Association of specific ACE2 and TMPRSS2 variants with circulatory cytokines of COVID-19 Emirati patients.

Introduction: The COVID-19 pandemic represented one of the most significant challenges to researchers and healthcare providers. Several factors determine the disease severity, whereas none alone can explain the tremendous variability. The Single nucleotide variants (SNVs) in angiotensin-converting enzyme-2 (ACE2) and transmembrane serine protease type-2 (TMPRSS2) genes affect the virus entry and are considered possible risk factors for COVID-19. Methods: We compiled a panel of gene variants from both genes and used in-silico analysis to predict their significance. We performed biological validation to assess their capacity to alter the ACE2 interaction with the virus spike protein. Subsequently, we conducted a retrospective comparative genome analysis on those variants in the Emirati patients with different disease severity (total of 96) along with 69 healthy control subjects. Results: Our results showed that the Emirati population lacks the variants that were previously reported as associated with disease severity, whereas a new variant in ACE2 "Chr X:g.15584534" was associated with disease severity specifically among female patients. In-silico analysis revealed that the new variant can determine the ACE2 gene transcription. Several cytokines (GM-CSF and IL-6) and chemokines (MCP-1/CCL2, IL-8/CXCL8, and IP-10/CXCL10) were markedly increased in COVID-19 patients with a significant correlation with disease severity. The newly reported genetic variant of ACE2 showed a positive correlation with CD40L, IL-1ß, IL-2, IL-15, and IL-17A in COVID-19 patients. Conclusion: Whereas COVID-19 represents now a past pandemic, our study underscores the importance of genetic factors specific to a population, which can influence both the susceptibility to viral infections and the level of severity; subsequently expected required preparedness in different areas of the world.

Biocompatibility of 3D-Printed Dental Resins: A Systematic Review.

BACKGROUND: The biocompatibility of 3D-printed dental resins has become a critical concern in modern dentistry due to the increasing utilization of additive manufacturing (AM) techniques in dental applications. These resins serve as essential materials for fabricating dental prostheses, orthodontic devices, and various dental components. As the clinical adoption of 3D printing in dentistry grows, it is imperative to comprehensively assess the biocompatibility of these materials to ensure patient safety and dental treatment efficacy. This systematic review aimed to evaluate the existing body of literature on the biocompatibility of 3D-printed dental resins, thereby providing valuable insights into the potential biological risks associated with their use. METHODS: The search strategy to identify relevant papers was implemented across PubMed/MEDLINE, Scopus, Web of Science, Embase, Cochrane Library, CINAHL, and Google Scholar to identify relevant studies. Study selection was not limited to any particular timeframe of publishing. The revised CONSORT criteria were used to ascertain the authenticity and dependability of the review's outcomes. Comprehensive screening and eligibility assessment processes were conducted to select studies meeting predefined criteria. Biocompatibility-related parameters, including toxicity, mechanical properties, cell viability, and other relevant outcomes, were analyzed across selected studies using a standardized variable extraction protocol. RESULTS: A total of 9 studies were included in the systematic review. The findings encompassed various aspects of biocompatibility assessment, including material composition, mechanical properties, cell viability, and cytotoxicity. Some studies revealed significant improvements in flexural strength and cell viability with specific resin formulations, demonstrating their potential for enhanced clinical utility. Conversely, certain resins exhibited cytotoxicity, while others displayed promising biocompatibility profiles. CONCLUSION: As per the assessed findings, material composition, post-processing techniques, and manufacturing methods emerged as critical factors influencing biocompatibility outcomes. While some resins exhibited favorable biocompatibility profiles, others raised concerns due to cytotoxicity. These findings emphasize the need for careful consideration when selecting and implementing 3D-printed dental resins, with a focus on materials engineering and comprehensive biocompatibility testing. Further research is warranted to elucidate the long-term biocompatibility and clinical implications of these materials.

University Pre-Professional Program: A Transitional Phase from Didactic to PBL Pedagogy.

