Search Results (34)

The present study explored anti-tubercular pyrrole derivatives against cancer targets using different in silico and in vitro approaches. Initially, nineteen anti-tubercular pyrrolyl benzohydrazide derivatives were screened against a potent cancer target PLK1 using an AutoDock Vina approach. Out of the nineteen derivatives, the two most potent derivatives C8 [N′-(4-(1H-pyrrol-1-yl) benzoyl)-3-chlorobenzohydrazide] and C18 [N′-(4-(1H-pyrrol-1-yl) benzoyl)-4-nitrobenzohydrazide], were subjected to molecular simulation analysis for a 100 ns trajectory. Further, these two derivatives were tested against A549, MCF-7, and HepG2 cell lines using an MTT proliferation assay. Apoptotic cell cycle and DAPI assays were also performed for C8 on A549 cell lines. Molecular dynamic analysis revealed that the stability of the C8–PLK1 protein complex during the 100 ns trajectory run was better than that of the C18–PLK1 protein complex. In addition, C8 showed lower IC₅₀ values against the tested cell lines, in comparison to C18. Thus, C8 was selected for cell cycle, apoptosis, and DAPI analysis. Interestingly, C8 resulted in the significant cell cycle arrest of A549 cells at the G2/M phase, and annexin V-FITC/PI showed a significant increase (from 6.27% to 60.52%) in the percentage of apoptotic A549 cells. The present findings suggest that the anti-tubercular compound (C8) could be translated into a potent repurposed candidate against lung cancer. Nevertheless, in vivo assessment is necessary to further confirm the outcome and its clinical translation. Full article

Osteoporosis is a major public health concern in Saudi Arabia’s aging population. There is particularly limited information on how diet affects bone loss in this ethnic group. The purpose of this study was to examine the association between dietary calcium (Ca) intake and osteoporosis risk in Saudi adults. A total of 1950 patients (416 males and 1534 females) with known risk factors for osteoporosis participated in this cross-sectional study. A short questionnaire (CaQ) was used to assess dietary Ca intakes in patients attending tertiary hospitals in Riyadh City. The prevalence of osteoporosis was 21.3% and was more common in females (93.5%). Patients with osteoporosis were older (p < 0.001) and had lower BMI (p < 0.001). Results showed that the overall mean Ca intake was only 445.1 mg/day (recommended dietary intake of 1300 mg/day). Tea intake (OR = 0.8 95%CI: 0.7–1.0; p = 0.02) and consumption of fish and eggs (OR = 0.9 95%CI: 0.8–1.0; p = 0.01) were significantly associated with a lower risk of osteoporosis. Furthermore, consumption of biscuits, cake and bread slices were significantly associated with higher incidence of osteoporosis (OR = 1.3 95%CI: 1.0–1.5; p = 0.02). In conclusion, extremely low dietary Ca intake was observed among Saudi adults already at risk of osteoporosis. A balanced diet including high amount of Ca, vitamin D and omega-3 fatty acids accompanied by limiting consumption of foods high in saturated fats and glycemic index may be helpful in reducing osteoporosis risk in the Saudi adult population. Full article

