Prevalence of human papillomavirus in head and neck cancer patients in India: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations. METHODS: A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3). RESULTS: The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8-42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2-62.4) in the eastern regions and 19.8% (95% CI: 10.8-33.4) in the western regions. No evidence of publication bias was detected. CONCLUSION: The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.

Antiviral actions of natural compounds against dengue virus RNA dependent RNA polymerase: insights from molecular dynamics and Gibbs free energy landscape.

Dengue fever, a major global health challenge, affects nearly half the world's population and lacks effective treatments or vaccines. Addressing this, our study focused on natural compounds that potentially inhibit the dengue virus's RNA-dependent RNA polymerase (RdRp), a crucial target in the viral replication cycle. Utilizing the MTiOpenScreen webserver, we screened 1226 natural compounds from the NP-lib database. This screening identified four promising compounds ZINC000059779788, ZINC0000044404209, ZINC0000253504517 and ZINC0000253499146), each demonstrating high negative binding energies between -10.4 and -9.9 kcal/mol, indicative of strong potential as RdRp inhibitors. These compounds underwent rigorous validation through re-docking and a detailed 100 ns molecular dynamics (MD) simulation. This analysis affirmed the dynamic stability of the protein-ligand complexes, a critical factor in the effectiveness of potential drug candidates. Additionally, we conducted essential dynamics and free energy landscape calculations to understand the structural transitions in the RdRp protein upon ligand binding, providing valuable insights into the mechanism of inhibition. Our findings present these natural molecules as promising therapeutic agents against the dengue virus. By targeting the allosteric site of RdRp, these compounds offer a novel approach to hinder the viral replication process. This research significantly contributes to the search for effective anti-dengue treatments, positioning natural compounds as potential key players in dengue virus control strategies.Communicated by Ramaswamy H. Sarma.

Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). RESULT: Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5). CONCLUSION: The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.

Differentiating between early melanomas and melanocytic nevi: A state-of-the-art review.

Clinicians and dermatologists are challenged by accurate diagnosis of melanocytic lesions, due to melanoma's resemblance to benign skin conditions. Several methodologies have been proposed to diagnose melanoma, and to differentiate between a cancerous and a benign skin condition. First, the ABCD rule and Menzies method use skin lesion characteristics to interpret the condition. The 7-point checklist, 3-point checklist, and CASH algorithm are score-based methods. Each of these methods attributes a score point to the features found on the skin lesion. Furthermore, reflectance confocal microscopy (RCM), an integrated clinical and dermoscopic risk scoring system (iDscore), and a deep convoluted neural network (DCNN) also aids in diagnosis. RCM optically sections live tissues to reveal morphological and cellular structures. The skin lesion's clinical parameters determine iDscore's score point system. The DCNN model is based on a detailed learning algorithm. Therefore, we discuss the conventional and new methodologies for the identification of skin diseases. Moreover, our review attempts to provide clinicians with a comprehensible summary of the wide range of techniques that can help differentiate between early melanomas and melanocytic nevi.

Exploration of potent antiviral phytomedicines from Lauraceae family plants against SARS-CoV-2 RNA-dependent RNA polymerase.

RNA-dependent RNA polymerase, also known as RdRp, is a possible therapeutic target that could be used to suppress the proliferation of RNA viruses such as SARS-CoV-2. This protein has two major functional sites (a) catalytic and (b) substrate entry, which regulate the natural substrate entry and its corresponding interaction with the protein. In this study, a computational drug design pipeline was applied to investigate potential inhibitors against SARS-CoV-2 RdRp from Lauraceae plants, and five top hits were selected based on the docked score (< -7 kcal/mol). The docking study suggested that the Glochidioboside had a minimum binding score of -7.8 kcal/mol. This compound showed total five hydrogen bonds while two of them were with catalytic residues Asp618 and Asp760. However, another compound, Sitogluside showed a binding score of -7.3 kcal/mol with four hydrogen bonds targeting three functional residues (Arg555, Ser759, and Asp760). Later, 100 ns explicit solvent molecular dynamics (MD) simulation was performed to evaluate the stability of the protein-ligand docked system. These compounds translocated their positions from the catalytic site to the substrate entry site, as observed in the MD simulation trajectory. However, translocation did not affect the binding strength of these compounds, and they retained the strong binding affinity (ΔG < -11.5 kcal/mol), estimated using the MM/GBSA method. In general, the findings of this study indicated the potential therapeutic compounds that may be used targeting SARS-CoV-2 RdRp. However, these compounds still need to be validated by experimentation in order to determine their inhibitory function.Communicated by Ramaswamy H. Sarma.