Purpose: The College of Science and Health Professions offers the University Pre-Professional Program (UPPP) to newly enrolled students. This study aimed to evaluate the effectiveness of the program in preparing students to become self-directed learners and to seek students' perceptions about student-centered teaching. Methods: A quantitative quasi-experimental study that used a pre and post-test survey in two stages, before and after semester-4. A self-developed questionnaire was distributed online. Results: The t-test showed students (n=701) after semester-4 had a significant increase in the understanding of Problem-Based Learning (PBL) (t (699) = -8.27, p < 0.01), PBL dynamics (t (699) = -5.12, p < 0.01), learning and dynamics of Case-Based Learning (CBL) and Self-Directed Learning (SDL) (t (699) = -6.48, p < 0.01), and facilitators' role in such curriculum (t (699) = -3.41, p < 0.01). The ANOVA showed students attending various courses perceived the program variables differently (Learning in PBL p = 0.08, PBL dynamics p < 0.01, CBL and SDL dynamics p < 0.01, role of facilitator in PBL p < 0.01). Regarding the resources used by students during the basic medical sciences courses, no significant difference was observed between the study groups (p = 0.06). However, the only significant difference observed was in their satisfaction with the question related to assessment and course (p < 0.01). Conclusion: The UPPP improved students' understanding of student-centered teaching and learning approaches, especially the PBL. Thus, UPPP helps students shift their learning habits from didactic to student-centered modern learning approaches. Variation among different students' groups could be attributed to their previous academic background and change in learning medium to English. This study suggests that preparatory teaching programs like UPPP are helpful for students interested in joining the bachelor's programs in countries like Saudi Arabia where English is not a native language.

Globoid Cell Leukodystrophy (Krabbe Disease): An Update.

Globoid cell leukodystrophy or Krabbe is a disease that affects children as well as adults who have mutations in the gene encoding the enzyme galactosylceramidase/galctocerebrosidase (GALC), resulting in the deposition of the toxic lipid D-galactosyl-beta1-1' sphingosine (GalSph or psychosine). Several therapeutic modalities were used to treat patients with Krabbe disease, including hematopoietic stem cell transplantation, enzyme replacement therapy, autophagy activators, intravenous immunoglobulin, and inhibitors of the Pyroptosis process, among many other approaches. In this article, I will briefly discuss the disease in both human and animal model, describe recent clinical observations as well as methods utilizing genetic analysis for diagnosis, and finally review recent advances in treating this rare and devastating disease.

Awareness of Epidural Analgesia Among Childbearing Women in Western Region of Saudi Arabia: A Cross-Sectional Study.

Background Labor pain is one of the most excruciating experiences that women can go through. Epidural anesthesia (EDA) is the most prevalent form of labor analgesia considered as a secure and effective method of pain relief for women during active labor. The EDA works by numbing the nerves that cause pain. To our knowledge, only a few studies have been conducted on the use of EDA in Saudi Arabia. Objectives The purpose of this study was to assess the awareness of EDA among childbearing women in the western region of Saudi Arabia. Methods We carried out a cross-sectional study using a self-administered online questionnaire to measure awareness about EDA. The study targeted the general population of women from the western region of Saudi Arabia who were aged between 18 and 50 years. A total of 1,137 questionnaires were returned and analyzed. Results This study assessed the perspectives of 1,137 women. The results revealed that 52.6% of women who received EDA showed a good level of knowledge of the procedure, while 26.1% of women had not experienced EDA (P = 0.001). Good knowledge of EDA was detected among 39.3% of women aged 36-50 years. This rate was significantly higher than that of women younger than 20 years old, of which 24.3% had good knowledge (P = 0.038). Conclusion This study shows that women in this particular region have a lack of knowledge about EDA. Therefore, it is recommended that more education about EDA be provided during antenatal visits to improve awareness.

Solitary fibrous tumor of the orbit in a 1-year-old patient: a case report.

Solitary fibrous tumors (SFTs) are rare neoplasms of mesenchymal origin. While the mean age of presentation is 58 years old, we report the case of the youngest documented patient with an SFT of the orbit. A 13-month-old child was evaluated for eyelid asymmetry and then referred to the oculoplastic service. On examination, a soft tissue mass of the right inferomedial orbit was observed. MRI demonstrated a well-circumscribed, extraocular lesion in the inferomedial right orbit, potentially fibrous in nature. Excision was performed without complications. Pathologic examination demonstrated fibrous tissue proliferation with a staghorn vascular pattern, as well as benign fibrous cells with tapering nuclei and abundant pericellular reticulin. Immunohistochemistry (IHC) demonstrated that the cells stain diffusely positive for CD34 and vimentin. With the MRI findings, pathology, and IHC, the diagnosis was confirmed to be SFT. SFTs of the orbit, although rare, may occur in the pediatric population.