The realm of the Internet of Things (IoT), while continually transforming as a novel paradigm in the nexus of technology and education, still contends with numerous obstacles that hinder its incorporation into higher education institutions’ (HEIs) e-learning platforms. Despite substantial strides in IoT utilization from industrialized nations—the United States, the United Kingdom, Japan, and China serving as prime exemplars—the scope of its implementation in developing countries, notably Saudi Arabia, Malaysia, Pakistan, and Bangladesh, lags behind. A significant gap exists in research centered on the trajectory of IoT integration within e-learning systems of economically disadvantaged nations. Specifically, this study centers on Saudi Arabia to illuminate the main factors catalyzing or encumbering IoT uptake within its HEIs’ e-learning sector. As a preliminary step, this research has embarked on an exhaustive dissection of prior studies to unearth critical variables implicated in the IoT adoption process. Subsequently, we employed an inferential methodology, amassing data from 384 respondents in Saudi Arabian HEIs. Our examination divulges that usability, accessibility, technical support, and individual proficiencies considerably contribute to the rate of IoT incorporation. Furthermore, our data infer that financial obstacles, self-efficacy, interactive capability, online surveillance, automated attendance tracking, training programs, network and data safeguarding measures, and relevant tools significantly influence IoT adoption. Contrarily, factors such as accessibility, internet quality, infrastructure preparedness, usability, privacy concerns, and faculty support appeared to have a negligible impact on the adoption rates within HEIs. This research culminates in offering concrete recommendations to bolster IoT integration within Saudi Arabian HEIs, presenting valuable insights for government entities, policy architects, and HEIs to address the hurdles associated with IoT implementation in the higher education sector. Full article

Breast cancer is the most prevalent type of malignancy among females as per the report of the World Health Organization. There are several established chemotherapeutic regimes for the clinical management of different solid cancers; however, the after-effects of these therapeutics serve as a significant limiting factor. The natural triterpenoid compound, gedunin is one of the principal phytoconstituent found in Azadirachta indica. In this study, we have investigated the anticancer potential of gedunin against human breast cancer MDA-MB-231 and MCF-7 cells. Based on computational studies, gedunin exhibited significantly higher binding affinity of −7.1 and −6.2 Kcal/mol towards Janus kinase (JAK) and STAT proteins, respectively. Further, the anticancer potential of gedunin against human breast cancer was studied using hormone-independent and -dependent MCF-7 and MDA-MB-231 cell lines, respectively. The results indicated that gedunin inhibited the growth and multiplication of both MCF-7 and MDA-MB-231 cells. The nuclear fragmentation and ROS were qualitatively enhanced in the treated MCF-7 and MDA-MB-231 cells in comparison to untreated cells. The caspase-3 level was significantly enhanced with a concomitant decline in JAK1 and STAT3 mRNA expression. Based on these results, gedunin might be considered as a potential therapeutic lead against hormone-dependent and -independent breast cancer MCF-7 and MDA-MB-231 cells, respectively. However, further detailed mechanistic studies are warranted to conclusively establish the anti-breast cancer effects. Full article

Prediabetes is a reversible, intermediate stage of type 2 diabetes mellitus (T2DM). Lifestyle changes that include healthy diet and exercise can substantially reduce progression to T2DM. The present study explored the association of 37 T2DM- and obesity-linked single nucleotide polymorphisms (SNPs) with prediabetes risk in a homogenous Saudi Arabian population. A total of 1129 Saudi adults [332 with prediabetes (29%) and 797 normoglycemic controls] were randomly selected and genotyped using the KASPar SNP genotyping method. Anthropometric and various serological parameters were measured following standard procedures. Heterozygous GA of HNF4A-rs4812829 (0.64; 95% CI 0.47–0.86; p < 0.01), heterozygous TC of WFS1-rs1801214 (0.60; 95% confidence interval (CI) 0.44–0.80; p < 0.01), heterozygous GA of DUSP9-rs5945326 (0.60; 95% CI 0.39–0.92; p = 0.01), heterozygous GA of ZFAND6-rs11634397 (0.75; 95% CI 0.56–1.01; p = 0.05), and homozygous AA of FTO-rs11642841 (1.50; 95% CI 0.8–1.45; p = 0.03) were significantly associated with prediabetes, independent of age and body mass index (BMI). Additionally, C-reactive protein (CRP) levels in rs11634397 (AA) with a median of 5389.0 (2767.4–7412.8) were significantly higher than in the heterozygous GA genotype with a median of 1736.3 (1024.4–4452.0) (p < 0.01). In conclusion, only five of the 37 genetic variants previously linked to T2DM and obesity in the Saudi Arabian population [HNF4A-rs4812829, WFS1-rs1801214, DUSP9-rs5945326, ZFAND6-rs11634397, FTO-rs11642841] were associated with prediabetes susceptibility. Prospective studies are needed to confirm the potential clinical value of the studied genetic variants of interest. Full article