Nephroprotective potential of Polyalthia longifolia roots against vancomycin-induced renal toxicity in experimental animals.

This study was done to investigate the possible nephroprotective effect of an ethanolic root extract of Polyalthia Longifolia (PL) on vancomycin-induced nephrotoxicity using curative and protective models. Vancomycin (150 mg/kg, intravenous) was given to healthy Wistar albino rats in the curative model before the start of treatment, whereas the protective group received vancomycin at the conclusion of the 10-day treatment procedure. Animals were divided into six groups for both models; group I served as the normal control, while groups II, III, IV, V, and VI were kept as toxic control, standard (selenium, 6 mg/kg), LDPL (low dose of PL 200 mg/kg), HDPL (high dose of PL 400 mg/kg), and HDPL + selenium (interactive) groups, respectively. Renal biomarkers [(uric acid, creatinine, blood urea nitrogen (BUN), serum proteins], and blood electrolyte levels were measured for all tested groups. When compared to the vancomycin group, the HDPL significantly (p < 0.01) showed greater effectiveness in lowering the BUN, potassium, and calcium levels. Additionally, in the curative model, there was a significant (p < 0.05) decrease in the blood levels of uric acid, creatinine, BUN, potassium, and calcium in the animals who received the combination of selenium and HDPL. Both LDPL and HDPL did not provide any distinguishable effect in the protective model, but groups that received HDPL with selenium did provide detectable protection by significantly lowering their levels of uric acid, BUN, serum potassium, and total serum protein in comparison to the vancomycin control group. These findings indicate that, whether administered before or after renal damage is induced, the Polyalthia longifolia root extract provided only modest protection to nephrons, which require selenium support to prevent vancomycin-induced kidney damage.

Application of CRISPR/Cas9 Technology in Cancer Treatment: A Future Direction.

Gene editing, especially with clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9), has advanced gene function science. Gene editing's rapid advancement has increased its medical/clinical value. Due to its great specificity and efficiency, CRISPR/Cas9 can accurately and swiftly screen the whole genome. This simplifies disease-specific gene therapy. To study tumor origins, development, and metastasis, CRISPR/Cas9 can change genomes. In recent years, tumor treatment research has increasingly employed this method. CRISPR/Cas9 can treat cancer by removing genes or correcting mutations. Numerous preliminary tumor treatment studies have been conducted in relevant fields. CRISPR/Cas9 may treat gene-level tumors. CRISPR/Cas9-based personalized and targeted medicines may shape tumor treatment. This review examines CRISPR/Cas9 for tumor therapy research, which will be helpful in providing references for future studies on the pathogenesis of malignancy and its treatment.

Artificial Intelligence for Clinical Diagnosis and Treatment of Prostate Cancer.

As medical science and technology progress towards the era of "big data", a multi-dimensional dataset pertaining to medical diagnosis and treatment is becoming accessible for mathematical modelling. However, these datasets are frequently inconsistent, noisy, and often characterized by a significant degree of redundancy. Thus, extensive data processing is widely advised to clean the dataset before feeding it into the mathematical model. In this context, Artificial intelligence (AI) techniques, including machine learning (ML) and deep learning (DL) algorithms based on artificial neural networks (ANNs) and their types, are being used to produce a precise and cross-sectional illustration of clinical data. For prostate cancer patients, datasets derived from the prostate-specific antigen (PSA), MRI-guided biopsies, genetic biomarkers, and the Gleason grading are primarily used for diagnosis, risk stratification, and patient monitoring. However, recording diagnoses and further stratifying risks based on such diagnostic data frequently involves much subjectivity. Thus, implementing an AI algorithm on a PC's diagnostic data can reduce the subjectivity of the process and assist in decision making. In addition, AI is used to cut down the processing time and help with early detection, which provides a superior outcome in critical cases of prostate cancer. Furthermore, this also facilitates offering the service at a lower cost by reducing the amount of human labor. Herein, the prime objective of this review is to provide a deep analysis encompassing the existing AI algorithms that are being deployed in the field of prostate cancer (PC) for diagnosis and treatment. Based on the available literature, AI-powered technology has the potential for extensive growth and penetration in PC diagnosis and treatment to ease and expedite the existing medical process.