Titanium Particles Modulate Lymphocyte and Macrophage Polarization in Peri-Implant Gingival Tissues.

Titanium dental implants are one of the modalities to replace missing teeth. The release of titanium particles from the implant's surface may modulate the immune cells, resulting in implant failure. However, little is known about the immune microenvironment that plays a role in peri-implant inflammation as a consequence of titanium particles. In this study, the peri-implant gingival tissues were collected from patients with failed implants, successful implants and no implants, and then a whole transcriptome analysis was performed. The gene set enrichment analysis confirmed that macrophage M1/M2 polarization and lymphocyte proliferation were differentially expressed between the study groups. The functional clustering and pathway analysis of the differentially expressed genes between the failed implants and successful implants versus no implants revealed that the immune response pathways were the most common in both comparisons, implying the critical role of infiltrating immune cells in the peri-implant tissues. The H&E and IHC staining confirmed the presence of titanium particles and immune cells in the tissue samples, with an increase in the infiltration of lymphocytes and macrophages in the failed implant samples. The in vitro validation showed a significant increase in the level of IL-1ß, IL-8 and IL-18 expression by macrophages. Our findings showed evidence that titanium particles modulate lymphocyte and macrophage polarization in peri-implant gingival tissues, which can help in the understanding of the imbalance in osteoblast-osteoclast activity and failure of dental implant osseointegration.

The Public's Knowledge of Osteoarthritis and Its Related Risk Factors in Makkah, Saudi Arabia.

Background Osteoarthritis (OA) is a chronic progressive disease that leads to the destruction of the articular cartilage inside the joint. OA is a common everyday musculoskeletal disorder worldwide, and it is believed that OA is triggered by genetics and environmental factors, including age, which is the most significant risk factor. This study aimed to investigate the general population's knowledge of OA and its related risk factors in Makkah, Saudi Arabia. Methodology This cross-sectional study was performed between December 2022 and January 2023 among the general population of Makkah, Saudi Arabia using an online survey using Google Forms. An appropriate statistical analysis was then conducted on the collected data. Results A total of 1,087 participants enrolled in this study. According to the multivariate logistic regression analysis, 48% (n = 789) of the participants reported that OA occurs due to joint cartilage age and use. In total, 69.7% of the participants knew that OA is a chronic problem, 84.4% knew it is a common disease, and 39.3% thought that all types of joints can suffer from OA. Over half (53.1%) of the participants knew that joint stiffness is a sign of OA, and 63.4% thought that OA may lead to the loss of joint motion. Over four-fifths (82.5%) thought that advancing age is a risk factor for OA, and 27.5% incorrectly thought that the incidence of OA is equal between men and women. Overall, 62.9% of the participants knew about clinical examinations and X-rays. Moreover, 78% thought that physiotherapy can improve the symptoms of OA, and 65.3% thought that some types of exercise can help. Finally, 35.8% of the participants had an overall awareness of OA, while 64.2% had poor awareness. Conclusions The general public of Makkah showed low knowledge of OA and its associated risk factors. Many misunderstandings about the causes, risk factors, and treatment of OA were acknowledged. Awareness campaigns with brochures and flyers can be used to raise the population's knowledge.

Liver Injury Associated with COVID-19 Infection: Pathogenesis, Histopathology, Prognosis, and Treatment.

Liver injury occurs frequently as a consequence of SARS-CoV-2 infection. Direct infection of the liver leads to hepatic impairment with elevated transaminases. In addition, severe COVID-19 is characterized by cytokine release syndrome, which may initiate or exacerbate liver injury. In patients with cirrhosis, SARS-CoV-2 infection is associated with acute-on-chronic liver failure. The Middle East and North Africa (MENA) region is one of the world's regions characterized by a high prevalence of chronic liver diseases. Both parenchymal and vascular types of injury contribute to liver failure in COVID-19, with a myriad of pro-inflammatory cytokines playing a major role in perpetuating liver injury. Additionally, hypoxia and coagulopathy complicate such a condition. This review discusses the risk factors, and the underlying causes of impaired liver functions in COVID-19, with a focus on key players in the pathogenesis of liver injury. It also highlights the histopathological changes encountered in postmortem liver tissues as well as potential predictors and prognostic factors of such injury, in addition to the management strategies to ameliorate liver damage.