Among the various types of cancer, lung cancer accounts for the highest number of fatalities across the globe. A combination of different cancer chemotherapeutics is regarded as an effective strategy for clinical management of different cancers. Ganetespib (GAN) is a well-established hsp90 inhibitor with enhanced pharmacological properties in comparison with its first-generation counterparts. Previous preclinical studies have shown that GAN exerts significant effects against cancer cells; however, its therapeutic effects against non-small cell lung cancer (NSCLC) A549 cells, achieved by modulating the expression of the NF-κB/p65 signaling pathway, remains unexplored. In this study, the combinatorial effect of GAN and methotrexate (MTX) against lung carcinomas was investigated through both in silico and in vitro studies. A combinatorial treatment regimen of GAN/MTX exerted more significant cytotoxic effects (p < 0.001) against A549 cells than individual treatments. The GAN/MTX combination also instigated nuclear fragmentation followed by augmentation in intracellular ROS levels (p < 0.001). The elevated ROS in A549 cells upon exposure to GAN/MTX combinatorial regimen was concomitantly accompanied with a remarkable reduction in mitochondrial viability. In addition, it was observed that the GAN/MTX combination succeeded in elevating caspase-3 activity and downregulating the expression levels of anti-apoptotic mediators Bcl2 and survivin in NSCLC A549 cells. Most importantly, the GAN/MTX combinatorial regimen impeded the activation of the NF-kB/p65 signaling pathway via repression of the expression of E-cadherin and N-cadherin, which was confirmed by molecular docking studies. Collectively, these findings demonstrated the synergistic effect of the GAN/MTX combinatorial regimen in suppressing the growth of A549 cells by modulating the NF-κB/p65 signaling pathway. Full article

The advent of new antibiotics has helped clinicians to control severe bacterial infections. Despite this, inappropriate and redundant use of antibiotics, inadequate diagnosis, and smart resistant mechanisms developed by pathogens sometimes lead to the failure of treatment strategies. The genotypic analysis of clinical samples revealed that the rapid spread of extended-spectrum β-lactamases (ESBLs) genes is one of the most common approaches acquired by bacterial pathogens to become resistant. The scenario compelled the researchers to prioritize the design and development of novel and effective therapeutic options. Nanotechnology has emerged as a plausible groundbreaking tool against resistant infectious pathogens. Numerous reports suggested that inorganic nanomaterials, specifically gold nanoparticles (AuNPs), have converted unresponsive antibiotics into potent ones against multi-drug resistant pathogenic strains. Interestingly, after almost two decades of exhaustive preclinical evaluations, AuNPs are gradually progressively moving ahead toward clinical evaluations. However, the mechanistic aspects of the antibacterial action of AuNPs remain an unsolved puzzle for the scientific fraternity. Thus, the review covers state-of-the-art investigations pertaining to the efficacy of AuNPs as a tool to overcome ESBLs acquired resistance, their applicability and toxicity perspectives, and the revelation of the most appropriate proposed mechanism of action. Conclusively, the trend suggested that antibiotic-loaded AuNPs could be developed into a promising interventional strategy to limit and overcome the concerns of antibiotic-resistance. Full article

