Safety and efficacy of stem cell therapy for Crohn's disease: An umbrella review of systematic reviews.

BACKGROUND: Crohn's disease is a chronic, relapsing form of inflammatory bowel disease marked by severe gastrointestinal inflammation and a broad range of debilitating symptoms. Despite advances in medical treatments, achieving sustained remission remains challenging for many patients. This umbrella review aims to consolidate evidence from various systematic reviews to evaluate the efficacy and safety of stem cell therapies in treating Crohn's disease. METHODS: This review followed the Joanna Briggs Institute methodology and adhered to PRISMA guidelines. A literature search of PubMed, Web of Science, Embase, and the Cochrane Library covered records up to April 20, 2024. Only systematic reviews and meta-analyses on stem cell therapy for Crohn's disease were considered. Data were extracted and analyzed for clinical efficacy indicators like remission induction and safety metrics, including adverse events and mortality rates. RESULTS: Sixteen systematic reviews were included, spanning studies conducted between 2009 and 2023. Stem cell therapy showed a pooled risk ratio (RR) of 1.299 (95% CI: 1.192 to 1.420) for clinical remission, indicating a 29.9% increased likelihood of remission compared to controls. The pooled RR for healing perianal Crohn's disease was 1.358 (95% CI: 1.13 to 1.631), suggesting a 35.8% increased likelihood of healing. A pooled RR of 1.481 (95% CI: 1.036 to 2.116) shows a 48.1% higher immediate fistula closure rate with stem cell therapy. For long-term outcomes, a RR of 1.422 (95% CI: 1.091 to 1.854) indicates a 42.2% increased likelihood of maintaining closure. However, stem cell therapy did not significantly impact Crohn's Disease Activity Index (CDAI) (RR: 1.154, 95% CI: 0.193 to 6.883) and Perianal Disease Activity Index (PDAI) scores (mean difference at 12 weeks: -0.505, 95% CI: -2.481 to 1.471; mean difference at 24 weeks: -0.338, 95% CI: -1.638 to 0.963). The safety profile was comparable to conventional therapies, with a pooled RR of 0.972 (95% CI: 0.739 to 1.278) for adverse events and 1.136 (95% CI: 0.821 to 1.572) for serious adverse events. CONCLUSION: Stem cell therapy offers significant progress in treating Crohn's disease, particularly in complex cases, by improving fistula closure rates and suggesting potential as a supplementary therapy. Its safety profile aligns with conventional treatments, yet ongoing clinical trials are crucial to optimize its use. Continual research will enable healthcare providers to tailor more effective treatment strategies for this challenging condition.

Cetuximab-conjugated sodium selenite nanoparticles for doxorubicin targeted delivery against MCF-7 breast cancer cells.

Aim: To develop and characterize doxorubicin-loaded sodium selenite nanoparticles (SSNP-DOX) and their surface attachment with cetuximab (mAb-SSNP-DOX).Methods: SSNP-DOX was formulated by gelation and then conjugated with cetuximab to form mAb-SSNP-DOX. Characterization included DLS, SEM, TEM, DSC, Raman spectroscopy and XRD. In vitro, the kinetics of doxorubicin release and cytotoxicity in MCF-7 breast cancer cells were investigated.Results: The zeta potential for SSNP-DOX and mAb-SSNP-DOX was -14.4 ± 10.1 mV and -27.5 ± 7.28 mV, with particle sizes of 181.3 nm and 227.5 nm, respectively. The formulation intensity was 89.7% for SSNP-DOX and 100% for mAb-SSNP-DOX, with PDI values of 0.419 and 0.251, respectively. SEM and TEM showed that mAb-SSNP-DOX was smooth and spherical. The DSC analysis revealed exothermic peaks at 102.44°C for SSNP-DOX and 144.21°C for mAb-SSNP-DOX, along with endothermic peaks at 269.19°C and 241.6°C, respectively. Raman spectroscopy showed a higher intensity for mAb-SSNP-DOX. The XRD study showed different peaks for each formulation. Both followed zero order kinetics for doxorubicin release. Cytotoxicity studies showed significant effects and high apoptosis in MCF-7 cells for both formulations.Conclusion: The mAb-SSNP-DOX showed promising properties, more effective doxorubicin release and higher cytotoxicity against breast cancer cells compared with SSNP-DOX.

[Box: see text].