Hyperlipidemia and Hypertension Are Associated With Intracerebral Hemorrhage Incidence: A Retrospective Study.

Introduction Stroke places a huge burden on the socioeconomic systems. Hemorrhagic stroke (HS) is the second most common type of stroke and the second leading cause of disability and death. The updated data on the prevalence of intracerebral hemorrhage (ICH) stroke and related physiological risk factors in Saudi Arabia were limited. The aim of this study was to identify the prevalence of ICH stroke and the related physiological risk factors. Methods This was a retrospective, hospital-based, and chart review study that utilized the BESTCare system at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Patients who attended the neurology department (inpatient/outpatient) between 2015 and 2020 were studied. The statistical tool JMP (JMP Inc., Cary, NC, USA) was used for data entry and analysis. Results Patient data (N = 1,870, 58.6 ± 13.87 years old) were screened for comorbidities, hypertension (66.1%), diabetes mellitus (DM) (57.7%), hyperlipidemia (28.4%), and history of an old stroke (22.3%). Ischemic stroke (IS) was more dominant than ICH stroke with ratios of 94.5% (n = 1767) versus 5.5% (n = 103), respectively. The prevalence of ICH stroke among the patients (n = 103) was 10.6%, 20.3%, 24.2%, and 28.1% in the age groups of <40, 41-50, 51-60, and 61-70 years old, respectively. There was a significant gender effect on the distribution of both IS and ICH (p = 0.003). ICH strokes were more prevalent in males than in females. Body mass index (BMI) has no significant effect on the prevalence of IS and ICH stroke (p = 0.081). ICH stroke was significantly associated with DM (p = 0.032), hypertension (p = 0.01), and hyperlipidemia (p = 0.002). Regression analyses show that only hypertension (positive association) and hyperlipidemia (negative association) were significantly associated with the incidence of ICH stroke. Conclusion IS was more prevalent than ICH stroke. ICH strokes were more prevalent in males than in females. Also, hypertension was the most common factor leading to ICH stroke, unlike hyperlipidemia, which was revealed to be protective against ICH stroke.

A Cross-Sectional Study of the Knowledge, Practice, and Attitude Towards Herpes Zoster Vaccination Among the General Population in the Western Region of Saudi Arabia.

Introduction Herpes zoster (HZ) is a viral infection that occurs due to the reactivation of the varicella-zoster virus. The vaccination against herpes zoster to prevent its complications has been approved for individuals 50 years of age and older. This study aims to evaluate the knowledge, attitudes, and habits of at-risk populations about the varicella-zoster virus and its vaccination. Methodology A quantitative, observational, cross-sectional study was conducted among 500 adults over 50 years of age. Participants were selected by non-probability, convenience sampling from public places. RStudio (R version 4.1.1) was used to analyze the data. Result Eighty-three percent (n = 416) of participants had heard of herpes zoster (HZ). Seventy-four percent of respondents (n = 368) did not recognize the link between varicella and herpes zoster. Multiple linear regression showed that individuals who had varicella and heard about herpes zoster were the only positive predictors of herpes zoster knowledge. Out of all the respondents, 55.8% (n = 279) had heard of the herpes zoster vaccine, but 94.6% (n = 473) had not taken it. Among the respondents, 28.1% (n = 118) were unwilling to take optional vaccines; 77.4% (n = 387) agreed to take the HZ vaccine if recommended by a healthcare professional. Conclusion The general Saudi population had a good understanding of HZ and its vaccine. Their attitudes toward the HZ vaccine were generally positive; however, poor practices were observed. We recommend that arranging national campaigns targeting at-risk populations can enhance awareness about herpes zoster and its vaccine, subsequently increasing the rate of HZ immunization.

