Revealing New Prospects: Antipsychotic Drugs Exert Anti-Tumor Effects against Gastric Cancer through Inducing Apoptosis.

BACKGROUND AND OBJECTIVE: Globally, Gastric Cancer (GC) ranks as the fifth leading cause of cancer-related deaths. GC is a multifaceted malignancy with diverse etiologies; however, understanding the shared molecular mechanisms can aid in discovering novel targeted therapies for GC. This study has employed a drug repositioning approach to explore new drug candidates for treating GC. METHODS: The human GC cell lines AGS, MKN-45, and KATO-III were treated with different concentrations of dopamine, cabergoline, thioridazine, and entacapone to determine effective doses and IC50 values. In vitro, cytotoxic activity on cancer cell lines was screened based on dose/time using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) was used to measure the mRNA expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Proliferating Cell Nuclear Antigen (PCNA) in each group. The percentage of apoptotic cells was evaluated using Annexin V/PI staining. RESULTS: Dopamine, cabergoline, thioridazine, and entacapone elicited cytotoxic effects on AGS and KATO-III cells in a dose-dependent manner and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. The expression of Bcl-2 and PCNA was significantly decreased, whereas the expression of Bax was considerably increased in the AGS and KATO-III cells compared to that in the blank group (p < 0.05); however, no similar effect was observed in MKN-45 cells. CONCLUSION: Through in vitro experiments, this study provides evidence that the antipsychotic drugs cabergoline, dopamine, thioridazine, and entacapone can inhibit gastric cancer growth in AGS and KATO-III cells. These findings suggest that these drugs could be repurposed as novel therapeutic agents for the treatment of gastric cancer.

Development, Optimization, and in vitro Evaluation of Silybin-loaded PLGA Nanoparticles and Decoration with 5TR1 Aptamer for Targeted Delivery to Colorectal Cancer Cells.

Chemotherapeutic agents often lack specificity, intratumoral accumulation, and face drug resistance. Targeted drug delivery systems based on nanoparticles (NPs) mitigate these issues. Poly (lactic-co-glycolic acid) (PLGA) is a well-studied polymer, commonly modified with aptamers (Apts) for cancer diagnosis and therapy. In this study, silybin (SBN), a natural agent with established anticancer properties, was encapsulated into PLGA NPs to control delivery and improve its poor solubility. The field-emission scanning electron microscopy (FE-SEM) showed spherical and uniform morphology of optimum SBN-PLGA NPs with 138.57±1.30nm diameter, 0.202±0.004 polydispersity index (PDI), -16.93±0.45mV zeta potential (ZP), and 70.19±1.63% entrapment efficiency (EE). The results of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) showed no chemical interaction between formulation components, and differential scanning calorimetry (DSC) thermograms confirmed efficient SBN entrapment in the carrier. Then, the optimum formulation was functionalized with 5TR1 Apt for active targeted delivery of SBN to colorectal cancer (CRC) cells in vitro. The SBN-PLGA-5TR1 nanocomplex released SBN at a sustained and constant rate (zero-order kinetic), favoring passive delivery to acidic CRC environments. The MTT assay demonstrated the highest cytotoxicity of the SBN-PLGA-5TR1 nanocomplex in C26 and HT29 cells and no significant cytotoxicity in normal cells. Apoptosis analysis supported these results, showing early apoptosis induction with SBN-PLGA-5TR1 nanocomplex which indicated this agent could cause programmed death more than necrosis. This study presents the first targeted delivery of SBN to cancer cells using Apts. The SBN-PLGA-5TR1 nanocomplex effectively targeted and suppressed CRC cell proliferation, providing valuable insights into CRC treatment without harmful effects on healthy tissues.

Repurposing naproxen as a potential nucleocapsid antagonist of beta-coronaviruses: targeting a conserved protein in the search for a broad-spectrum treatment option.

