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Clinical features, risk factors and a prediction model for in-hospital mortality among diabetic patients infected with COVID-19: data from a referral centre in Iran
No full textObjectives: The aim of this study was to identify risk factors of in-hospital mortality among diabetic patients infected with COVID-19. Study design: This is a retrospective cohort study. Methods: Using logistic regression analysis, the independent association of potential prognostic factors and COVID-19 in-hospital mortality was investigated in three models. Model 1 included demographic data and patient history; model 2 consisted of model 1, plus vital signs and pulse oximetry measurements at hospital admission; and model 3 included model 2, plus laboratory test results at hospital admission. The odds ratios (ORs) and 95 confidence intervals (95 CIs) were reported for each predictor in the different models. Moreover, to examine the discriminatory powers of the models, a corrected area under the receiver-operating characteristic curve (AUC) was calculated. Results: Among 560 patients with diabetes (men = 291) who were hospitalised for COVID-19, the mean age of the study population was 61.8 (standard deviation SD 13.4) years. During a median length of hospitalisation of 6 days, 165 deaths (men = 93) were recorded. In model 1, age and a history of cognitive impairment were associated with higher mortality; however, taking statins, oral antidiabetic drugs and beta-blockers was associated with a lower risk of mortality (AUC = 0.76). In model 2, adding the data for respiratory rate (OR 1.07 95% CI 1.00�1.14) and oxygen saturation (OR 0.95 95% CI 0.92�0.98) slightly increased the AUC to 0.80. In model 3, the data for platelet count (OR 0.99 95% CI 0.99�1.00), lactate dehydrogenase (OR 1.002 95% CI 1.001�1.003), potassium (OR 2.02 95% CI 1.33�3.08) and fasting plasma glucose (OR 1.04 95% CI 1.02�1.07) significantly improved the discriminatory power of the model to AUC 0.86 (95% CI 0.83�0.90). Conclusions: Among patients with type 2 diabetes, a combination of past medical and drug history and pulse oximetry data, with four non-expensive laboratory measures, was significantly associated with in-hospital COVID-19 mortality. © 2021 The Royal Society for Public Healt
Molecular docking evaluation of celecoxib on the boron nitride nanostructures for alleviation of cardiovascular risk and inflammatory
No full textCelecoxib (CXB) is a nonsteroidal anti-inflammatory drug (NSAID) that can be used to treat rheumatoid arthritis and ischemic heart disease. In this research, density functional theory (DFT) and molecular docking simulations were performed to study the interaction of boron nitride nanotube (BNNT) and boron nitride nanosheet (BNNS) with CXB and its inhibitor effect on pro-inflammatory cytokines. The calculated adsorption energies of CXB with the BNNT were determined in aqueous phase. The results revealed that adsorption of CXB molecule via its SO2 group on BNNT is thermodynamically favored than the NH2 and CF3 groups in the solvent environment. Adsorption of CXB on BN nanomaterials are weak physisorption in nature. This can be attributed to the fact that both phenyl groups in CXB are not on the same plane and require significant activation energies for conformational changes to obtain greater H-� interaction. Both BNNT and BNNS materials had huge sensitivity in electronic change and short recovery time during CXB interaction, thus having potential as molecular sensor and biomedical carrier for the delivery of CXB drug. IL-1A and TNF-α were implicated as vital cytokines in diverse diseases, and they have been a validated therapeutic target to manage cardiovascular risk in patients with inflammatory bowel disease. A molecular docking simulation confirms that the BNNT loaded CXB could inhibit more pro-inflammatory cytokines including IL-1A and TNF-α receptors as compared to BNNS loaded to CXB. © 2021 The Author(s
Development of a high-performance PVA/DOPA bone adhesive incorporated with bioactive glass and hydroxyapatite particles for highly comminuted bone fractures
No full textBone adhesives, a new promising sort of clinical treatment for bone fractures, despite all the advantages, are concerned with cytotoxicity, mechanical strength, and fixation in the wet body environment. A procedure using Polyvinyl Alcohol and an excellent adhesion agent, Dihydroxyphenylalanine incorporated with hydroxyapatite and bioactive glass particles designed to meet a bone adhesive�s requirements. Improved wet adhesion strength, 20.5 MPa tensile strength for highly comminuted bone fractures, 99.97 cell viability alongside resistance against both gram-negative and gram-positive bacteria, and controllable biodegradation indicated that the synthesized bone adhesive is of great potential for highly comminuted bone fractures. © 2021 Taylor & Francis
SOX2OT lncRNA Inhibition Suppresses the Stemness Characteristics of Esophageal Tumorspheres