Coffee arabica research (1932-2023): Performance, thematic evolution and mapping, global landscape, and emerging trends.

Background: Research on Coffea arabica focuses on various aspects, including genetics, breeding, climate change resilience, pest and disease management, agronomy, sensory analysis, and sustainability. This study aims to analyze the hotspots, conceptual map and dynamicity, global landscape, and emerging trends in Coffea arabica research (CA-R). Methods: A comprehensive dataset comprising data-driven articles (N = 3967) from 1932 to 2023 was extracted from Scopus using predefined search terms. VOSviewer and Bibliometrix applications were utilized to analyze the data. Thematic evolution was examined by identifying shifts in research focus over time. The global landscape was assessed by examining comparative productivity and collaborative dynamics. Highly-cited CA-R was identified to highlight key findings in specific research areas. Results: The analysis revealed a steady growth of CA-R (annual growth rate = 6.53 %), with strong international collaboration (international co-authorships = 29.35 %) and significant contributions from various countries. Brazil leads the way with 1601 publications, accounting for 28.55 % of the total. Recognizable CA-R focused on important areas such as pollination, shade management, nanotechnology applications, roasting effects, disease management, and environmental impacts. Thematic analysis identified five distinct clusters representing different CA-R themes: "coffee", "coffea," "fermentation," "Coffea arabica," and "climate change." Emerging themes such as "in vitro culture," "sustainable agriculture," "climate change," and "coffee berry borer" were also identified. Conclusion: The current findings enhance our understanding of CA-R and lay the groundwork for future studies in the coffee industry.

Robotic surgery: bibliometric analysis, continental distribution, and co-words analysis from 2001 to 2023.

The project aimed to conduct an up-to-date and comprehensive bibliometric analysis of robotic surgery to provide a detailed and holistic understanding of the field. Three strategies were employed in the data analysis i.e. search terms were explored in (A) the title, abstract, and keywords and (B) only in the title of the documents. In 3rd part we analyzed the top 100 most cited papers. Vosviewer and R Studio were utilized for detailed bibliometric and network analyses. Strategy one identified 38,469 publications, and strategy two identified 6451 publications from 2001 to 2023. The top authors, universities, countries, sponsors, and sources based on the number of publications were identified for both strategies. The top 100 most cited papers were analyzed, providing the annual number of publications and various citation metrics. Top authors (by number of publications, total citations, h-index, g-index, and m-index), universities, and countries within these highly cited papers, along with their co-authorship networks and dynamics, were examined. Co-words analysis of the top 100 most cited papers revealed the primary focus of these documents across 25 categories. This comprehensive bibliometric analysis of robotic surgery highlighted significant contributions and collaborations in the field, emphasizing the importance of global and collaborative efforts in advancing robotic surgery research.

Top 1000 Most Cited Papers in World Neurosurgery.

BACKGROUND: Over the past 15 years, WORLD NEUROSURGERY (WN) has emerged as a pivotal source in the neurosurgery field, reflecting remarkable growth and development. Originally published as Surgical Neurology from 1973 to 2009, the journal transitioned to its current title in 2010, significantly expanding its reach and influence. METHODS: A comprehensive bibliometric analysis of WN's publications from 1973 to 2023 was performed. The analysis focused on identifying the top authors, universities, countries, and sponsors in 2 periods: 1973-2009 and 2010-2023. Additionally, the study included a detailed examination of the top 1000 most cited papers, and summary of top 10 most cited papers. RESULTS: The analysis revealed that during the Surgical Neurology period, 6567 research documents were published, including 6503 articles and 64 reviews. Since rebranding as WN, the journal has published an additional 17,663 documents, comprising 15,366 articles and 2297 reviews up to 2023. The top contributors (authors, universities, and sponsors) were identified, and the study found that WN has successfully increased its foothold across various continents. The co-word analysis provided insights into the thematic focus of the top 1000 most cited papers, categorizing them into 15 distinct areas. CONCLUSIONS: This study underscores WN's significant role in advancing neurosurgical research over the past 5 null decades. The findings highlight the journal's evolution, its expanding global influence, and the key contributors to its success.

Bibliometric Analysis of Machine Learning Applications in Ischemia Research.