Beneficial effects of adding magnesium to desalinated drinking water on metabolic and insulin resistance parameters among patients with type 2 diabetes mellitus: a randomized controlled clinical trial.

There is evidence that increasing the consumption of water containing magnesium can improve glucose metabolism and insulin resistance in patients with type 2 diabetes mellitus (T2DM). This trial was undertaken with the objective of evaluating the effect of adding different concentrations of magnesium chloride to the desalinated drinking water on the glycemic, metabolic, and insulin resistance parameters among patients with T2DM. A randomized cross-sectional controlled clinical trial was conducted to evaluate the effects of adding magnesium chloride supplement to desalinated drinking water consumed by patients with T2DM on the glycemic and metabolic parameters and indicators of insulin sensitivity. The total number of patients with T2DM who successfully completed the trial is 102. Patients were randomly allocated into three groups: the first group received bottled water without added magnesium (0 mg/L) (Group A, n = 37); the second group received bottled water with a low level of magnesium (20 mg/L) (Group B, n = 33); and the third group received drinking water with a high level of magnesium (50 mg/L) (Group C, n = 32). The daily consumption of elemental magnesium for a period of 3 months resulted in significant improvement in HbA1C (8.0 vs 8.2%, p = 0.04), insulin level (7.5 vs 9.9 µIU/mL, p = 0.03), and homeostasis model assessment-estimated insulin resistance (HOMA.IR) (2.5 vs 2.9, p = 0.002) in group C. However, there was no significant improvement in fasting blood glucose (FBS) level or lipid profile. The results of this study suggest that oral magnesium supplementation at the given dose of 50 mg/L daily added to drinking water could improve long-term glycemic control indicators and reduce insulin resistance in patients with T2DM.

Updates on Epstein-Barr Virus (EBV)-Associated Nasopharyngeal Carcinoma: Emphasis on the Latent Gene Products of EBV.

Nasopharyngeal carcinoma (NPC) is an uncommon type of malignancy/cancer worldwide. However, NPC is an endemic disease in southeast Asia and southern China and the reasons behind the underlying for such changes are unclear. Even though the Epstein-Barr infection (EBV) has been suggested as an important reason for undistinguishable NPC, the EBV itself is not adequate to source this type of cancer. The risk factors, for example, genetic susceptibility, and environmental factors might be associated with EBV to undertake a part in the NPC carcinogenesis. Normal healthy people have a memory B cell pool where the EBV persists, and any disturbance of this connection leads to virus-associated B cell malignancies. Less is known about the relationship between EBV and epithelial cell tumors, especially the EBV-associated nasopharyngeal carcinoma (EBVaNPC) and EBV-associated gastric carcinoma (EBVaGC). Currently, it is believed that premalignant genetic changes in epithelial cells contribute to the aberrant establishment of viral latency in these tumors. The early and late phases of NPC patients' survival rates vary significantly. The presence of EBV in all tumor cells presents prospects for the development of innovative therapeutic and diagnostic techniques, despite the fact that the virus's exact involvement in the carcinogenic process is presently not very well known. EBV research continues to shed light on the carcinogenic process, which is important for a more comprehensive knowledge of tumor etiology and the development of targeted cancer therapeutics. In order to screen for NPC, EBV-related biomarkers have been widely used in a few high-incidence locations because of their close associations with the risks of NPC. The current review highlights the scientific importance of EBV and its possible association with NPC.

Epstein-Barr virus infection mediated TP53 and Bcl-2 expression in nasopharyngeal carcinoma pathogenesis.

Epstein Barr virus (EBV) stimulates neoplastic transformation of nasopharyngeal epithelial cells through various molecular mechanisms, predominantly affecting inactivation of tumor-suppressor genes and activation of oncogenes. EBV infection is a major risk factor for nasopharyngeal carcinoma (NPC), yet its role in the carcinogenesis is not clear. EBV infection alters the expression of antiapoptotic proteins and tumor suppressor proteins. Therefore, this study investigated the correlation between EBV infection status with B cell lymphoma-2 (Bcl-2) and TP53 protein expression amongst laryngeal and nasopharyngeal cancer cases. This study was performed using 22 nasopharyngeal and 11 laryngeal cancer cases. EBV infection status, TP53 and Bcl-2 protein expression was studied using immunohistochemistry. The majority of the laryngeal cancer cases exhibited a poor prognosis and presented low Bcl-2 expression. A total of 22.7% cases were infected with EBV in the NPC cases. Upregulated TP53 expression was associated with EBV infection in the NPC cohort, and EBV infection was correlated with TP53 upregulation in the patients with NPC, suggesting mutual regulation between TP53 and EBV.

