Biocompatibility profile of aged pigmented and non-pigmented silicone elastomer for combined maxillofacial defects.

PURPOSE: To assess the biocompatibility of platinum silicone elastomer A-2000 used in combined maxillofacial defects prosthesis, after being deteriorated by an accelerated aging process resembling both the extra and intraoral environment. This assessment was done indirectly on human-derived dermal and gingival tissues. MATERIALS AND METHODS: One hundred eight samples of room-temperature vulcanized A-2000 platinum silicone were equally divided into extrinsically pigmented and non-pigmented groups to replicate combined maxillofacial defects. Accelerated aging was applied to pigmented samples to mimic extra- and intra-oral conditions, while non-aged counterparts served as controls. After isolating human cell lineages, dermal and gingival fibroblasts were indirectly exposed to silicone sample media. Cytotoxicity to cultured fibroblasts was assessed via MTT assay. Statistical significance was determined by repeated measures of one-way ANOVA (p < 0.01), evaluating cytotoxicity on dermal and gingival fibroblasts. RESULTS: MTT assay showed increased cytotoxicity in pigmented silicon samples subjected to extraoral aging compared to non-aged counterparts (p < 0.01). Non-pigmented silicon, modeling intraoral conditions, exhibited cytotoxicity after 48 h (p < 0.05). Both aged and non-aged silicon extracts equally sensitized gingival fibroblasts at 72 h (p < 0.001). Negative correlations between pigmented and non-pigmented silicon were observed in dermal cell growth (p > 0.05, except at 24 h, r = 0.2), with accelerated aging showing minimal impact on the pigmentation effect (p > 0.05). CONCLUSION: The retrieved diminished cellular metabolic activity of platinum silicone elastomer was in an acceptable clinical range, pointing out the importance of periodic assessments of the maxillofacial prosthesis for replacement depending on aging and cytotoxic harmful cellular responses.

Antihypertensive Property of Celery: A Narrative Review on Current Knowledge.

Background: The incidence of hypertension is increasing significantly on a global scale, and it is considered the leading cause of heart disease and death. Despite the availability of hypotensive drugs, they have many side effects that decrease adherence to treatments and lead to uncontrolled blood pressure. Studies have revealed that celery contains bioactive compounds that oppose hypotensive effect. Methods: A thorough literature review was conducted using Scopus, PubMed, and Google Scholar databases. To identify relevant studies on the topic, our search strategy employed keywords such as "celery," "Apium gravenols L," "hypertension," "high blood pressure," "apigenin," "antihypertensive," and "hypotensive." The search was limited to articles published between January 2013 and December 2023. The inclusion criteria were original research articles that involved both animal and human subjects, published in English, and reported results applicable to the subject of this review. Review articles or articles in the form of theses or books were excluded. Results: The available evidence revealed that celery enhances blood pressure parameters. Clinical trials clarified that celery possesses its effect through many bioactive compounds, specifically 3-n-butylphthalide and apigenin. Based on animal and human studies, celery seems to elicit blood pressure regulation mainly by the vasodilatory, diuretic, and calcium channel-blocking properties. Furthermore, celery seed extract seems to exert a bradycardia effect. Conclusion: The current literature review showed a considerable number of studies on the hypertensive models, which confirmed that celery and its extracts are effective hypotensive agents. Some limitations in comparing published data should be considered, including differences in doses, extracts, species of celery, and administration form.

Aloe vera gel relieves cadmium triggered hepatic injury via antioxidative, anti-inflammatory, and anti-apoptotic routes.