Ongoing mutations in the coronavirus family, especially beta-coronaviruses, raise new concerns about the possibility of new unexpected outbreaks. Therefore, it is crucial to explore new alternative treatments to reduce the impact of potential future strains until new vaccines can be developed. A promising approach to combat the virus is to target its conserved parts such as the nucleocapsid, especially via repurposing of existing drugs. The possibility of this approach is explored here to find a potential anti-nucleocapsid compound to target these viruses. 3D models of the N- and C-terminal domains (CTDs) of the nucleocapsid consensus sequence were constructed. Each domain was then screened against an FDA-approved drug database, and the most promising candidate was selected for further analysis. A 100 ns molecular dynamics (MD) simulation was conducted to analyze the final candidate in more detail. Naproxen was selected and found to interact with the N-terminal domain via conserved salt bridges and hydrogen bonds which are completely conserved among all Coronaviridae members. MD analysis also revealed that all relevant coordinates of naproxen with N terminal domain were kept during 100 ns of simulation time. This study also provides insights into the specific interaction of naproxen with conserved RNA binding pocket of the nucleocapsid that could interfere with the packaging of the viral genome into capsid and virus assembly. Additionally, the in-vitro binding assay demonstrated direct interaction between naproxen and recombinant nucleocapsid protein, further supporting the computational predictions.Communicated by Ramaswamy H. Sarma.

Neutrophil-to-lymphocyte, platelet-to-lymphocyte and lymphocyte-to-monocyte ratios, any association with metabolic syndrome?

Background: Metabolic syndrome is a critical health concern associated with an elevated risk of chronic health problems including cardiovascular disease and diabetes. There are shreds of evidence that novel inflammatory ratios including neutrophil-to-lymphocyte, platelet-to-lymphocyte and lymphocyte-to-monocyte ratios serve as prognostic biomarkers for metabolic syndrome (MetS). This hypothesis was investigated in a cohort of the Iranian population. Methods: selection of MetS + subjects was based on the National Cholesterol Education Program Adult Treatment Panel III criteria 3 (NCEP ATP 3). The control group consisted of participants negative for any of the five MetS criteria. Demographic and laboratory data were extracted from the Tabari cohort study. Results: A total of 1930 subjects including 965 Mets positive and 965 MetS criteria negative participants were evaluated. Diabetes (84.8%), hypertension (48.9%), hypertriglyceridemia (81.7%), low HDL cholesterol (70.3%), and high waist circumference (78.9%) were observed in patients. There were no differences between NLR (1.66±0.71 vs. 1.69±0.72 P=0.42), LMR (11.23±3.13 vs. 11.30±11.99, P= 0.86) and PLR (113.85±68.67 vs 114.11±35.85, P=0.91) between case and control groups, respectively. Logistic regression analysis revealed no association between ratios and MetS risk even after adjusting for potential confounders including age, gender, living place, and BMI. Conclusion: In a relatively large population from Northern Iran, no association was observed between CBC-derived inflammatory ratios and the presence of MetS.

Dopamine receptors gene overexpression in the microenvironment of invasive gastric cancer and its potential implications.

BACKGROUND: Gastric cancer (GC) is the fifth most common cancer worldwide and the most commonly diagnosed cancer in Iran. The nervous system provides proximity to tumor cells by releasing neurotransmitters such as dopamine and presenting them to the corresponding receptor-bearing tumors. While nerve fibers infiltrate the tumor microenvironment, little is known about the expression levels of dopamine (DA), dopamine receptors (DRs), and catechol-O-methyltransferase (COMT) in GC patients. METHODS: DRs and COMT expression were analyzed in 45 peripheral blood mononuclear cells (PBMCs) and 20 paired tumor and adjacent tissue of GC patients by quantitative polymerase chain reaction. DA was measured in plasma specimens using enzyme-linked immunosorbent assay. Protein-protein interaction analysis was carried out to identify GC-related hub genes. RESULTS: Increased expression of DRD1-DRD3 was found in tumor specimens compared with adjacent non-cancerous specimens (P < 0.05). A positive correlation was found between DRD1 and DRD3 expression (P = 0.009); DRD2 and DRD3 expression (P = 0.04). Plasma levels of dopamine were significantly lower in patients (1298 pg/ml) than in controls (4651 pg/ml). DRD1-DRD4 and COMT were up-regulated in PBMCs of patients compared with controls (P < 0.0001). Bioinformatic analyses showed 30 hub genes associated with Protein kinase A and extracellular signal-regulated kinase signaling pathways. CONCLUSIONS: The findings indicated dysregulation of DRs and COMT mRNA expression in GC and suggest that the brain- gastrointestinal axis may mediate gastric cancer development. Network analysis revealed that combination treatments could be considered for optimizing and improving the precision treatment of GC.