No full textBackground: SOX2OT is a novel cancer associated long non-coding RNA (LncRNA) with higher expression in variable tumor tissues, including esophageal squamous cell carcinoma (ESCC). It also plays an important function in embryonic neuronal development. Regarding its function in both stemness and carcinogenesis, here, we aimed to investigate its expression and function in tumorspheres of the esophagus using the RNAi method. Material & Methods: Two esophageal squamous cancer cells (ESCC): KYSE30 and YM1 cells were used for sphere enrichment. Cells were transfected with SOX2OT targeting and control siRNA. The size and the number of spheres were measured using light microscopy. Gene expression of the pluripotency genes was measured by qRT-PCR and docetaxel chemoresistance was assessed by MTS viability assay. Results: Our findings showed that ESCC tumorspheres overexpress SOX2OT gene along with other stemness genes (SOX2, OCT4A, and Nanog) compared to their original cancer cells. RNAi experiments indicated that SOX2OT knockdown can suppress the stemness-related gene expression, sphere formation ability (both size and number), and docetaxel resistance as three of the main cancer stem cell characteristics of tumorspheres. Conclusion: Altogether our results showed the regulatory role of SOX2OT in pluripotency and stemness in ESCC tumorspheres. Our results suggest a potential application of SOX2OT inhibition in combination with docetaxel for ESCC inhibition in vitro. © 2022 by the authors
Quantitative analysis of Merkel cell polyomavirus (MCPyV) genome in non-melanoma skin cancer and normal tumor margins
No full textMerkel cell polyomavirus (MCPyV) is the cause of approximately 80 of Merkel cell carcinomas (MCC). The common types of non-melanoma skin cancer (NMSC) including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are histologically similar to MCC. In the present study, 58 NMSC formalin-fixed paraffin-embedded tissue (FFPE) samples including 12 SCC, 46 BCC, and 58 FFPE samples of adjacent non-tumoral margins as the control were included. Determination of large tumor antigens (LTAg) copy number was performed by qReal-Time PCR as a viral copy number per cell to elucidate MCPyV carcinogenic role in non-melanoma skin cancer. Out of 58 samples, 36 (62) cancerous and 22 (37.9) normal tumor margins were positive for MCPyV LTAg. Median copy numbers of MCPyV LTAg among all NMSC samples and non-tumoral margins were 0.308�10�2 and 0.269�10�3 copies per cell respectively (P=0.001). In addition, although the viral load in the majority of samples was detected to be lower than one copy per cell, in 4 BCC samples, a viral load higher than one LTAg copy per cell was detected. The present study revealed that the detection of higher levels of MCPyV LTAg viral load in some BCC and SCC samples may be correlated with the role of MCPyV in some cases of BCC and SCC skin cancer. © 2022, The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia
Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy
No full textBackground: Gastric cancer imposes a substantial global health burden despite its overall incidence decrease. A broad spectrum of inherited, environmental and infectious factors contributes to the development of gastric cancer. A profound understanding of the molecular underpinnings of gastric cancer has lagged compared to several other tumors with similar incidence and morbidity rates, owing to our limited knowledge of the role of carcinogens in this malignancy. The International Agency for Research on Cancer (IARC) has classified gastric carcinogenic agents into four groups based on scientific evidence from human and experimental animal studies. This review aims to explore the potential comprehensive molecular and biological impacts of carcinogens on gastric cancer development and their interactions and interferences with various cellular signaling pathways. Conclusions: In this review, we highlight recent clinical trial data reported in the literature dealing with different ways to target various carcinogens in gastric cancer. Moreover, we touch upon other multidisciplinary therapeutic approaches such as surgery, adjuvant and neoadjuvant chemotherapy. Rational clinical trials focusing on identifying suitable patient populations are imperative to the success of single-agent therapeutics. Novel insights regarding signaling pathways that regulate gastric cancer can potentially improve treatment responses to targeted therapy alone or in combination with other/conventional treatments. Preventive strategies such as control of H. pylori infection through eradication or immunization as well as dietary habit and lifestyle changes may reduce the incidence of this multifactorial disease, especially in high prevalence areas. Further in-depth understanding of the molecular mechanisms involved in the role of carcinogenic agents in gastric cancer development may offer valuable information and update state-of-the-art resources for physicians and researchers to explore novel ways to combat this disease, from bench to bedside. Graphical abstract: A schematic outlining of the interaction between gastric carcinogenic agents and intracellular pathways in gastric cancer H. pylori stimulates multiple intracellular pathways, including PI3K/AKT, NF-κB, Wnt, Shh, Ras/Raf, c-MET, and JAK/STAT, leading to epithelial cell proliferation and differentiation, apoptosis, survival, motility, and inflammatory cytokine release. EBV can stimulate intracellular pathways such as the PI3K/Akt, RAS/RAF, JAK/STAT, Notch, TGF-β, and NF-κB, leading to cell survival and motility, proliferation, invasion, metastasis, and the transcription of anti-apoptotic genes and pro-inflammatory cytokines. Nicotine and alcohol can lead to angiogenesis, metastasis, survival, proliferation, pro-inflammatory, migration, and chemotactic by stimulating various intracellular signaling pathways such as PI3K/AKT, NF-κB, Ras/Raf, ROS, and JAK/STAT. Processed meat contains numerous carcinogenic compounds that affect multiple intracellular pathways such as sGC/cGMP, p38 MAPK, ERK, and PI3K/AKT, leading to anti-apoptosis, angiogenesis, metastasis, inflammatory responses, proliferation, and invasion. Lead compounds may interact with multiple signaling pathways such as PI3K/AKT, NF-κB, Ras/Raf, DNA methylation-dependent, and epigenetic-dependent, leading to tumorigenesis, carcinogenesis, malignancy, angiogenesis, DNA hypermethylation, cell survival, and cell proliferation. Stimulating signaling pathways such as PI3K/Akt, RAS/RAF, JAK/STAT, WNT, TGF-β, EGF, FGFR2, and E-cadherin through UV ionizing radiation leads to cell survival, proliferation, and immortalization in gastric cancer. The consequence of PI3K/AKT, NF-κB, Ras/Raf, ROS, JAK/STAT, and WNT signaling stimulation by the carcinogenic component of Pickled vegetables and salted fish is the Warburg effect, tumorigenesis, angiogenesis, proliferation, inflammatory response, and migration. Figure not available: see fulltext. © 2022, Springer Nature Switzerland AG