Polymorphic Variants in 5'-UTR Regions of the RAD51 Gene are Associated With RAD51 Expression and Triple-Negative Breast Cancer (TNBC): A Case-Control Study.

Breast cancer is a heterogeneous disease at morphologic and molecular levels, which is considered the most commonly occurring cancer in women. RAD51, a DNA-repairing protein, involves homologous recombination and has a vital role in genome stability. Polymorphism of the RAD51 gene, and its overexpression, has been proposed to be associated with the development of breast cancer. Overexpression of RAD51 in many types of human cancer including metastatic breast cancer may signify its potential use as a biomarker. Considering the numerous reports on the role of the 5'-UTR-RAD51 polymorphism in breast cancer, this study aimed to investigate the utility of RAD51 gene expression and its variants G135C and G172T as a possible foretelling factor of breast cancer development. DNA sequencing and immunohistochemistry of RAD51 were conducted on 103 samples from patients diagnosed with sporadic breast cancer and 80 samples from a control group. The results demonstrated that the RAD51 variants, G135C and G172T, were significantly presented in the breast cancer tissue compared with the control group. RAD51 expression was mainly shown in the cytoplasm of malignant cells (56% of cases) and significantly correlated with p53 and G135C, C135C variants. Moreover, the occurrence of the G172T variant was significantly associated with the expression of estrogen receptor. Interestingly, 21/26 (81%) of the triple-negative breast cancer showed G135C and C135C genotypes that were significantly associated with the expression of RAD51 (73%). In conclusion, the G135C and C135C variants together with the cytoplasmic expression of RAD51 may have clinical potential as a prognostic predictor for breast cancer development and aggressiveness.

Pathway-Affecting Single Nucleotide Polymorphisms (SNPs) in RPS6KA1 and MBIP Genes are Associated with Breast Cancer Risk.

BACKGROUND: Genetic mutations and polymorphisms play an important role in the transformation of primary cells to malignant cells as it may lead to disturbance of vital pathways regulating cell cycle, DNA damage repair, and apoptosis. In this study, we genotyped single nucleotide polymorphisms (SNPs) which were predicted to affect certain pathways and to increase the risk of breast cancer. METHODS: The study included 81 Saudi breast cancer patients and 100 matching healthy controls from the Eastern Province in Saudi Arabia. The following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) were then genotyped by TaqMan genotyping assay and the allele and genotype distribution was compared. RESULTS: The minor allele frequency of the following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) was T=0.17, A=0.28, A=0.22, and G=0.16 respectively. The G allele of the SNP rs3168891 was significantly associated with increased breast cancer risk (P = 0.00001) while the T allele of the same locus was associated with reduced risk of breast cancer in both heterozygous and homozygous states. The T allele of SNP rs2229714 which is located in the RPS6KA1 gene was also significantly associated with the increased risk of breast cancer. However, the rs2899849 SNP located in the Integrin beta-1 (ITGB1) gene was not associated with the increased risk of breast cancer in our study population. Haplotype analysis revealed the presence of three risk haplotypes that increases the risk of breast cancer (TGGT, TGTA, GATA). CONCLUSION: We showed that three, previously untested, SNPs are associated with increased risk of breast cancer in our population.  This may be added to the list of factors involved in breast cancer risk assessment studies. The benefit and the utility of the in-silico prediction of disease risk factors and their genetic association had been demonstrated in this study, yet the predicted risk alleles have to be tested in clinical studies.
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Is it mycosis fungoides? A comprehensive guide to reaching the diagnosis and avoiding common pitfalls.

Mycosis Fungoides (MF) is known as 'the great mimicker' due to its capacity to emulate several dermatoses, both in the clinic and on histology. This often leads to the diagnosis being missed or delayed, which consequently leads to poorer prognosis. For a timely diagnosis, it is crucial that the physician is aware of the various clinical and histological presentations of MF, as well as the proper diagnostic protocols. In the current review, we concisely encapsulate all the variants of MF as well has the conditions it mimics clinically and histologically. Through this, we aim to provide clinicians with a holistic picture of MF and help them determine when to suspect this disease and steps to take in order to nail the diagnosis.

Gliosarcoma case report and review of the literature.