Serotonin Receptors and Acetylcholinesterase Gene Expression Alternations: The Potential Value on Tumor Microenvironment of Gastric Cancer.

INTRODUCTION: Gastric cancer is one of the common causes of cancer-related death in the world. Neurotransmitters have recently been related to the proliferation of cancer cells, but the role of neurotransmitters in the progression of gastric cancer is still unexplored. The cross-talk between the nervous system and immune cells through serotonin and its receptors in the tumor microenvironment can impact tumor progress. Our purpose is to expose probable changes in serotonin receptors, acetylcholinesterase, and monoamine oxidase A gene expression in gastric cancer. METHODS: Transcript of serotonin receptors (5-HTR2A, 5-HTR2B, 5-HTR3A, 5-HTR7) and monoamine oxidase A genes in the peripheral blood mononuclear cells (40 patients and 40 control) and tissue (21 tumors and 21 normal adjacent tissues) were assessed. The gene expression was analyzed by quantitative real-time PCR using suitable primers. Statistical analysis was performed using appropriate software (REST, Prism). RESULTS: Significantly higher amounts of 5-HTR2A, 5-HTR2B, 5-HTR3A, 5-HTR7, and acetylcholinesterase gene transcripts were found in the peripheral blood of gastric cancer patients compared with healthy individuals. The expression of 5-HTR2B and 5-HTR3A genes was significantly higher (p = 0.0250, p = 0.0005, respectively) and the acetylcholinesterase gene was lower in the tissue of patients (p = 0.0119) compared with adjacent normal tissue. CONCLUSION: This study highlights the role of serotonin receptors in gastric cancer that might have suggestions for the development of novel therapeutics and defensive approaches that target factors associated with the link between the nervous system, cancer cells, and the tumor microenvironment.

Significance of Serum Apelin Levels as a Biomarker for Gastric Cancer Diagnosis.

OBJECTIVES: Gastric cancer (GC) is one of the common lethal disease and the most common cancers worldwide and in Iran. North of Iran is known as a common area of gastric cancer and a high-risk zone in Iran. Apelin is a biomolecule that plays roles in various types of cancers. This study was designed to investigate the serum apelin-12 levels in patients with gastric cancer as a predictive marker and affordable noninvasive alternative. METHODS: In this case-control study, the case group included 42 patients with gastric cancer who were diagnosed by endoscopy and pathological findings. The participants in the case group were compared with the control group including 43 healthy individuals with no history of gastric cancer in their first-degree relatives and visiting the lab for routine tests. Apelin-12 serum level was assessed using ELISA kit. Data were analyzed in SPSS V16.0 applying Fisher's exact test, Mann-Whitney U test, and t-test. RESULTS: Serum apelin-12 in patients with gastric cancer was found to be statistically lower than that in healthy individuals (p< 0.05). There were no significant differences between clinicopathological characteristics and apelin-12 expression. The median survival time in experimental and control groups was 16.0 months. CONCLUSIONS: In the current study, serum levels of apelin were significantly different between cases and controls.

Mental health status and psychosocial issues during Nationwide COVID-19 quarantine in Iran in 2020: A cross-sectional study in Mazandaran Province.

The coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly, and its psychosocial impact remains a big challenge. In this respect, quarantine has been recommended, as a significant practice, to prevent the given condition. Therefore, the present study was to determine the prevalence rates of depression, anxiety, and stress and to reflect on the impact of COVID-19, as a traumatic stressor event, on individuals. This web-based survey was fulfilled via an online questionnaire, completed by respondents selected through the cluster sampling technique, from March 24 to April 10, 2020, living in Mazandaran Province, Northern Iran. Accordingly, the data regarding demographic characteristics, physical health status, quarantine compliance, contact with COVID-19, and additional information were collected. The psychosocial impact of the pandemic was then assessed by the Impact of Event Scale-Revised (IES-R), and the respondents' mental health status was evaluated using the Depression, Anxiety, and Stress Scale-21 (DASS-21). Data analysis was further performed by linear regression. The study findings, from 1075 respondents, revealed that 22.5% of the cases had moderate-to-severe depression, 38.5% of the individuals were suffering from moderate-to-severe anxiety, and 47.2% of the participants were experiencing moderate-to-severe stress. In 14.5% of the respondents, the psychosocial impact of COVID-19 also varied from the possibility of post-traumatic stress disorder (PTSD) to immunosuppression (p < 0.01). With the high prevalence rates of depression, anxiety, and stress, mental health professionals are suggested to develop psychosocial interventions and support plans for the general population to reduce the impact of the COVID-19 pandemic on public mental health status.

The Psychometric Properties of the Fear of Progression Questionnaire (FoP-Q) for Cancer Patients in Iran.

PURPOSE: Fear of progression or recurrence is assumed as a rational response to the threat of cancers and types of cancer treatment. However, the elevated levels of fear in cancer patients can become dysfunctional. Therefore, a valid and reliable questionnaire is unquestionably required for this purpose. This study aimed to translate the Fear of Progression Questionnaire and evaluate its psychometric properties for patients with gastrointestinal cancers in Iran. METHODS: In this study with a methodological research design, a total number of 430 patients affected with gastrointestinal cancers referring to Northern Iran completed the 43-item Fear of Progression Questionnaire. The psychometric properties of the questionnaire were evaluated, including the face validity and content validity. Then construct validity was assessed using exploratory and confirmatory factor analyses. Finally, the reliability was assessed using internal consistency (Cronbach's alpha) and stability (intraclass correlation coefficient). RESULTS: Based on the result of the face and content validity, no items were revised and removed. The five extracted factors included were emotional response, employment, and loss of independence, economy/family, and coping. These factors explained 37% of the total variance of Fear of Progression Questionnaire. Reliability (by Cronbach's alpha) and stability (test retest was evaluated by intraclass correlation coefficient) were more than 0.7. CONCLUSION: The study results revealed that the Persian version of the Fear of Progression Questionnaire had acceptable reliability and validity for cancer patients in Iran. Emotional responses explained the most variance of the concept of fear of progression among cancer patients.

Comparing mental health status and COVID-19 event impact between survivors and the general population during the second wave of the pandemic in Iran.

BACKGROUND AND AIM: The coronavirus disease 2019 (COVID-19) pandemic has to date overwhelmed the survivors and the general population. The present study aimed to compare the mental health status and the COVID-19 event impact between the survivors and the general population in Mazandaran Province, Northern Iran. DESIGN: A web-based cross-sectional survey was used. METHODS: This study was performed using convenience sampling. RESULTS: In total, 1,766 participants were included in this study. The findings revealed that the posttraumatic stress disorder (PTSD) severity in both outpatient and hospitalized groups was significantly higher than that in the general population. Besides, the levels of anxiety and depression in the group receiving inpatient care and treatment had significantly elevated than those in the general population. CONCLUSION: Given the high prevalence rate of mental disorders, healthcare professionals are recommended to plan for various interventions and support services to boost community mental health status.

Association between Serum Progastrin Biomarker Level and Gastric Cancer.