Toll-like receptor 9 signaling after myocardial infarction: Role of p66ShcA adaptor protein.

During myocardial infarction, cellular debris is released, causing a sterile inflammation via pattern recognition receptors. These reactions amplify damage and promotes secondary heart failure. The pattern recognition receptor, Toll-like receptor 9 (TLR9) detects immunogenic fragments of endogenous DNA, inducing inflammation by NFκB. The p66ShcA adaptor protein plays an important role in both ischemic myocardial damage and immune responses. We hypothesized that p66ShcA adaptor protein promotes DNA-sensing signaling via the TLR9 pathway after myocardial infarction. TLR9 protein expression increased in cardiac tissue from patients with end-stage heart failure due to ischemic heart disease. Myocardial ischemia in mice in vivo induced gene expression of key TLR9 pathway proteins (MyD88 and Unc93b1). In this model, a functional link between TLR9 and p66ShcA was revealed as; (i) ischemia-induced upregulation of TLR9 protein was abrogated in myocardium of p66ShcA knockout mice; (ii) when p66ShcA was overexpressed in NFkB reporter cells stably expressing TLR9, NFkB-activation increased during stimulation with the TLR9 agonist CpG B; (iii) in cardiac fibroblasts, p66ShcA overexpression caused TLR9 upregulation. Co-immunoprecipitation showed that ShcA proteins and TLR9 may be found in the same protein complex, which was dissipated upon TLR9 stimulation in vivo. A proximity assay confirmed the co-localization of TLR9 and ShcA proteins. The systemic immune response after myocardial ischemia was dampened in p66ShcA knockout mice as interleukin-4, -17 and -22 expression in mononuclear cells isolated from spleens was reduced. In conclusion, p66ShcA adaptor may be an interaction partner and a regulator of the TLR9 pathway post-infarction.

CXCL10 Chemokine: A Critical Player in RNA and DNA Viral Infections.

Chemokines constitute a group of small, secreted proteins that regulate leukocyte migration and contribute to their activation. Chemokines are crucial inflammatory mediators that play a key role in managing viral infections, during which the profile of chemokine expression helps shape the immune response and regulate viral clearance, improving clinical outcome. In particular, the chemokine ligand CXCL10 and its receptor CXCR3 were explored in a plethora of RNA and DNA viral infections. In this review, we highlight the expression profile and role of the CXCL10/CXCR3 axis in the host defense against a variety of RNA and DNA viral infections. We also discuss the interactions among viruses and host cells that trigger CXCL10 expression, as well as the signaling cascades induced in CXCR3 positive cells.

Identification and Characterization of Plasmids and Genes from Carbapenemase-Producing Klebsiella pneumoniae in Makkah Province, Saudi Arabia.

Klebsiella pneumoniae (K. pneumoniae) is involved in several hospital and community-acquired infections. The prevalence of K. pneumoniae-producing-carbapenemase (KPC) resistance genes rapidly increases and threatens public health worldwide. This study aimed to assess the antibiotic resistance level of K. pneumoniae isolates from Makkah Province, Saudi Arabia, during the Islamic 'Umrah' ritual and to identify the plasmid types, presence of genes associated with carbapenem hydrolyzing enzymes, and virulence factors. The phenotypic and genotypic analyses based on the minimum inhibitory concentration (MIC), biofilm formation, PCR, and characterization of KPC-encoding plasmids based on the replicon typing technique (PBRT) were explored. The results showed that most isolates were resistant to carbapenem antibiotics and other antibiotics classes. This study identified sixteen different replicons of plasmids in the isolates and multiple genes encoding carbapenem factors, with blaVIM and blaOXA-48 being the most prevalent genes identified in the isolates. However, none of the isolates exhibited positivity for the KPC production activity. In addition, this study also identified six virulence-related genes, including kfu, wabG, uge, rmpA, fimH, and a capsular polysaccharide (CPS). Together, the data reported in this study indicate that the isolated K. pneumoniae during the pilgrimage in Makkah were all resistant to carbapenem antibiotics. Although the isolates lacked KPC production activity, they carried multiple carbapenem-resistant genes and virulence factors, which could drive their resistant phenotype. The need for specialized methods for KPC detection, monitoring the possibility of nosocomial transmission, and diverse therapeutic alternatives are necessary for controlling the spreading of KPC. This study can serve as a reference for clinicians and researchers on types of K. pneumoniae commonly found during religious gathering seasons in Saudi Arabia.