OBJECTIVE: The objective of this study is to conduct a comprehensive bibliometric analysis to elucidate the landscape of machine learning applications in ischemia research. METHODS: The analysis can be divided in three sections: part 1 scrutinizes articles and reviews with "ischemia" in their titles, while part 2 further narrows the focus to publications containing both "ischemia" and "machine learning" in their titles. Additionally, part 3 delves into the examination of the top 50 most cited papers, exploring their thematic focus and co-word dynamics. RESULTS: The findings reveal a significant increase in publications over the years, with notable trends identified through detailed analysis. The growth in publication counts over time, the leading contributors, institutions, geographical distribution of research output and journals are numerically presented for part 1 and part 2. For the top 50 most cited papers the dynamics of co-words, which offer a nuanced understanding of thematic trends and emerging concepts, are presented. Based on the number of citations the top 10 authors were selected, and later for each, total number of publications, h-index, g-index and m-index are provided. Additionally, figures depicting the co-authorship network among authors, departments, and countries involved in the top 50 cited papers may enrich our comprehension of collaborative networks in ischemia research. CONCLUSION: This comprehensive bibliometric analysis provides valuable insights into the evolving landscape of machine learning applications in ischemia research.

Risk of acute coronary syndrome and relationship with the use of khat and tobacco products in the Jazan region, Saudi Arabia: A prospective case-control study.

INTRODUCTION: Previous studies have identified several risk factors for acute coronary syndrome (ACS). This study was intended to examine the potential risk of ACS associated with khat and tobacco use. METHODS: A case-control study of 344 people (172 cases and 172 controls) was conducted at Prince Mohammed Bin Nasser Hospital in Jazan, Saudi Arabia, from April to September 2019. The cases and controls were matched for age (±5 years) and gender. Data were analyzed using descriptive, inferential, and modeling analyses. We utilized the adjusted odds ratio (AOR) to express the results. RESULTS: The prevalence of ever khat chewing among all study participants was 29.1%, significantly higher for the cases with ACS than for the control group (43.6% vs 14.5%, p<0.001). Cigarette smokers accounted for 33.4% of the study participants, and 22.1% were ACS cases, which is a significantly higher percentage than the control group. The prevalence of smokeless tobacco was 20.3% among ACS cases and 14.5% among controls, with no statistically significant differences (p>0.05). In the final model, tobacco use was more likely to be reported among cases with myocardial infarction (MI) (AOR=4.58; 95% CI: 1.01-4.73, p<0.05) as was khat chewing (AOR=3.4; 95% CI: 1.55-7.46, p<0.05), after controlling for other traditional risk factors. CONCLUSIONS: Khat chewing was reported more by those who reported ACS. ACS cases were more likely to be frequent khat users with chewing sessions of five or more days per week. Regular tobacco use was also reported in those who reported ACS, and this increases with the amount of tobacco used. Implementing early intervention strategies can help mitigate the impact of khat chewing and smoking on the development of ACS.

Evaluation of Biochemical Characteristics in a Retrospective Cohort of COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had a significant impact on global health and healthcare systems. This retrospective study aimed to assess the association between biochemical parameters and outcomes in COVID-19 patients in Jazan, Saudi Arabia. METHODS: After establishing the inclusion criteria and obtaining ethical approval, data from 156 reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients were collected from electronic medical records from a general hospital in Samtah, Jazan, from April 2020 to October 2021. The collected data included patient demographics and liver, kidney, heart, and electrolyte function marker levels. Descriptive, inferential, and principal component analyses were conducted. RESULTS: Survival rates varied according to age and body mass index (BMI). Statistical analysis demonstrated that the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), creatine kinase (CK), CK myocardial band (MB), and lactate dehydrogenase (LDH) were significantly higher (P < 0.05) than the reference values, as assessed using the one-sample t-test. Principal component analysis (PCA) also revealed an underlying pattern in the variation of these biochemical markers. These findings suggest that certain biochemical parameters may serve as useful indicators for monitoring the condition of COVID-19 patients. CONCLUSION: This retrospective study in Jazan, Saudi Arabia highlights the association between biochemical parameters and outcomes in COVID-19 patients. Elevated levels of markers of liver, kidney, heart, and electrolyte function suggest organ damage and dysregulation. The pattern identified through PCA provides insights into disease severity. Monitoring these parameters may serve as valuable indicators for assessing COVID-19 patients. Further research is needed to validate these findings, explore their potential for personalized treatment strategies, and improve patient outcomes during the ongoing pandemic.

Cancer research in the United Arab Emirates from birth to present: A bibliometric analysis.