Aloe vera (AV) gel extracted from fresh AV leaves was chosen in this study to evaluate its antioxidant, anti-inflammatory, and antiapoptotic activities against cadmium (Cd) -induced liver injury. Forty Wistar male adult rats were equally divided into four groups. Group I (standard control) ingested with 2.5 ml/kg b.w. of physiological saline. Group II (Cd-intoxicated) received 3 mg/kg b.w./day of CdCl2 dissolved in saline. Group III (AV) received 200 mg/kg b.w./day of AV gel dissolved in saline. Group IV (Cd+AV) ingested with 200 mg/kg b.w./day of AV gel solution along with 3 mg/kg b.w. CdCl2. All groups were ingested orally by gavage for 3 consecutive weeks. Paraoxonase-1 (PON-1) and HSP70 were measured in serum. The deposited Cd level, nitric oxide content, lipid peroxidation, collagen-1 (COL-1), and metalloproteinase-9 (MMP-9) levels were all determined in liver tissue homogenates. Gene expression of NF-κB and IL-6, Bax, and Bcl2, as well as immunohistochemistry analysis of activated caspase-3, was performed. Results showed that ingestion of AV gel greatly relieved all oxidative stress due to Cd exposure, modulated the NF-κB, IL-6, Bax, and Bcl2 expression levels, and improved the apoptotic state. In conclusion, AV gel confirmed its potential ameliorating effect against liver injury induced due to Cd exposure.

Awareness and Perception Toward Alzheimer's Disease Among Residents Living in the Jazan Province, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Alzheimer's disease (AD) is a growing public health concern, yet misconceptions about the condition are common. This study assessed awareness and social perceptions of AD in Jazan. METHODS: A cross-sectional survey of 925 adults was conducted. Knowledge was assessed using a 30-item Alzheimer's Disease Knowledge Scale (ADKS). Social perceptions were evaluated using a 10-item questionnaire. RESULTS: Many had misconceptions about AD epidemiology, causes, management, and care. The mean ADKS score was 8.89 ± 5.17 out of 30. Knowledge was poorest for symptoms, risk factors, treatment, caregiving, and life impact. Knowledge was highest in those aged >45 years (p = 0.018), in those with income > 15K SR (p = 0.004), in retired individuals (p = 0.023), and in those who learned about AD from books (p = 0.001), healthcare professionals (p = 0.001), or had an affected relative (p = 0.001). However, knowledge was low across all domains, averaging only 29% correct answers. Most respondents held positive social perceptions, yet sizable minorities saw isolation, legal intervention, and institutionalization as appropriate. Additionally, a portion of respondents associated stigma with individuals affected by AD and expressed a sense of burden associated with the condition. CONCLUSIONS: There are substantial knowledge gaps and some stigmatizing attitudes about AD in Jazan. Awareness regarding the causes, diagnosis, and management of AD was low. Misconceptions exist that AD only affects older people. Improved public education, especially for higher-risk groups, is needed to address misconceptions and promote social inclusion for those with dementia. Healthcare professionals can play a crucial role.

Testicular Infarction in a Sickle Cell Hemoglobinopathy Patient: A Case Report.

Vaso-occlusive phenomena in sickle cell disease lead to ischemia and possible infarction of the affected organ. We report a case of a 20-year-old Saudi male known to have homozygous sickle cell hemoglobinopathy who was admitted to our institution with abdominal pain. One day post admission, the patient developed left testicular pain. Ultrasound showed decreased echogenicity, and Doppler examination showed absent blood flow in the left testicle. Left radical orchidectomy was done, and histopathological assessment revealed ischemic necrosis with sickled red blood cells (RBCs). A few studies have been reported worldwide suggesting that a vaso-occlusive event is the mainstay mechanism in such cases. This is the first case reported in the Eastern Province of Saudi Arabia.