Gliosarcoma is an unusual subtype of glioblastoma multiforme. Its characteristic features are biphasic configuration, constituting a definite, separate glial and sarcomatous differentiation, on histological evaluation. Herein, we present a rare case of Gliosarcoma that had presented only once in our center in last 13 years. A 60 years old, diabetic, hypertensive male patient came to e emergency department with disturbed level of consciousness and right sided hemiplegia which was progressive over four days. On examination he was, conscious, unoriented in time, person or place, his mouth deviated to left and vitally stable. After initial evaluation, CT scan and MRI were advised. These showed a complex left parieto-occipital heterogeneous mass lesion with cystic and solid components, measuring approximately 5.2x4cm. The mass lesion was seen displacing the occipital horn anteriorly and inferiorly with probable extension into the lateral ventricular cavity. There was no associated midline shift or definite herniation. The lesion was diagnosed as highly suggestive of brain tumor with a differential diagnosis of glioblastoma multiforme or ependymoma. Blood picture revealed a rapidly increasing level of anemia. Surgical intervention comprising left parieto-occipital craniotomy and near total resection of the tumor was carried out. On histopathological and immunohistochemical evaluation the diagnosis of GS was established. A plan of a combination of adjuvant chemotherapy and radiation was formulated that was however, declined by the family. On regular follow up, the patients clinical state rapidly deteriorated with persistence of seizures and requirement of repeated blood transfusions. The patient finally passed away after eighth months.

Helical and kinase domain mutations of PIK3CA, and their association with hormone receptor expression in breast cancer.

Breast cancer is one of the major causes of female morbidity and mortality, accounting for ~25% of the total cancer cases in women. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α subunit (PIK3CA) mutations serve a major role in downstream signaling of receptor tyrosine kinases. The present study aimed to elucidate the frequency of exon 9 and 20 mutations of PIK3CA and their role in disease progression. A total of 118 tumor samples from confirmed breast cancer patients were collected from the histopathology laboratory at King Fahd Hospital of the University (Al-Khobar, Saudi Arabia). Sanger sequencing was performed on extracted DNA to identify the mutations on exons 9 and 20 of PIK3CA. The results were further validated by competitive allele-specific TaqMan polymerase chain reaction. Three mutations, namely E542K and E545K within exon 9, and H1047R within exon 20, were observed in 25 patients (21.2%). Among these, 18 patients carried the H1047R mutation of the kinase domain, while the remaining 7 patients carried mutations in the helical domain. PIK3CA mutations were associated with the estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) group of tumors in contrast to the ER-/PR- group (P=0.021). Furthermore, it was observed that the PIK3CA mutation was associated with a poor disease prognosis. Taken together, the current study emphasized the potential of PIK3CA mutations as an important biomarker for breast cancer classification and the possible use of PIK3CA inhibitor as targeted therapy for breast cancer.

Chronic neurodegeneration by aflatoxin B1 depends on alterations of brain enzyme activity and immunoexpression of astrocyte in male rats.

Aflatoxin B1 poses the greatest risk among the mycotoxins to target-organisms particularly human, however, no studies addressed the neurotoxicity of chronic exposure of aflatoxin. The oral dose level 1/600th of LD50 for 30, 60, and 90 days was used for three aflatoxin groups, respective to negative and vehicle control groups. Activity levels of brain antioxidants viz: superoxide dismutase, catalase, glutathione, and glutathione peroxidase significantly decreased in the three experimental durations in time-dependent trend, in contrast, lipid peroxidation showed a significant increase compared to controls. Significantly, chronic-dependent increase trend was noticed in the AF60 and AF90 group for acid phosphatase (16.1%, 35.2%), alkaline phosphatase (32.1%, 50.8%), aspartate aminotransferase (38.7%, 120.0%) and lactate dehydrogenase (30.6%, 42.1%) activities, respectively. However, a significant 23.7% decrease in the brain creatine kinase activity following 90 days of AFB1administration. Chronic administration of aflatoxin also causes alterations in activities of protein carbonyl with a maximum increase (twofold) after 90 days. Further, histopathological and immunohistochemical results confirmed time-related vasodilation, necrosis and astrocytes gliosis by high glial fibrillary acidic protein immunostaining in response to AFB1. These findings infer that long-term exposure to AFB1 results in several pathophysiological circumstances in a duration-dependent manner concerning neurodegeneration especially Alzheimer's disease.

Gastrointestinal stromal tumors. A clinicopathological study.