Background: Accumulating evidence indicates that the incidence of cancer is increasing in the United Arab Emirates (UAE). This analysis aimed to determine the current cancer research output in the UAE to guide future national research. Methods: The Scopus database was searched for cancer-related bibliographic data from the UAE. The number of publications, citation analysis, co-authorship of the author, institution, and country, keyword co-occurrence, and reference co-citations were analyzed using the R-studio bibliometrics package and VOSviewer software. Results: A total of 1678 journal articles were retrieved from 1981 to 2022. Cancer research in the UAE (UCR) is increasing at a rate of 14.64% (R-squared = 0.75; F = 46.477; P<0.001). The UAE had a 0.06% participation rate in terms of the number of original articles. The rate of international co-authorship is 40.23%. The U.S.A., U.K., Egypt, Saudi Arabia, India, and Canada had more than 100 co-authored documents from 156 countries that collaborated with the U.A.E. Conclusions: Compared to other nations, the UAE has fewer publications on cancer, although the number is growing. The current report provides an up-to-date and in-depth summary of the trends in UCR. This project is an excellent place for researchers interested in conducting data-mapping work in this field.

Association of genetic predisposition studies in CYP1A1 polymorphism studies in acute myeloid leukemia.

Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) gene is one of the sub-members of CYP450 family member and it encodes with the families of drug metabolizing enzyme families along with the cancers and leukemias. Among leukemias, AML is considered to be one of the important leukemia which attack the older adults. The aim of this study is to explore the role of A4889G polymorphism in CYP1A1 gene in acute myeloid leukemia (AML) in the Saudi population. This study was designed as an experimental case-control study in which 100 AML cases and 100 controls were selected. This in vivo study was carried out using genomic DNA extraction, polymerase chain reaction and agarose gel electrophoresis and then BsrDI restriction enzyme to digest the A4889G polymorphism of the PCR products. In this study, 200 subjects were digested and based on the appearance of the bands, genotypes were categorized. The attained data was used to calculate the clinical details as well as genotype analysis. The study results confirmed AG genotype (OR = 3.23, CI = 1.60-6.55, p = 0.0008), AG + GG (OR = 3.47, CI = 1.76-6.86, p = 0.0002) and GG + AA (OR = 12.47, CI = 6.18-15.17, p < 0.0001) and G vs A (OR = 3.15, CI = 1.71-5.81, p = 0.0001) were associated in AML cases. In conclusion, we confirm that A4889G polymorphism is associated with AML in the Saudi population.

HDAC inhibition by Nigella sativa L. sprouts extract in hepatocellular carcinoma: an approach to study anti-cancer potential.

A wide variety of natural products have been widely used in chemoprevention therapy because they have antioxidant, anti-inflammatory, and anticancer activity. In the present study, we shed light on the 5th day germinated sprouts of N. sativa seeds and evaluated them against HDAC inhibition and antioxidant activity. The extract from the seed and sprout was extracted and characterised by LC-MS/MS, FTIR, and NMR to reveal its chemical composition, especially thymol (THY) and thymoquinone (TQ). Hepatocellular carcinoma (HCC) is a global health concern as it is a major lifestyle disease. Hence, incorporating herbal-based therapeutic compounds into everyday routines has become an attractive alternative for preventing hepatic diseases. Histone deacetylase (HDAC) inhibition (HDACi) is emerging as a promising therapeutic strategy for managing various carcinomas including HCC. Therefore, the 5th day of N. sativa can be used as a potential anticancer agent by inhibiting HDAC activity, as it is reported to have an important role in the management of oxidative stress. The bioactive compound of N. sativa, i.e. thymoquinone, also showed a good binding affinity with the HDAC protein (3MAX) with a stable interaction in an in silico study as compared to the standard drug (Trichostatin A) and thymol.Communicated by Ramaswamy H. Sarma.

A case-control study in NAT2 gene polymorphism studies in patients diagnosed with acute myeloid leukemia.