BACKGROUND AND OBJECTIVE: gastric cancer is the fifth most prevalent cancer and the fourth cause of death because of cancer. In Iran, northern and northwestern regions are considered gastric cancer hot spots. Identifying serum biomarkers could be helpful in early diagnosis of patients with gastric adenocarcinoma (GAC). Increase in progastrin level has been reported in different cancers. Given the diagnostic value of this biomarker, this study aimed to determine the diagnostic role of progastrin serum biomarker in patients with gastric cancer. METHODOLOGY: In this case-control study, forty patients with gastric cancer who were diagnosed by endoscopy and pathologic findings and visited Mazandaran Comprehensive Cancer Center. The participants had received no treatment yet and entered this study. The participants in case group were compared with the control group including forty-two individuals with no history of gastrointestinal cancer in their first-degree relatives and visiting the lab for routine tests. Progastrin serum level was assessed using ELISA kit. The Kruskal-Wallis test and Mann Whitney test, both non-parametric) were used for statistical analysis and the relation between the variables was examined using Pearson's correlation coefficient at 95% confidence level in SPSS 16. FINDINGS: In this study, progastrin serum level was significantly higher in patients with gastric cancer compared with normal participants (P = 0.035). Progastrin serum level had no significant relation with tumor clinicopathologic parameters (p-value > 0.05). CONCLUSION: Increase in progastrin may be utilized as a predictive factor for gastric cancer.

Effects of Vitamin E on Doxorubicin Cytotoxicity in Human Breast Cancer Cells in Vitro.

OBJECTIVE: This study aimed to evaluate in vitro synergistic anticancer effect of doxorubicin combined with Vitamin E. METHODS: The MTT assay was utilized to assess the cytotoxicity of Vitamin E and vitamin E combined with doxorubicin and vital activities of SKBR3, MDA-MB-231, and HFF cells over a 24-hour incubation period. In addition, the antioxidant properties of these interventions and the decrease of reactive oxygen species (ROS) content caused by the treatment were evaluated. RESULTS: The antiproliferative effect of doxorubicin increased significantly in combination with vitamin E (Doxcorobicin 2µM vs. Vitamin E 120µM, P=0.000). Despite reducing cell ROS content due to vitamin E treatment, the combination of vitamin E and doxorubicin showed no significant synergistic effect (Doxcorobicin 2µM vs. Vitamin E 120µM, P=0.998). CONCLUSION: This study indicated that the doxorubicin-vitamin E treatment reduced the viability of breast cancer cells with the minimum side effects on normal cells. In addition, the high dosage of vitamin E intensified the cytotoxicity of doxorubicin.

Differential gene expression of SARS-CoV-2 transcriptome provides insight into the design of more sensitive diagnostic tests.

The Coronavirus disease 2019 (COVID-19) pandemic is being addressed through RT-PCR, a frontline diagnostic technique. We evaluated gene expression patterns to improve the accuracy and sensitivity of current diagnostic tests. We downloaded relevant next-generation sequencing (NGS) data from the Sequence Read Archive (SRA) database, checked for quality, and mapped them onto the target reference sequence. It was determined that ORF1ab, N, S, and ORF8 genes are mainly expressed based on the results of the quantitative evaluation after normalization by HPRT and elimination of insufficient expression data. ORF8, ORF3a, and M genes were found to have higher expression values than the E gene as a routine RT-PCR detector gene (p*0.05). M gene expression values are also close to ORF8 values. Taking into account the importance of differential expression of genes in the design of diagnostic kits as well as the findings of from this study, it is likely that the M gene is worth further investigation due to its high expression and low mutation rate.

Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial.