Transfusion-Associated Graft-Versus-Host Disease in Adults.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but fatal complication of blood transfusion that usually develops two to 30 days following a blood transfusion giving rise to graft versus host disease (GVHD) clinical features that are consisting of fever, skin rash, jaundice, diarrhea, and pancytopenia. The disease is fulminant in most patients with a mortality rate of >90% of cases. The main aim of this review is to enhance awareness among medical practitioners about this fatal disease. Data were extracted manually from the main medical databases (Medline, Scopus, and Google Scholar) after the revision of selected articles and assessed for their contribution to the knowledge of TA-GVHD. TA-GVHD occurs when the viable donor T-cells in the blood or blood products attack the recipient's tissues which his/her immune system is incapable to destroy due to several reasons. The recipient's tissues that are usually involved in TA-GVHD include the liver, intestine, skin, lungs, and bone marrow. Any blood component either whole blood, packed red blood cells (RBCs), platelets, or fresh non-frozen plasma that contains viable T lymphocytes can cause TA-GVHD. Host immunodeficiency, transfusion of fresh blood, and partial human leukocyte antigen (HLA) matching between the donors and the recipients represent the major risk factors of TA-GVHD. Partial HLA matching includes immunocompetent recipients who receive blood from a first-degree relative also, seen in genetically homogenous populations because of high rates of consanguineous marriage. The diagnosis of TA-GVHD is mainly suspected based on clinical manifestations. However, a histopathological study of either skin or rectal biopsy is diagnostic. The treatment of TA-GVHD is generally not effective, unless the patient received emergency stem cell transplantation, while prevention via irradiation of blood or blood products represents the standard of care for this disease. In conclusion, medical practitioners should have a high index of suspicion for this disease. Moreover, future clinical trials targeting and comparing the outcomes of the different therapeutic options for TA-GVHD are required.

Oxygen Saturation in Hospitalized COVID-19 Patients and Its Relation to Colchicine Treatment: A Retrospective Cohort Study with an Updated Systematic Review.

Background: Colchicine has been proposed as a cytokine storm-blocking agent for COVID-19 due to its efficacy as an anti-inflammatory drug. The findings of the studies were contentious on the role of colchicine in preventing deterioration in COVID-19 patients. We aimed to evaluate the efficacy of colchicine in COVID-19-hospitalized patients. Design: A retrospective observational cohort study was carried out at three major isolation hospitals in Alexandria (Egypt), covering multiple centers. In addition, a systematic review was conducted by searching six different databases for published studies on the utilization of colchicine in patients with COVID-19 until March 2023. The primary outcome measure was to determine whether colchicine could decrease the number of days that the patient needed supplemental oxygen. The secondary outcomes were to evaluate whether colchicine could reduce the number of hospitalization days and mortality rate in these patients. Results: Out of 515 hospitalized COVID-19 patients, 411 were included in the survival analysis. After adjusting for the patients' characteristics, patients not receiving colchicine had a shorter length of stay (median: 7.0 vs. 6.0 days) and fewer days of supplemental oxygen treatment (median: 6.0 vs. 5.0 days), p < 0.05, but there was no significant difference in mortality rate. In a subgroup analysis based on oxygen equipment at admission, patients admitted on nasal cannula/face masks who did not receive colchicine had a shorter duration on oxygen supply than those who did [Hazard Ratio (HR) = 0.76 (CI 0.59-0.97)]. Using cox-regression analysis, clarithromycin compared to azithromycin in colchicine-treated patients was associated with a higher risk of longer duration on oxygen supply [HR = 1.77 (CI 1.04-2.99)]. Furthermore, we summarized 36 published colchicine studies, including 114,878 COVID-19 patients. Conclusions: COVID-19-hospitalized patients who were given colchicine had poorer outcomes in terms of the duration of supplemental oxygen use and the length of their hospital stay. Therefore, based on these findings, the use of colchicine is not recommended for COVID-19-hospitalized adults.

Seaweed Sargassum aquifolium extract ameliorates cardiotoxicity induced by doxorubicin in rats.