A flow electrochemistry-enabled synthesis of 2-substituted N-(methyl-d)piperidines.

A synthesis of N-monodeuteriomethyl-2-substituted piperidines is described. An efficient and readily scalable anodic methoxylation of N-formylpiperidine in an undivided microfluidic electrolysis cell delivers methoxylated piperidine 3, which is a precursor to a N-formyliminium ion and enables C-nucleophiles to be introduced at the 2-position. The isotopically labelled N-deuteriomethyl group is installed using the Eschweiler-Clarke reaction with formic acid-d2 and unlabelled formaldehyde. Monodeuterated N-methyl groups in these molecular systems possess small isotropic proton chemical shift differences important in the investigation of molecules that are able to support long-lived nuclear spin states in solution nuclear magnetic resonance.

Expression of immune checkpoints (PD-L1 and IDO) and tumour-infiltrating lymphocytes in breast cancer.

Background: Breast cancer (BC) has become the most common cancer globally in 2020 as well as in the United Arab Emirates. The breast tumor microenvironment is composed of various immune cell types, including lymphocytes. Tumour-infiltrating lymphocytes (TILs) play a crucial role in tumor eradication and progression. Further, immune checkpoint markers such as programmed death receptor ligand 1 (PD-L1) and indoleamine-2,3-dioxygenase (IDO) have been associated with tumor evasion from the immune system. In this study, we aimed to explore the status of TILs, PD-L1 and IDO as well as to investigate their association with the clinicopathological parameters. Materials and methods: A total of 59 patients diagnosed with primary infiltrating BC were selected, after which tissue sections were stained to identify TILs along with immunohistochemical staining of PD-L1 and IDO. Moreover, in-silico tools were used to assess the expression of PD-L1, IDO and CD3ε in various molecular subtypes of BC. Results: It was found that the percentage of TILs correlated with estrogen receptor (ER) and progesterone receptor (PR) expression. This was supported by the finding that most of the triple-negative breast cancer (TNBC) cases belonged to the group with a high percentage of TILs (h-TILs). Similarly, the expression of PD-L1 and IDO was correlated with the ER and PR, whereas TNBC cases showed a high expression of PD-L1 and IDO. This goes in line with the in-silico findings where the TNBC group showed the highest expression of PD-L1 and IDO as well as the T cell marker CD3ε. Conclusion: This study highlighted a possible link between the immunosuppressive markers PD-L1 and IDO with TILs density in the BC microenvironment.

Development and Validation of Reverse Transcriptase Loop-Mediated Isothermal Amplification (RT-LAMP) as a Simple and Rapid Diagnostic Tool for SARS-CoV-2 Detection.

Since the COVID-19 pandemic outbreak in the world, many countries have searched for quick diagnostic tools to detect the virus. There are many ways to design diagnostic assays; however, each may have its limitations. A quick, sensitive, specific, and simple approach is essential for highly rapidly transmitted infections, such as SARS-CoV-2. This study aimed to develop a rapid and cost-effective diagnostic tool using a one-step Reverse Transcriptase Loop-Mediated Isothermal Amplification (RT-LAMP) approach. The results were observed using the naked eye within 30-60 min using turbidity or colorimetric analysis. The sensitivity, specificity, and lowest limit of detection (LoD) for SARS-CoV-2 RNA against the RT-LAMP assay were assessed. This assay was also verified and validated against commercial quantitative RT-PCR used by health authorities in Saudi Arabia. Furthermore, a quick and direct sampling from the saliva, or buccal cavity, was applied after simple modification, using proteinase K and heating at 98 °C for 5 min to avoid routine RNA extraction. This rapid single-tube diagnostic tool detected COVID-19 with an accuracy rate of 95% for both genes (ORF1a and N) and an LoD for the ORF1a and N genes as 39 and 25 copies/reaction, respectively. It can be potentially used as a high-throughput national screening for different respiratory-based infections within the Middle East region, such as the MERS virus or major zoonotic pathogens such as Mycobacterium paratuberculosis and Brucella spp., particularly in remote and rural areas where lab equipment is limited.

Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance.

Colorectal cancer (CRC) is among the topmost malignancies for both genders. Despite the high incidence rate and advances in diagnostic tools, treatment in many cases is still ineffective. Most cancerous lesions in CRC begin as benign, followed by the development of invasive forms and metastases. The development of CRC has been linked to defects in autophagy, which plays both a pro-and anti-tumor role and is mainly context-dependent. Autophagy suppression could enhance apoptosis via p53 activation, or autophagy also promotes tumor progression by maintaining tumor growth and increasing resistance to chemotherapy. Autophagy promotes the invasion and metastasis of CRC cells via increased epithelial-mesenchymal transition (EMT). Moreover, dysbiosis of gut microbiota upregulated autophagy and metastasis markers. Autophagy responses may also modulate the tumor microenvironment (TME) via regulating the differentiation process of several innate immune cells. Treatments that promote tumor cell death by stimulating or inhibiting autophagy could be beneficial if used as an adjunct treatment, but the precise role of various autophagy-modulating drugs in CRC patients is needed to be explored. In this article, we present an overview of the autophagy process and its role in the pathogenesis and therapeutic resistance of CRC. Also, we focused on the current understanding of the role of the EMT and TME, including its relation to gut microbiota and immune cells, in autophagic manipulation of CRC. We believe that there is a potential link between autophagy, TME, EMT, and drug resistance, suggesting that further studies are needed to explore this aspect.

Cross section empirical formulation for (n, 2n) nuclear reactions on natural isotopes from Z= 21 to Z= 79 for neutron energy range, 8-20 MeV.

Neutron induced reactions with different target materials and isotopes are very important for completion of nuclear data base as well as for many applications. Since the experimental determinations of the reaction cross sections for such reactions are not always available, attempts were made to introduce empirical or semi empirical formulae. In this work, new empirical formulation for (n, 2n) nuclear reactions on natural isotopes for neutron energies range 8-20 MeV, based on some published experimental works. The deuced formulae are then used to calculate the excitation functions for the (n,2n) on target isotopes having atomic numbers in the range 21-79. The cross section values for many reactions, having previously measured values, are determined and inter-comparison with the experimental and the TENDL-2019 database values are given using some statistical error parameters. Special attention was made to some Lanthanide isotopes. The results showed satisfied predictions in most cases.

Identifying Immunological and Clinical Predictors of COVID-19 Severity and Sequelae by Mathematical Modeling.

Since its emergence as a pandemic in March 2020, coronavirus disease (COVID-19) outcome has been explored via several predictive models, using specific clinical or biochemical parameters. In the current study, we developed an integrative non-linear predictive model of COVID-19 outcome, using clinical, biochemical, immunological, and radiological data of patients with different disease severities. Initially, the immunological signature of the disease was investigated through transcriptomics analysis of nasopharyngeal swab samples of patients with different COVID-19 severity versus control subjects (exploratory cohort, n=61), identifying significant differential expression of several cytokines. Accordingly, 24 cytokines were validated using a multiplex assay in the serum of COVID-19 patients and control subjects (validation cohort, n=77). Predictors of severity were Interleukin (IL)-10, Programmed Death-Ligand-1 (PDL-1), Tumor necrosis factors-α, absolute neutrophil count, C-reactive protein, lactate dehydrogenase, blood urea nitrogen, and ferritin; with high predictive efficacy (AUC=0.93 and 0.98 using ROC analysis of the predictive capacity of cytokines and biochemical markers, respectively). Increased IL-6 and granzyme B were found to predict liver injury in COVID-19 patients, whereas interferon-gamma (IFN-γ), IL-1 receptor-a (IL-1Ra) and PD-L1 were predictors of remarkable radiological findings. The model revealed consistent elevation of IL-15 and IL-10 in severe cases. Combining basic biochemical and radiological investigations with a limited number of curated cytokines will likely attain accurate predictive value in COVID-19. The model-derived cytokines highlight critical pathways in the pathophysiology of the COVID-19 with insight towards potential therapeutic targets. Our modeling methodology can be implemented using new datasets to identify key players and predict outcomes in new variants of COVID-19.