This trial aims to evaluate the effectiveness of adding melatonin to the treatment protocol of hospitalized coronavirus disease 2019 (COVID-19) patients. This was an open-label, randomized controlled clinical trial in hospitalized COVID-19 patients. Patients were randomized into a treatment arm receiving melatonin plus standard care or a control arm receiving standard care alone. The trial's primary endpoint was sleep quality examined by the Leeds Sleep Evaluation Questionnaire (LSEQ). The trial's secondary endpoints were symptoms alleviation by Day 7, intensive care unit admission, 10-day mortality, white blood cell count, lymphocyte count, C-reactive protein status, and peripheral capillary oxygen saturation. Ninety-six patients were recruited and allocated to either the melatonin arm (n = 48) or control arm (n = 48). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms on Day 7. The mean of the LSEQ scores was significantly higher in the melatonin group (p < 0.001). There was no significant difference in laboratory data, except for blood oxygen saturation, which has improved significantly in the melatonin group compared with the control group (95.81% vs. 93.65% respectively, p = 0.003). This clinical trial study showed that the combination of oral melatonin tablets and standard treatment could substantially improve sleep quality and blood oxygen saturation in hospitalized COVID-19 patients.

Association between liver enzymes and metabolic syndrome: results of the enrollment phase of Tabari cohort.

BACKGROUND: The association between liver enzymes and metabolic syndrome (MetS) has been evaluated in several studies with different results. The purpose of this study is to determine the association between the serum levels of these liver enzymes and MetS in Tabari cohort population. METHOD: In this case-control study, data collected from the enrolment phase of the Tabari cohort population have been used. MetS was defined based on IDF (international diabetes federation) standards. Then, 476 patients with MetS (case group) and 476 age-sex matched controls were selected randomly. RESULTS: Mean aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were higher in case group than control group (20.59 vs. 19.99 respectively, p = 0.339 and 24.64 vs. 20.16 respectively, p < 0.001). The chance of having MetS, high triglyceride, and fasting blood glucose (FBG) was significantly higher in people with ALT ≥ 40 (1.63, 2.35, and 2.02, respectively). The chance of having MetS in people with AST ≥ 40 was 1.45 times higher than that among those with normal AST level (p > 0.05). CONCLUSION: This study showed that there is an association between liver enzymes and MetS as well as some of its components. Liver enzymes, especially ALT, can be used as an early indicator of MetS in the at risk population.

Side effects and Immunogenicity following administration of the Sputnik V COVID-19 vaccine in health care workers in Iran.

The Sputnik V is a COVID- 19 vaccine developed by the Gamalia institute of epidemiology and microbiology and released on August 11, 2020. We provided independent evidence on side effects and immunogenicity following the administration of the Sputnik V COVID-19 in Iran. In this observational study, the healthcare workers who were vaccinated with the Sputnik V COVID-19 vaccine within February and April 2021 were evaluated. Among a total of 13,435 vaccinated healthcare workers, we received 3236 self-declaration reports of Sputnik V associated adverse events with the mean age 39.32 ± 10.19 years old which 38.8% were men and 61.2% were women. Totally 68.8% of females versus 66.2% of males reported side effects after receiving the first dose and 31.2% of females versus 33.8% of males reported side effects after the second dose of vaccine. The most common side effect was a pain in the injection site (56.9%), fatigue (50.9%), body pain (43.9%), headache (35.7%), fever (32.9%), joint pain (30.3%), chilling (29.8%) and drowsiness (20.3%). Side effects of the vaccine were significantly more frequent in females and younger individuals. Among a total of 238 participants, more than 90% after the first and second dose of vaccine had a detectable level of SARS-CoV-2 RBD antibody and SARS-CoV-2 neutralizing antibody. Although the overall rate of adverse effects was higher than the interim results from randomized controlled trials, our findings support the manufacturer's reports about the high humoral immunogenicity of vaccine against COVID-19.

Improvement in use of best practice in the care of patients with oral mucositis in a comprehensive cancer center in Iran: a best practice implementation case study.