Obesity and vitamin D deficiency are two major public health concerns. Evidence suggests that alteration in gut microbiota composition is a possible risk factor for obesity. Additionally, altered vitamin D status has a potential role in shaping the gut microbial community. Further, the prevalence of obesity has been rising in the Middle East, especially among women of reproductive age, which is of specific concern due to its adverse effects on the health of their offspring. To date, limited evidence is available on the association between gut microbiota composition and vitamin D levels in Arab women. This study aims to identify the associations between serum vitamin D, gut microbiota, and obesity among Saudi females. The current study is a case–control study including 92 women aged 18 to 25 years, (n = 48) with normal weight and (n = 44) with obesity. Anthropometric, biochemical, lifestyle data, and fecal samples were collected and analyzed. We used shotgun metagenomic sequencing to characterize microbial communities of stool samples. Vitamin D levels were significantly associated with alpha and beta diversities. Serum vitamin D levels were positively associated with bacteria known to regulate immunological responses; Bacteroides thetaiotaomicron in the normal weight group (r = 0.34, p = 0.03) and Bifidobacterium adolescentis in the obesity group (r = 0.33, p = 0.04). In conclusion, the findings suggest that vitamin D status may play a role in regulating the gut microbiota composition by inhibiting the growth of pathogenic bacteria while nourishing the beneficial strains. Full article

Infections caused by resistant bacterial pathogens have increased the complications of clinicians worldwide. The quest for effective antibacterial agents against resistant pathogens has prompted researchers to develop new classes of antibiotics. Unfortunately, pathogens have acted more smartly by developing resistance to even the newest class of antibiotics with time. The culture sensitivity analysis of the clinical samples revealed that pathogens are gaining resistance toward the new generations of cephalosporins at a very fast rate globally. The current study developed gold nanoparticles (AuNPs) that could efficiently deliver the 2nd (cefotetan-CT) and 3rd (cefixime-CX) generation cephalosporins to resistant clinical pathogens. In fact, both CT and CX were used to reduce and stabilize AuNPs by applying a one-pot synthesis approach, and their characterization was performed via spectrophotometry, dynamic light scattering and electron microscopy. Moreover, the synthesized AuNPs were tested against uro-pathogenic resistant clinical strains of Escherichia coli and Klebsiella pneumoniae. CT-AuNPs characteristic SPR peak was observed at 542 nm, and CX-AuNPs showed the same at 522 nm. The stability measurement showed ζ potential as −24.9 mV and −25.2 mV for CT-AuNPs and CX-AuNPs, respectively. Scanning electron microscopy revealed the spherical shape of both the AuNPs, whereas, the size by transmission electron microscopy for CT-AuNPs and CX-AuNPs were estimated to be 45 ± 19 nm and 35 ± 17 nm, respectively. Importantly, once loaded onto AuNPs, both the cephalosporin antibiotics become extremely potent against the resistant strains of E. coli and K. pneumoniae with MIC₅₀ in the range of 0.5 to 0.8 μg/mL. The findings propose that old-generation unresponsive antibiotics could be revived into potent nano-antibiotics via AuNPs. Thus, investing efforts, intellect, time and funds for a nano-antibiotic strategy might be a better approach to overcome resistance than investing the same in the development of newer antibiotic molecule(s). Full article

Diabetes mellitus (DM) is a major health issue in Saudi Arabia. Prevention of DM and its complications requires an understanding of the disease and modifiable behaviors (e.g., physical activity—PA). The purpose of this study was to examine the trends in knowledge of the general population regarding DM to better understand the shortcomings in the current awareness programs. This article presents a cross-sectional series study where a survey was distributed to a total of 3493 participants over four years, from 2017 till 2020, to assess general knowledge about DM, including information about PA. The mean percentage of correct responses of DM general knowledge was 63.8 ± 19.0 in 2017, which decreased to 61.3 ± 18.7 in 2020 with a significant beta coefficient of −0.8 ± 0.2 (p < 0.001). Participants’ awareness about PA remained constantly high for four years: the mean percentage of correct responses was 82.1 ± 23.6 in 2017 and 82.0 ± 23.1 in 2020, and the beta coefficient was −0.5 ± 0.3 (p = 0.147). Furthermore, stratification by demographics showed that the majority of the subgroups (age, sex, educational status, marital status, having relative with DM, nationality) reported a significant declining trend in general DM knowledge. In addition, some of the subgroups also showed a declining trend in PA awareness. Future prevention efforts should assess the community’s DM knowledge regularly to tailor awareness efforts to the population segments that need heightened educational interventions. Full article