L-carnitine: Searching for New Therapeutic Strategy for Sepsis Management
No full textIn this review, we discussed the biological targets of carnitine, its effects on immune function, and how L-carnitine supplementation may help critically ill patients. L-carnitine is a potent antioxidant. L-carnitine depletion has been observed in prolonged intensive care unit (ICU) stays, while L-carnitine supplementation has beneficial effects in health promotion and regulation of immunity. It is essential for the uptake of fatty acids into mitochondria. By inhibiting the ubiquitin-proteasome system, down-regulating the apelin receptor in cardiac tissue, and reducing β-oxidation of fatty acid, carnitine may decrease vasopressor requirement in septic shock and improve clinical outcomes of this group of patients. We also reviewed animal and clinical studies that have been recruited for evaluating the beneficial effects of L-carnitine in the management of sepsis/ septic shock. Additional clinical data are required to evaluate the optimal daily dose and dura-tion of L-carnitine supplementation. © 2022 Bentham Science Publishers
Exacerbation of Congenital Hydronephrosis as the First Presentation of COVID-19 Infection in Children
No full textBackground. Congenital hydronephrosis is one of the most common abnormalities of the upper urinary tract, which can be exacerbated by a variety of intrinsic or extrinsic triggers. The urinary tract system is one of the major organs complicated by COVID-19 infection. Case Presentations. Here, we report five patients with an established diagnosis of congenital hydronephrosis, who presented with acute abdominal pain and fever and an abrupt increase in the anteroposterior pelvic diameter (APD). Patients had a previous stable course and were under regular follow-up with serial ultrasonographic studies. They underwent surgery or supportive treatment due to the later exacerbation of hydronephrosis. Based on the clinical and imaging findings, no plausible etiologies for these exacerbation episodes, including infection, nephrolithiasis, or abdominal masses, could be postulated. The common aspect in all these patients was the evidence of a COVID-19 infection. Conclusions. Infection with COVID-19 in children with antenatal hydronephrosis may exacerbate the degree of hydronephrosis and renal APD in ultrasonography, which itself may be mediated by the increase in inflammatory mediators. © 2022 Masoumeh Mohkam et al
Oncolytic virus delivery modulated immune responses toward cancer therapy: Challenges and perspectives
No full textOncolytic viruses (OVs) harness the hallmarks of tumor cells and cancer-related immune responses for the lysis of malignant cells, modulation of the tumor microenvironment, and exertion of vaccine-like activities. However, efficient clinical exploitation of these potent therapeutic modules requires their systematic administration, especially against metastatic and solid tumors. Therefore, developing methods for shielding a virus from the neutralizing environment of the bloodstream while departing toward tumor sites is a must. This paper reports the latest advancements in the employment of chemical and biological compounds aimed at safe and efficient delivery of OVs to target tissues or tumor deposits within the host. © 2022 Elsevier B.V
Unusual Presentation of Pulmonary Interstitial Glycogenosis: A Case Report Study
No full textIntroduction: Pulmonary interstitial glycogenosis (PIG) is a kind of children�s interstitial lung disease (ChILD). This is exclusively limited to neonates and infants. Often, PIG is diagnosed in the lung biopsy in a short time after birth (usually < 6 months). Most cases of PIG in infants are symptomatic within the first days to weeks of life. PIG expresses itself with diverse clinical symptoms such as tachypnea and hypoxia and may lead to acute respiratory failure in neonates. Case Presentation: In this case report study, we presented a 1.5-year-old boy with the chief complaint of stage 4 clubbing in fingers and toes. Mild chest deformity was observed in his physical exam. No evidence of respiratory and cardiac complications was observed. Initial lab tests and further specific studies were normal. His parents did not mention the history of any diseases in this patient. His chest X-ray (CXR) showed hyperinflated lungs, diffuse bilateral interstitial infiltration, and hazy opacities. Ground glass opacities (GGO) and interlobular septal thickening and cystic changes with reversed halo sign in both lungs were observed in his chest computerized tomography (CT). Finally, pulmonary biopsy showed a high level of glycogen-laden mesenchymal cells in the interstitium of alveoli, and vimentin-positive interstitial infiltration in lung parenchyma confirmed the PIG diagnosis. Conclusions: The new manifestation of PIG, which has been reported in this case, can be beneficial for future diagnoses of PIG. Copyright © 2021, Author(s)