INTRODUCTION: Acute myeloid leukemia (AML) is a clinically defined heterogeneous disease whose pathophysiology is currently unknown. The association of NAT2 acetylation profiles with human cancer risks, particularly with AML, was investigated in molecular epidemiological studies. Additionally, the NAT2 gene was carried out with acute lymphoid leukemia and other cancers. AIM: In this case-control study, C481T (rs1799929) and G857A (rs1799931) polymorphism studies were investigated in diagnosed AML patients in the Saudi population. METHODS: This case-control study included 100 AML patients and 100 control subjects recruited in Saudi Arabia. The C481T and G857A polymorphisms were genotyped using specific primers and restriction enzymes. Statistical analysis was performed on the AML patients and controls using chi-square tests, genotyping, and allele frequencies (odds ratios, 95% of confidence intervals, and P-values). RESULTS: Hardy Weinberg Equilibrium was determined to be both within and outside of the G857A and C481T polymorphisms. The allele and genotyping frequencies in AML and control subjects were analyzed, and the results corroborated the unfavorable connection with C481T (CC vs CT+TT; OR-1.12; (95% CIs: 0.64-1.96); P=0.67 and T vs C; OR-0.89; (95% CIs: 0.59-1.35) and P=0.60) and G857A polymorphisms (GG vs GA+AA; OR-1.50; (95% CIs: 0.83-2.71); P=0.17 and A vs G; OR-0.71; (95%CIs: 0.43-1.19) and P=0.19) in the NAT2 gene. CONCLUSION: The study results revealed a negative correlation as well as a protective factor for AML with the C481T and G857A polymorphisms in the NAT2 gene.

The sub-acute toxicity of kavalactone in rats: a study of the effect of oral doses and the mechanism of toxicity in combination with ethanol.

Kava is a herbal supplement and beverage made from the Piper methysticum plant, which is known for its recreational use as a mood enhancer, relaxation, as well as pain relief for centuries. Kava is widely used among alcoholics, but it is dangerous and potentially fatal. The objectives of this study were to examine the sub-acute toxicity effects of different doses of 70% kavalactone (KL) in rats by oral application, as well as to elucidate the mechanisms of toxicity alone and in combination with ethanol (EtOH). The most common side effects observed were abnormal breathing, ataxia, lethargy, loss of appetite, indigestion, and loss of coordination, especially in the 800 mg/kg bw, po bodyweight dosage of kava treatment group alone, and in combination with EtOH. In the sub-acute study, there were dose-related decreases in body weight, feed intake, and water consumption rates. Gross and histopathological findings revealed that the liver was abnormal in color, size, consistency, and the weight significantly increased at a dose of 800 mg/kg bw, po, with KL alone and a greater increase in combination with EtOH. Hepatocellular hypertrophy (HP) and necrosis with Kupffer cells hyperplasia were observed in the periacinar zone of all rats dosed with KL (800 mg/kg bw, po) alone, and extensive changes were observed in combination with EtOH. The periportal (Z1) and mid-zonal (Z2) areas of hepatocytes were less affected as compared to the periacinar zone. These results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity. The histopathological results supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner.

Cancer of the Liver and its Relationship with Diabetes mellitus.

A high increase witnessed in type II diabetes mellitus (T2DM) globally has increasingly posed a serious threat to global increases in liver cancer with the association between diabetes mellitus type II and the survival rate in liver cancer patients showing unstable findings. An increase in the development and progression of chronic liver disease from diabetes mellitus patients may be connected to cancer of the liver with several links such as Hepatitis B and C virus and heavy consumption of alcohol. The link between T2DM patients and liver cancer is centered on non-alcoholic fatty liver disease (NAFLD) which could be a serious threat globally if not clinically addressed. Several reports identified metformin treatment as linked to a lower risk of liver cancer prognosis while insulin treatment or sulphonylureas posed a serious threat. Mechanistically, the biological linkage between diabetes type II mellitus and liver cancer are still complex to understand with only the existence of a relationship between NAFLD and high level of energy intake and diabetes mellitus induces hepatic damage, increased liver weight thereby causes multiple pro-inflammatory cytokines that lead to the development of liver cancer. Therefore, this review gives an account of the pathophysiological importance of liver cancer position with T2DM, with the role of NAFLD as an important factor that bridges them.

Zingiber officinale and Vernonia amygdalina Infusions Improve Redox Status in Rat Brain.