Nutrition-acquired osteomalacia is a bone mineralization disorder associated with dietary calcium and/or solar vitamin D deficiency, risk factors considered common in the Middle Eastern region. Establishing less invasive, cheap, and widely available diagnostic markers for this underdiagnosed entity is essential, in particular for screening in high-risk groups. This study assessed the prevalence of biochemical osteomalacia in Arab adolescents. In this cross-sectional study performed between September 2019 and March 2021, adolescents aged 12–17 years from 60 different secondary and preparatory year schools in Riyadh, Saudi Arabia were included. Anthropometrics and fasting blood samples were collected. Biochemical osteomalacia was defined as any two of the following four serum markers of hypomineralization, namely low 25 hydroxyvitamin D (25OHD < 30 nmol/L), high alkaline phosphatase (ALP), low calcium (Ca), and/or inorganic phosphorous (Pi). A total of 2938 Arab adolescents [1697 girls; mean age (years) 14.8 ± 1.8; 1241 boys; mean age 15.1 ± 1.6] were recruited. Vitamin D deficiency was noted in 56.2% (n = 953) of girls and 27.1% (n = 336) of boys (p < 0.001). The overall prevalence of biochemical osteomalacia was 10.0% (n = 295/2938) and was higher in girls than boys (14.7% vs. 3.6%, p < 0.001). The prevalence of low serum Ca and/or Pi was also higher in girls than in boys (24.2% vs. 12.5%, respectively, p < 0.001), as well as elevated ALP (5.1% vs. 1.5%, p < 0.001). Overall, girls were 4.6 times (95% CI 3.3–6.4) more likely to have biochemical osteomalacia than boys. Screening of apparently healthy Arab adolescents revealed a high prevalence of deranged mineralization markers suggestive of biochemical osteomalacia, which was significantly more common in girls than boys and was likely associated with Arab traditional clothing and diet. The proposed combination of typically altered mineralization markers for the diagnosis of osteomalacia is, at best, suggestive until further comparisons with established diagnostic tools (histological analysis of bone biopsies) are conducted. Full article

Previous studies have suggested that dietary habits and dysbiosis of gut microbiota contributed to obesity development. Vitamin B12 is produced by microbes; however, the relationships between vitamin B12, gut microbiome, and obesity are understudied. We aimed to determine the association between vitamin B12 status and gut microbiota relative to obesity in 92 Saudi Arabian females aged 19–25 years who were obese (n = 44) or normal weight (n = 48). Anthropometric, biochemical data, and dietary data were collected. The microbial communities of stool samples were characterized using the shotgun metagenomic sequencing technique. The relationship between vitamin B12 status and gut microbiota composition was identified using Pearson correlation analysis. A statistically significant difference was found in bacterial α- and β-diversity between the groups relative to median serum vitamin B12 level (404.0 pg/mL) and body weight. In the total participants, dietary vitamin B12 intake was inversely correlated with Bifidobacterium kashiwanohense and Blautia wexlerae species. In obese participants, dietary vitamin B12 intake was inversely correlated with Akkermansia muciniphila species and species from the Verrucomicrobia phylum, whereas it was positively correlated with Bacteroides species. Our findings indicate that the abundance (frequency) and diversity (richness) of gut microbiota are associated with vitamin B12 levels and obesity in young females. Full article