Doxorubicin (DOX) is a potent anticancer drug with adverse cardiotoxic effects. Alginates are multifunctional biopolymers and polyelectrolytes derived from the cell walls of brown seaweeds. They are nontoxic, biocompatible, and biodegradable, and hence, utilized in several biomedical and pharmaceutical applications. Here, we investigated the potential cardioprotective effect of thermally treated sodium alginate (TTSA), which was extracted and purified from the seaweed Sargassum aquifolium, in treating acute DOX cardiotoxicity and apoptotic pathways in rats. UV-visible spectroscopy, Fourier-transform infrared, and nuclear magnetic resonance (1H-NMR) spectroscopy techniques were used to characterize TTSA. CK-MB and AST levels in sera samples were determined. The expression levels of Erk-2 (MAPK-1) and iNOS genes were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of Erk-2, anti-apoptotic p53, and caspase-3 were analyzed using western blotting and ELISA. For the in vivo studies, sixty rats were randomly divided equally into six groups and treated with DOX, followed by TTSA. We revealed that treatment with TTSA, which has low molecular weight and enhanced antioxidant properties, improved DOX-mediated cardiac dysfunction and alleviated DOX-induced myocardial apoptosis. Furthermore, TTSA exhibited a cardioprotective effect against DOX-induced cardiac toxicity, indicated by the increased expression of MAPK-1 (Erk2) and iNOS genes, which are implicated in the adaptive responses regulating DOX-induced myocardial damage. Moreover, TTSA significantly (p < 0.05) suppressed caspase-3 and upregulated anti-apoptotic protein p53 expression. TTSA also rebalanced the cardiomyocyte redox potential by significantly (p < 0.05) increasing the levels of endogenous antioxidant enzymes, including catalase and superoxide dismutase. Our findings suggest that TTSA, particularly at a dose of 400 mg/kg b.w., is a potential prophylactic supplement for treating acute DOX-linked cardiotoxicity.

Association between CNR1 gene polymorphisms and susceptibility to diabetic nephropathy in Iraqi patients with T2DM.

In individuals with type 2 diabetes mellitus (T2DM), the cannabinoid receptor 1 (CNR1) gene polymorphism has been linked to diabetic nephropathy (DN). Different renal disorders, including DN, have been found to alter cannabinoid (CB) receptor expression and activation. This cross-sectional study aimed to investigate the relationship between CNR1 rs1776966256 and rs1243008337 genetic variants and the risk of developing DN in Iraqi patients with T2DM. The study included 100 patients with T2DM, divided into two groups: 50 with DN and 50 without DN. Genotyping of CNR1 rs1776966256 and rs1243008337 polymorphisms was conducted using PCR in DN patients and control samples. The distribution of rs1776966256 and rs1243008337 genotypes and alleles between the two groups revealed statistically significant differences. The frequencies of the GG and AG genotypes of CNR1 rs1776966256 were significantly different between DN patients and the control group. Additionally, compared to the A allele, the G allele of this polymorphism was linked to a higher incidence of DN (p=0.0001). Patients with the genetic polymorphism rs1243008337 had higher genotypes of CC and AC and were more likely to develop DN in the polymorphism genotype than the wild genotype. Additionally, compared to the A allele, the C allele was linked to a higher chance of developing DN (p=0.0001). Both rs1776966256 and rs1243008337 polymorphisms were correlated with the development of diabetic nephropathy.

In Silico and In Vivo Evaluation of microRNA-181c-5p's Role in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a fatal disease, accounting for 75-85% of primary liver cancers. The conclusive research on miR-181c-5p's role in hepatocarcinogenesis, whether it has oncogenic effects or acts as a tumor repressor, is limited and fluctuating. Therefore, the current study aimed to elucidate the role of miR-181c-5p in HCC in silico and in vivo. The bioinformatics analysis of miR-181c-5p expression data in HCC using several databases strongly shed light on its involvement in HCC development, but also confirmed the fluctuating data around its role. miR-181c-5p was proven here to have an oncogenic role by increasing HepG2 cells' viability as confirmed by MTT analysis. In addition, miR-181c-5p was upregulated in the HCC positive control group and progressed the HCC development and malignant features by its forced expression in an HCC mouse model by targeted delivery using a LA-PAMAM polyplex. This is indicated by the cancerous gross and histological features, and the significant increase in liver function biomarkers. The functional enrichment bioinformatics analyses of miR-181c-5p-downregulated targets in HCC indicated that miR-181c-5p targets were significantly enriched in multiple pathways and biological processes involved in HCC development. Fbxl3, an example for miR-181c-5p potential targets, downregulation and its correlation with miR-181c-5p were validated by qPCR. In conclusion, miR-181c-5p is upregulated in HCC and has an oncogenic role enhancing HCC progression.