The study investigated the effects of Zingiber officinale root and Vernonia amygdalina leaf on the brain redox status of Wistar rats. Twenty-four (24) rats weighing 160 ± 20 g were randomly assigned into four (4) groups, each with six (6) rats. Animals in Group 1 (control) were orally administered distilled water (1 mL), while the test groups were orally administered 5 mg/mL of either Z. officinale, V. amygdalina infusion, or a combination of both, respectively, for 7 days. The rats were sacrificed at the end of treatments and blood and tissue were harvested and prepared for biochemical assays. Results showed that administration of V. amygdalina and Z. officinale, as well as their coadministration, reduced the levels of malondialdehyde (MDA), nitric oxide (NO), acetylcholinesterase (AChE), and myeloperoxidase (MPO) in rat brain tissue compared with the control group. Conversely, coadministration of V. amygdalina and Z. officinale increased the levels of reduced glutathione (GSH) in rat brain tissue compared with the control group. However, the administration of the infusions singly, as well as the combination of both infusions, did not have any effect on the rat brain levels of glutathione peroxidase (GPx) and catalase (CAT) antioxidant enzymes compared to the control. Taken together, the findings indicate that the V. amygdalina and Z. officinale tea infusions have favorable antioxidant properties in the rat brain. The findings are confirmatory and contribute to deepening our understanding of the health-promoting effects of V. amygdalina and Z. officinale tea infusions.

Monkeypox virus: Future role in Human population.

BACKGROUND: Monkeypox viral infection is considered as global public health and a rare disease caused by Monkeypox virus (MPXV), which is caused by smallpox-like virus and it causes pustules all over the body. MPV is an emerging zoonotic infection with sporadic occurrence globally and multiple outbreaks have been reported in African regions. The story of MPXV has been started since 1970 in Democratic republic of Cargo. The high cases of MPXV was majorly detected in Congo Rain Forest region in Africa. Animal-human (Zoonotic) transmission occurred, although the individual infected animal was not recognized. Human-human transmission occurs and is difficult until bodily fluids or respiratory droplets are exchanged. If a specific individual uses an infected person's towels or bed sheets, infection may occur. AIM: The aim of this review is to document the methods of diagnosis, treatments (vaccines) and future role of MPXV in human population. OUTPUT: The diagnosis is confirmed mainly through clinical diagnosis and then laboratory diagnosis such as cell-culture, serological and Polymerase Chain Reaction tests. Presently, there is no vaccine for MPXV but the smallpox vaccine will protect. The old vaccine includes antivirals approved for use against Orthopoxvirus, such as tecovirimat, which can treat up to 85 % of MPXV in humans. MPXV is now considered as transmission virus which affects from human to humans. The fatality rate was documented to be 3-10 % in children and in adults it is very low. CONCLUSION: This review concludes MPXV is not as contagious as COVID-19 but proper measures should be taken as mentioned in this review to avoid MPXV. Presently, controlling MPXV presents unique challenges, and future prospective global studies in antivirals for this disease, as well as an MPXV vaccines, are recommended to eliminate this virus.

Elucidating the Neuroprotective Effect of Tecoma stans Leaf Extract in STZ-Induced Diabetic Neuropathy.

Background: Diabetes is considered one of the most encyclopedic metabolic disorders owing to an alarming rise in the number of patients, which is increasing at an exponential rate. With the current therapeutics, which only aims to provide symptomatic and momentary relief, the scientists are shifting gears to explore alternative therapies which not only can target diabetes but can also help in limiting the progression of diabetic complications including diabetic neuropathy (DN). Methods: Tecoma stans leaf methanolic extract was prepared using the Soxhlet method. A streptozotocin (STZ; 45 mg/kg)-induced diabetic animal model was used and treatment with oral dosing of T. stans leaf extract at the different doses of 200 mg/kg, 300 mg/kg, and highest dose, i.e., 400 mg/kg, was initiated on day 3 after STZ administration. The pharmacological response for general and biochemical (angiogenic, inflammatory, and oxidative) parameters and behavioral parameters were compared using Gabapentin as a standard drug with the results from the test drug. Results: Parameters associated with the pathogenesis of diabetic neuropathy were evaluated. For general parameters, different doses of T. stans extract (TSE) on blood sugar showed significant effects as compared to the diabetic group. Also, the results from biochemical analysis and behavioral parameters showed significant positive effects in line with general parameters. The combination therapy of TSE at 400 mg/kg with a standard drug produced nonsignificant effects in comparison with the normal group. Conclusion: The leaves of T. stans possess antidiabetic effects along with promising effects in the management of DN by producing significant effects by exhibiting antioxidative, antiangiogenic, and anti-inflammatory properties, which are prognostic markers for DN, and thus, T. stans can be considered as an emerging therapeutic option for DN.