Breast cancer represents the most frequently occurring cancer globally among women. As per the recent report of the World Health Organization (WHO), it was documented that by the end of the year 2020, approximately 7.8 million females were positively diagnosed with breast cancer and in 2020 alone, 685,000 casualties were documented due to breast cancer. The use of standard chemotherapeutics includes the frontline treatment option for patients; however, the concomitant side effects represent a major obstacle for their usage. Carbazole alkaloids are one such group of naturally-occurring bioactive compounds belonging to the Rutaceae family. Among the various carbazole alkaloids, 3-Methoxy carbazole or C₁₃H₁₁NO (MHC) is obtained from Clausena heptaphylla as well as from Clausena indica. In this study, MHC was investigated for its anti-breast cancer activity based on molecular interactions with specific proteins related to breast cancer, where the MHC had predicted binding affinities for NF-κB with −8.3 kcal/mol. Furthermore, to evaluate the biological activity of MHC, we studied its in vitro cytotoxic effects on MCF-7 cells. This alkaloid showed significant inhibitory effects and induced apoptosis, as evidenced by enhanced caspase activities and the cellular generation of ROS. It was observed that a treatment with MHC inhibited the gene expression of NF-kB in MCF-7 breast cancer cells. These results suggest that MHC could be a promising medical plant for breast cancer treatment. Further studies are needed to understand the molecular mechanisms behind the anticancer action of MHC. Full article

Inflammatory breast cancer (IBC) is one of the most belligerent types of breast cancer. While various modalities exist in managing/treating IBC, drug delivery using microneedles (MNs) is considered to be the most innovative method of localized delivery of anti-cancer agents. Localized drug delivery helps to treat IBC could limit their adverse reactions. MNs are nothing but small needle like structures that cause little or no pain at the site of administration for drug delivery via layers of the skin. The polyethylene glycol diacrylate (PEGDA) based MNs were fabricated by using three dimensional (3D) technology called Projection Micro-Stereo Lithography (PµSL). The fabricated microneedle patches (MNPs) were characterized and coated with a coating formulation comprising of gemcitabine and sodium carboxymethyl cellulose by a novel and inventive screen plate method. The drug coated MNPs were characterized by various instrumental methods of analysis and release profile studies were carried out using Franz diffusion cell. Coat-and-poke strategy was employed in administering the drug coated MNPs. Overall, the methods employed in the present study not only help in obtaining MNPs with accurate dimensions but also help in obtaining uniformly drug coated MNPs of gemcitabine for treatment of IBC. Most importantly, 100% drug release was achieved within the first one hour only. Full article

Cucurbitacin-B (Cur-B) is an analogue triterpenoid belonging to the Cucurbitaceae family. Previous reports have explicitly outlined various biological activities of Cucurbitaceae family members, including the anticancer activity of Cur-B. In the present study, we tried to elucidate the anticancer efficacy of Cur-B against prostate cancer PC3 cells. PC3 cells were exposed to purified Cur-B at 5, 10, 15, 20 and 25 µM for 24. Cur-B exposure reduced cell viability of PC3 cells at 5 µM (p < 0.05), with further reduction with increased Cur-B concentration (15 µM, p < 0.01 and 25 µM, p < 0.001). Cur-B also succeeded in instigating nuclear fragmentation and condensation, followed by activation of caspase-8, -9 and -3 proportionally with increasing concentrations of Cur-B. Treatment with Cur-B also instigated ROS-mediated oxidative stress both qualitatively and quantitatively at 5 µM, p < 0.05; 15 µM, p < 0.01 and 25 µM, p < 0.001. Increased ROS after Cur-B treatment also led to dissipation of mitochondrial membrane potential, thereby resulting in considerable apoptosis (p < 0.001), which, again, was proportionally dependent on Cur-B concentration. Cur-B exposure to PC3 cells was concomitantly followed by reduced cyclin D1, cyclin-dependent kinase 4 (CDK4) expression and augmented mRNA expression of CDK inhibitor p21^Cip1. Intriguingly, Cur-B exposure also led to considerable downregulation of the JAK/STAT signaling cascade, which may be the reason behind Cur-B-mediated apoptosis and cell cycle arrest within PC3 cells. Therefore, these observations explicitly establish that Cur-B could serve in the prevention of prostate cancer. Full article