Unilateral cataract and congenital stationary night blindness in a child with novel variants in TRPM1.

Unilateral cataract can cause pediatric vision impairment. Although the majority of unilateral cataracts are idiopathic in nature, genetic causes have been reported. We present the case of a 4-week-old child of nonconsanguineous parents who was affected with unilateral cataract. Whole-genome sequencing using DNA extracted from blood and the lens epithelial cells following cataract surgery revealed two presumed pathogenic variants in the TRPM1 gene, the founding member of the melanoma-related transient receptor potential (TRPM) subfamily. TRPM1 is responsible for regulating cation influx to hyperpolarized retinal ON bipolar cells, and mutations in this gene are a major cause of autosomal recessive congenital stationary night blindness (CSNB). Electroretinography revealed findings consistent with CSNB, a phenotype that was not initially suspected, and which would likely have been missed without genome sequencing. It remains unclear whether the TRPM1 variants are associated with the cataract phenotype.

Angiofibroma of the Mandible: Report of a Rare Case.

Angiofibroma is an uncommon, highly vascular benign lesion that occurs in the head and neck region, typically arising in the nasopharyngeal area, potentially with a locally aggressive course. Angiofibroma with a primary intraoral presentation is extremely rare; few case reports have been published in the literature, with only three cases of angiofibroma in the mandible published to date. In this case, a 37-year-old man presented with swelling at the right mandible and underwent enucleation of the lesion under general anesthesia. After 1-year follow-up, there were no signs of recurrence.

Neuroprotective effect of sodium alginate against chromium-induced brain damage in rats.

Oral exposure to chromium hexavalent [Cr(VI)] has disastrous impacts and affects many people worldwide. Cr(VI) triggers neurotoxicity via its high oxidation potential by generating high amount of ROS. Meanwhile, alginates are known by their chelating activity and ability to bind heavy metals and toxins, in addition to their antioxidant, anti-inflammatory, and anti-apoptotic activities. So, this study aimed to explore the neuroprotective potential of sodium alginate (SA) against cellular injury, DNA damage, macromolecule alterations, and apoptosis induced by oral ingestion of Cr. Forty Wistar male rats were divided into 4 groups; group I: standard control ingested with the vehicle solution, group II: Cr-intoxicated group received 10 mg/kg b.w. of potassium dichromate orally by gavage and kept without treatment, group III: SA group in which rats were orally exposed to 200 mg/kg b.w. of SA only, and group IV: SA-treated group that received 200 mg/kg b.w. of SA along with Cr for 28 consecutive days. Neurotransmitters such as Acetyl choline esterase (AchE), Monoamine oxidase A (MAOA) concentrations, Dopamine (DA) and 5-Hydroxytryptamine (5-HT) levels were assessed in brain homogenate tissues. Neurobiochemical markers; NAD+ and S100B protein were investigated in the brain tissues and serum, respectively. Levels of HSP70, caspase-3, protein profiling were evaluated. DNA damage was determined using the Comet assay. Results revealed a significant reduction in the AchE and MAOA concentrations, DA, 5-HT, and NAD+ levels, with an increase in the S100B protein levels. Cr(VI) altered protein pattern and caused DNA damage. High levels of HSP70 and caspase-3 proteins were observed. Fortunately, oral administration of SA prevented the accumulation of Cr in brain homogenates and significantly improved all investigated parameters. SA attenuated the ROS production and relieved the oxidative stress by its active constituents. SA can protect against cellular and DNA damage and limit apoptosis. SA could be a promising neuroprotective agent against Cr(VI)-inducing toxicity.