In Silico Identification of Hub Genes as Observing Biomarkers for Gastric Cancer Metastasis.

Perception of hub genes engaged in metastatic gastric cancer (mGC) promotes novel ways to diagnose and treat the illness. The goal of this investigation is to recognize the hub genes and reveal its molecular mechanism. In order to explore the potential facts for gastric cancer, the expression profiles of two different datasets were used (GSE161533 and GSE54129). The genes were confirmed to be part of the PPI network for gastric cancer pathogenesis and prognosis. In Cytoscape, the CytoHubba module was used to discover the hub genes. Responsible hub genes were identified. Data from Kaplan-Meier plotter confirmed the predictive value of these distinct genes in various stages of gastric malignancy. Upregulated and downregulated genes were identified to utilize for further analysis. Positive regulation by a host of viral process, positive regulation of granulocyte differentiation, negative regulation of histone H3-K9 methylation were found in DEGs analysis. In addition, five KEGG pathways were identified as an essential enhancer that include nucleotide excision repair; base excision repair; DNA replication; homologous recombination; and complement and coagulation cascades. POLE, BUB1B, POLD4, C3, BLM, CCT7, PRPF31, APEX1, PSMA7, and CDC45 were chosen as hub genes after combining the PPI results. Our study recommends that BUB1B, CCT7, APEX1, PSMA7, and CDC45 might be potential biomarkers for gastric cancer. These biomarkers are upregulated genes. Therefore, suppression of these genes will increase the survival rate in gastric cancer patients.

Screening of V617F mutation in JAK2 gene with acute myeloid leukemia in the Saudi population.

Progress in pathogenesis and therapy of acute myeloid leukemia (AML) is presently accelerating. The Janus kinase 2 gene (JAK2) mutations are rare in de novo AML. The gene codes for the tyrosine kinase that has a significant role in the signal transduction in hematopoietic cells. The aim of this study was to induce V617F mutation in the JAK2 gene in the AML patients diagnosed in the Saudi population. In this case-control study, 100 AML patients and 100 healthy controls were recruited. Genotyping was performed with polymerase chain reaction followed with restriction fragment length polymorphism analysis. The mean age of the AML patients and healthy controls was found to be almost similar (p=0.60). In this study, 15% of VF mutation was documented in the AML cases and none of the mutations were documented either in FF mutation in AML cases or VF and FF mutations in the healthy control subjects. VF mutations [VF vs VV; OR-18.79; (95%CIs: 2.442-144.6) and p=0.0001; F vs V; OR-87.76; (95% CIs: 11.76-654.7) and p<0.0001] were found to be significantly associated when compared between AML cases and healthy controls. In conclusion, the V617F mutation showed the positive association in the AML patients diagnosed in the Saudi population.

Curcumin-Based Inhibitors of Thrombosis and Cancer Metastasis Promoting Factor CLEC 2 from Traditional Medicinal Species Curcuma longa.

The CLEC-2 receptor protein belongs to the C-type lectin superfamily of transmembrane receptors that have one or more C-type lectin-like domains. CLEC-2 is a physiological binding receptor of podoplanin (PDPN), which is expressed on specific tumour cell types and involved in tumour cell-induced platelet aggregation and tumour metastasis. CLEC-2 and podoplanin-expressing tumour cells interact to increase angiogenesis, tumour development, and metastasis. CLEC-2 is a hemi-immunoreceptor tyrosine-based activation motif (hemi-ITAM) receptor located on platelets and a subset of dendritic cells that are expressed constitutively. This molecule is secreted by activated platelets around tumours and has been shown to inhibit platelet aggregation and tumour metastasis in colon carcinoma by binding to the surface of tumour cells. Pharmacokinetic studies were carried using a DrugLiTo, and molecular docking was performed using AutoDock Tools 1.5.6 (ADT). Twenty-nine bioactive compounds were included in the study, and four of them, namely, piperine, dihydrocurcumin, bisdemethoxycurcumin, and demothoxycurcumin, showed potential antagonist properties against the target. The resultant best bioactive was compared with commercially available standard drugs. Further, validation of respective compounds with an intensive molecular dynamics simulation was performed using Schrödinger software. To the best of our knowledge, this is the first report on major bioactive found on clove as natural antagonists for CLEC-2 computationally. To further validate the bioactive and delimit the screening process of potential drugs against CLEC-2, in vitro and in vivo studies are needed to prove their efficacy.