OBJECTIVES: To evaluate the clinical presentations and immunohistochemical (IHC) properties of gastrointestinal stromal tumors (GISTs) and to compare them to internationally published data. METHODS: Thirty-six patients diagnosed with GISTs between January 1997 and December 2015 were retrospectively studied in 2 tertiary hospitals. Immunohistochemical staining was carried out prospectively when it has not been completed fully at the beginning. Results: The median age of patients was 54 years  (range; 17-81 years). Predominantly, we found more females were affected. The male to female ratio was 1:1.7. The most frequently affected organs were the stomach (63.8%) followed by small bowel (25%) and colorectal region (8.4%). Abdominal pain was the most frequent presentation in 33.3% of the patients then gastrointestinal (GI) bleeding in 30.5%. Most of the gastric GISTs were at early stages at presentation: stage 1 and II (60.8%), while in non-gastric GISTs, the tumor stage was advanced: stage III and IV (69.3%). The IHC characteristic of GIST in descending order showed positivity for vimentin (88.9%), CD117 (83.3%), CD34 (77.8%), Ki67 (63.9%), SMA (38.9%), desmin (27.8%), and S100 (19.4%). CONCLUSION: Gastrointestinal stromal tumors in our study demonstrates a major similar feature as the published international data. However, minor differences do exist in terms of clinical features and immunohistochemistry.

Alternative splicing is an important mechanism behind KAI1 loss of function in breast cancer patients from Saudi Arabia.

PURPOSE: KAI1 (also called CD82) is a metastasis suppressor gene known to be downregulated in breast cancer and other solid tumors. The downregulation of KAI1 or loss of its function is usually associated with bad prognosis. The mechanism behind KAI1 loss of function is complex. In this study, we investigated "alternative splicing" as a possible mechanism that underlies KAI1 loss of function in breast cancer patients from a tertiary hospital in Saudi Arabia. METHODS: Expression of KAI1 was studied in FFPE breast cancer and control tissue sections by IHC using two different antibodies targeting different domains of the protein. The TS82B antibody targets the extracellular loop, which constitutes most of the protein, while the second EPR4112 antibody targets the C-terminal intracellular domain of the protein. RESULTS: Out of 90 breast cancer samples, 67% showed loss of KAI1 expression. The remaining 33% showed KAI1 expression with (TS82B) antibody; however, the protein was detected in only 11% of cancers when using the antibody (EPR4112) indicating a truncation of the protein at the C-terminus (truncated-KAI1) in 22% of the studied cancer samples. A significant correlation was found between truncated-KAI1 expression and advanced cancer stage (association with lymph node metastasis, P value 0.008). CONCLUSION: Alternative splicing is an important mechanism underlying KAI1 loss of function in breast cancer, and it is associated with bad prognosis (advanced cancer stage).

In-vivo assessment of the osteo-protective effects of eugenol in alveolar bone tissues.

Estrogen deficiency following menopausal provokes alveolar bone loss, remodeling and inflammation. Eugenol is a phenolic compound with wide dental applications and anti-inflammatory properties. In the present study, the potential protective role of eugenol against alveolar bone deformities was investigated in an ovariectomized (OVX) rodent model. Two doses of eugenol (2.5 and 5 mg/kg/d) were administered to OVX animals for 12 weeks. In Serum, markers of bone metabolism and pro-inflammatory cytokines were estimated using ELISA. Alveolar bone morphometry was analyzed using high-resolution micro-computed tomography (CT). Bone histological analysis (H&E stain) was also performed. Alveolar bone expression of osteoclastogenesis modulating factors, such as osteoprotegerin (OPG), receptor activator of nuclear factor kappa-b ligand (RANKL) and inflammatory mediators, were measured using immunohistochemistry. Eugenol failed to correct elevated body weights and uterine atrophy in OVX rats. The significant elevation of bone metabolic markers and inflammatory cytokines in OVX animals were markedly improved by eugenol treatment, particularly the higher dose. Eugenol treatment considerably attenuated morphometric trabecular alterations of the alveolar bone and improved alveolar resorption and gingival infiltration. Alveolar bone of OVX animals showed augmented expression of RANKL, OPG and inflammatory cytokines, which were corrected by eugenol treatment. Alveolar bone loss and remodeling associated with estrogen insufficiency was ameliorated by eugenol owing to its anti-inflammatory properties, suggesting an extra dental impact for eugenol.