High seroprevalence of SARS-CoV-2 among high-density communities in Saudi Arabia.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection had been investigated utilizing serology. MATERIALS AND METHODS: This community-based sero-survey was carried out in the neighborhoods of three cities in Saudi Arabia. RESULTS: Of 5629 participants, 2766 (49.1%) were women; and 2148 (38.1%) were 18-34 years of age, and 3645 (64.7%) were from South East Asia. Positive serology was seen in 2825 (50.2% (95% CI: 48.8-51.5%) for SARS-CoV-2 anti-S1 IgG antibodies by ECLIA. Being in the age category of 18-34 years and being from Eastern Mediterranean Region (country A) were associated with higher COVID-19 seropositivity with estimated odds ratio of 1.3 [95% CI 1.1-1.8] and 2.5 [95% CI 1.1.5-4.2] respectively. Gender, social status, education, nationality, symptoms, presence of comorbidities and activity style were positively associated with increased seropositivity. Factors associated negatively with the rate of seropositivity were higher education and having outdoor activity with estimated OR of 0.92 [95% CI 0.46-0.95] and 0.59 [95% CI 0.47-0.74], respectively. CONCLUSION: The study showed high seroprevalence of SARS-CoV-2 among high density population. Health education campaigns should target middle-aged, those with low education, those living in lower standards and indoor workers.

Comparative Natural History of Visual Function From Patients With Biallelic Variants in BBS1 and BBS10.

Purpose: The purpose of this study was to compare the natural history of visual function change in cohorts of patients affected with retinal degeneration due to biallelic variants in Bardet-Biedl syndrome genes: BBS1 and BBS10. Methods: Patients were recruited from nine academic centers from six countries (Belgium, Canada, France, New Zealand, Switzerland, and the United States). Inclusion criteria were: (1) female or male patients with a clinical diagnosis of retinal dystrophy, (2) biallelic disease-causing variants in BBS1 or BBS10, and (3) measures of visual function for at least one visit. Retrospective data collected included genotypes, age, onset of symptoms, and best corrected visual acuity (VA). When possible, data on refractive error, fundus images and autofluorescence (FAF), optical coherence tomography (OCT), Goldmann kinetic perimetry (VF), electroretinography (ERG), and the systemic phenotype were collected. Results: Sixty-seven individuals had variants in BBS1 (n = 38; 20 female patients and 18 male patients); or BBS10 (n = 29; 14 female patients and 15 male patients). Missense variants were the most common type of variants for patients with BBS1, whereas frameshift variants were most common for BBS10. When ERGs were recordable, rod-cone dystrophy (RCD) was observed in 82% (23/28) of patients with BBS1 and 73% (8/11) of patients with BBS10; cone-rod dystrophy (CORD) was seen in 18% of patients with BBS1 only, and cone dystrophy (COD) was only seen in 3 patients with BBS10 (27%). ERGs were nondetectable earlier in patients with BBS10 than in patients with BBS1. Similarly, VA and VF declined more rapidly in patients with BBS10 compared to patients with BBS1. Conclusions: Retinal degeneration appears earlier and is more severe in BBS10 cases as compared to those with BBS1 variants. The course of change of visual function appears to relate to genetic subtypes of BBS.

Expression of HCV genotype-4 core antigen in prokaryotic E. coli system for diagnosis of HCV infection in Egypt.

