaluations of COVID-19 patients in both average- and high-altitude settings in Saudi Arabia. <b>Materials and Methods:</b> A comparative study to explore the clinical characteristics and Laboratory tests results of COVID-19 patients at both high and average altitudes in Saudi Arabia has been conducted. The study included a total number of 103 patients (53 patients comprising the high-altitude group living in Taif, Saudi Arabia and 50 patients comprising the average-altitude group living in Al Ahsa, Saudi Arabia) were included in the study. Patients were diagnosed with SARS-CoV-2-positive by PCR test. Clinical characteristics, laboratory test results and symptoms of adult patients were collected and expressed as mean and standard deviation. Statistical analysis was done using SPSS software to compare between both groups and significance was considered when the p-value is less than 0.05. <b>Results:</b> Approximately 55.3% of the total cases were male with a mean age of 40.16±12.47 years. There were highly statistically significant differences between the groups in age, heart rate (p<0.001). There were also statistically significant differences between the groups in temperature, SpO₂, fever, myalgia, shortness of breath and loss of smell and taste. <b>Conclusion:</b> The current study provides an understanding of the clinical and laboratory investigations of COVID-19 patients in two regions (high altitude and average altitude) in Saudi Arabia.

Seroprevalence of Toxoplasma gondii, Rubella, Group A Streptococcus, CMV and HSV-1 in COVID-19 Patients with Vitamin D Deficiency.

<b>Background and Objective:</b> In recent years, respiratory tract viral infections have caused many pandemics that impact the whole world. To investigate the seropositivity of <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> in recovered COVID-19 patients and correlate these findings with vitamin D levels. <b>Materials and Methods:</b> A total of 417 COVID-19 patients with diarrhoea were enrolled in this study. Vitamin D and seroprevalence for <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> were evaluated and correlated. <b>Results:</b> It was found that recent infection in COVID-19 patients with HSV-1, rubella, <i>Toxoplasma</i> and CMV, respectively. IgG was detected indicating the development of adaptive immunity with all microbes. <b>Conclusion:</b> Current study detected a correlation between vitamin D levels and HSV-1 and no correlation between this infection and vitamin D deficiency with the other microbes.

Identification of novel CD8+ T cell epitopes in human herpesvirus 6B U11 and U90.

Human herpesvirus 6B (HHV6B) infects over 90% of the population, and normally establishes a latent infection, where episodes of reactivation are asymptomatic. However, in immunocompromised patients HHV6B reactivation is associated with high morbidity and mortality. Cellular immunotherapy has been utilised against other herpesvirus in immunocompromised settings. However, limited information on the immune response against HHV6B has hampered the development of immunotherapy for HHV6B-driven disease. In this study, we have analysed the cellular immune response against four HHV6B antigens in a panel of 30 healthy donors. We show that the base-line level of T cell reactivity in peripheral blood is very low to undetectable. A short-term reactivation step enabled expansion of T cell responses, and all donors responded to at least 1 antigen, but more commonly 3 or 4. A hierarchy of immunogenicity was determined with antigens U90 and U54 being co-dominant, followed by U11 and U39. Putative CD8+ T cell epitopes were mapped to U90 and U11, predicted to be presented in the context of HLA-A1, A29, B39 and C6. T cells reactive against these novel epitopes were able to recognise virus-infected cells. Our data is supportive of the application and on-going development of T cell immunotherapy against HHVB-driven disease in the immunocompromised host.