BACKGROUND: Egypt has a high prevalence of hepatitis C virus (HCV) infection with 92.5% of genotype-4. AIM: This study aimed to clone and express the core gene of HCV genotype-4 for using it to develop a highly sensitive, specific, and cost-effective diagnostic assay for detecting HCV infection. METHODS: Using synthetic HCV genotype-4 core gene, pET15b as E. coli expression vector, and 1 mM lactose as inducer, the HCV core protein (MW 17 kDa) was expressed in the form of inclusion bodies (IBs) that was purified and solubilized using 8 M guanidinium HCl. The recombinant core protein was in vitro refolded by a rapid dilution method for further purification using weak cation exchange liquid chromatography. The immunogenicity of the purified protein was tested by ELISA using 129 serum samples. RESULTS: The recombinant core protein was successfully expressed and purified. The results also showed that the in-house anti-HCV core assay is accurate, specific (~96.6%), and highly sensitive (~100%) in accordance with the commercial ELISA kit. CONCLUSION: The sensitivity, specificity, and reproducibility of the developed assay were high and promising to be used as a screening assay for detecting HCV infection.

Genotype-phenotype correlation of 33 patients with maple syrup urine disease.

Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder due to defects in the branched-chain α-ketoacid dehydrogenase complex (BCKDC). MSUD varies in severity and its clinical spectrum is quite broad, ranging from mild to severe phenotypes. Thirty-three MSUD patients were recruited into this study for molecular genetic variant profiling and genotype-phenotype correlation. Except for one patient, all other patients presented with the classic neonatal form of the disease. Seventeen different variants were detected where nine were novel. The detected variants spanned across the entire BCKDHA, BCKDHB and DBT genes. All variants were in homozygous forms. The commonest alterations were nonsense and frameshift variants, followed by missense variants. For the prediction of variant's pathogenicity, we used molecular modeling and several in silico tools including SIFT, Polyphen2, Condel, and Provean. In addition, six other tools were used for the prediction of the conservation of the variants' sites including Eigen-PC, GERP++, SiPhy, PhastCons vertebrates and primates, and PhyloP100 rank scores. Herein, we presented a comprehensive characterization of a large cohort of patients with MSUD. The clinical severity of the variants' phenotypes was well correlated with the genotypes. The study underscores the importance of the use of in silico analysis of MSUD genotypes for the prediction of the clinical outcomes in patients with MSUD.

Genome-wide gene expression analysis of a murine model of prostate cancer progression: Deciphering the roles of IL-6 and p38 MAPK as potential therapeutic targets.

BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among adult males globally. The poor prognosis of PCa is largely due to late diagnosis of the disease when it has already progressed to an advanced stage marked by androgen-independence, thus necessitating new strategies for early detection and treatment. We construe that these direly needed advances are limited by our poor understanding of early events in the progression of PCa and that would thus represent ideal targets for early intervention. To begin to fill this void, we interrogated molecular "oncophenotypes" that embody the transition of PCa from an androgen-dependent (AD) to-independent (AI) state. METHODS: To accomplish this aim, we used our previously established AD and AI murine PCa cell lines, PLum-AD and PLum-AI, respectively, which recapitulate primary and progressive PCa morphologically and molecularly. We statistically surveyed global gene expressions in these cell lines by microarray analysis. Differential profiles were functionally interrogated by pathways, gene set enrichment and topological gene network analyses. RESULTS: Gene expression analysis of PLum-AD and PLum-AI transcriptomes (n = 3 each), revealed 723 differentially expressed genes (392 upregulated and 331 downregulated) in PLum-AI compared to PLum-AD cells. Gene set analysis demonstrated enrichment of biological functions and pathways in PLum-AI cells that are central to tumor aggressiveness including cell migration and invasion facilitated by epithelial-to-mesenchymal transition (EMT). Further analysis demonstrated that the p38 mitogen-activated protein kinase (MAPK) was predicted to be significantly activated in the PLum-AI cells, whereas gene sets previously associated with favorable response to the p38 inhibitor SB203580 were attenuated (i.e., inversely enriched) in the PLum-AI cells, suggesting that these aggressive cells may be therapeutically vulnerable to p38 inhibition. Gene set and gene-network analysis also alluded to activation of other signaling networks particularly those associated with enhanced EMT, inflammation and immune function/response including, but not limited to Tnf, IL-6, Mmp 2, Ctgf, and Ptges. Accordingly, we chose SB203580 and IL-6 to validate their effect on PLum-AD and PLum-AI. Some of the common genes identified in the gene-network analysis were validated at the molecular and functional level. Additionally, the vulnerability to SB203580 and the effect of IL-6 were also validated on the stem/progenitor cell population using the sphere formation assay. CONCLUSIONS: In summary, our study highlights pathways associated with an augmented malignant phenotype in AI cells and presents new high-potential targets to constrain the aggressive malignancy seen in the castration-resistant PCa.

CYR61/CCN1 expression in resected pancreatic ductal adenocarcinoma: A retrospective pilot study of the interaction between the tumors and their surrounding microenvironment.

BACKGROUND: CCN1 is an extracellular matrix-associated protein thought to be implicated in tumor-stromal interaction in several solid tumors. The aim of our pilot study was to evaluate the correlation between CCN1 expression in stromal cells, pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma cells in resected pancreatic ductal adenocarcinoma (PDAC) specimens, and correlate that clinically. METHODS: A total of 42 paraffin-embedded PDAC tumor specimens were stained for CCN1 and evaluated via immunohistochemical (IHC) analysis. Statistical analysis was performed to correlate between CCN1 expression profiles in tumor tissues and clinicopathological parameters of patients. RESULTS: Our results showed CCN1 (CYR61) gene was highly expressed in PDAC tissues relative to other organ specific tumor tissues. Also, moderate and overexpression of CCN1 in PanIN was associated with PanIN grade 3 tissues. A statistically significant association was found between PanIN CCN1 scores on one hand and cancer stage, cancer grade, and CCN1 expression among ductal tumor cells and adjacent stromal cells on the other hand. DISCUSSION: The associations demonstrated suggest that CCN1 might be contributing to a substantial role in the interaction between the pancreatic tumors on one hand and their surrounding microenvironment and their precursors on the other hand; hence, it might serve as a potential therapeutic target for PDAC.

The efficacy of Coenzyme Q10 and liquid paraffin oil in the management of acute aluminum phosphide poisoning.

Aluminum phosphide (AlP) poisoning had high morbidities and mortalities with absence of a standardized approach for the treatment. The present study investigated the efficiency of GIT decontamination methods and Coenzyme Q10(Co Q10) (Ubiquinone) in improving the outcome of acute AlP poisoning. A total of 90 patients were included and all patients received immediately supportive measures, then they distributed into three equal groups: In group I, gastric lavage was done using KMNO4 solution (1:10 000); group II received 250-500 ml liquid paraffin oil orally; group III received 300 mg of Co Q10 dissolved in liquid paraffin. Co Q10 was continued in a dose of 200 mg/day every 12 h. Follow-up blood pressure, arterial blood gases, serum troponin level and need for intubation revealed that the best improvement was in group III followed by group II. The percentage of survivors was 76.67% in group III and 70% of the patients had no residual effects. In group II, the survivors were 63.33%, and 36.67% of the cases discharged without sequelae. The survivors in group I constituted 26.67% and only 16.67% of the patients had no residual effects. GIT decontamination with aqueous solutions in acute AlP poisoning should be avoided. Rapid oral intake of any available oil as a prehospital treatment or immediately on hospital admission could critically improve the outcome of acute AlP poisoning. Besides, the addition of Co Q10 to the oil further improve patients' prognosis. HighlightsAcute aluminum phosphide (AlP) poisoning is associated with high mortalities.The appropriate method of GIT decontamination in acute AlP poisoning is controversy.Conventional gastric lavage was associated with poor prognosis in acute AlP poisoning.GIT decontamination using liquid paraffin oil improved outcome of acute AlP poisoning.Coenzyme Q10 ameliorated AlP toxicity with improvement of cardiac functions.