INTRODUCTION: Oral mucositis is a common debilitating complication of cancer treatments, particularly chemotherapy and radiation. OBJECTIVES: The purpose of this study was to improve oral mucositis prevention and control among cancer patients through the implementation of best practice guidelines in a tertiary referral center in Northern Iran. METHODS: A clinical audit design was utilized in this implementation project. A preimplementation audit was conducted against nine best practice criteria for the prevention and treatment of oral mucositis among new cases of cancer patients in November and December 2019. Fifty cancer patients and 20 nurses participated in this phase of the clinical audit. The next step included a facilitated multidisciplinary focus group identifying targeted strategies and implementing them, completed in late December 2019. A postimplementation audit was then conducted on another 50 cancer patients and the same 20 nurses in January and early February 2020. The project utilized the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice software. RESULTS: The preimplementation audit revealed gaps between the current practice and best practice across eight of the nine criteria. After implementing the targeted strategies, the outcomes improved across most of the criteria in the follow-up audit: 80% increase was observed in compliance of staff education, 100% increase in providing standard oral hygiene protocol in place, 64% increase in carrying out a dental examination and conducting initial oral cavity examination, and also 34% increase in conducting of ongoing oral cavity examination by a dentist, and finally 100% increase in providing preventive and therapeutic oral care regimens in place and oral pain assessment using a validated tool. CONCLUSION: The results of this project indicate that clinical auditing is an effective approach to the assessment of evidence-based care practices for oral mucositis among new cancer patients. Evidence-based oral mucositis management among cancer patients can be achieved by educating the patients and nursing staff using the newest guidelines and dentists' comprehensive dental and oral hygiene examinations.

Lymphopenia and lung complications in patients with coronavirus disease-2019 (COVID-19): A retrospective study based on clinical data.

A rapid outbreak of novel coronavirus, coronavirus disease-2019 (COVID-19), has made it a global pandemic. This study focused on the possible association between lymphopenia and computed tomography (CT) scan features and COVID-19 patient mortality. The clinical data of 596 COVID-19 patients were collected from February 2020 to September 2020. The patients' serological survey and CT scan features were retrospectively explored. The median age of the patients was 56.7 ± 16.4 years old. Lung involvement was more than 50% in 214 COVID-19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ± 10.16 (normal range, 20%-50%). Although the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in more than 80% of COVID-19 patients; CRP, ESR, and platelet-to-lymphocyte ratio (PLR) may not indicate the in-hospital mortality of COVID-19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio, 9.24; 95% confidence interval, 4.32-19.78). These results indicated that lymphopenia < 20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in-hospital mortality rate of this group was significantly higher than other COVID-19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (p = .00). Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient's mortality. These could act as laboratory and clinical indicators of disease severity, mortality, and outcome.

A promising and effective platform for delivering hydrophilic depigmenting agents in the treatment of cutaneous hyperpigmentation: kojic acid nanostructured lipid carrier.

This study was aimed at preparing and characterising kojic acid nanostructured lipid carriers (KA-NLCs) for delivery to skin. KA-NLCs were prepared using high-speed homogenization followed by ultra-probe sonication method. KA-NLCs were optimized by glyceryl mono-stearate (GMS) and cholesterol (Chol) as solid lipid excipients, oleic acid (OA) as liquid lipid excipient, span 60 (SP 60) and Tween 20 (Tw 20) as co-emulsifiers. For optimized formulation (KA-NLC3), values of particle size, encapsulation efficiency, drug loading, polydispersity index (PDI) and zeta potential (ZP) were found to be 172.9 ± 7.1 nm, 76.4 ± 0.1%, 17.6 ± 1.3%, 0.3 ± 0.1 and -39.1 ± 2.7 mV, respectively. KA-NLC3 was stable at 4 °C and 25 for 3 months. TEM image confirmed these results. ATR-FTIR, DSC and PXRD results indicated suitable entrapment of KA in NLCs without any chemical interaction. The release profile of KA-NLC3 followed a sustained pattern. KA-NLC3 has potent tyrosinase inhibitory activity in comparison with pure KA. Nanoparticles showed a higher antioxidant activity than pure KA. The results of the ex vivo and in vitro percutaneous absorption showed that KA-NLC3 improved percutaneous delivery of KA. Concentrations below 250 µg/mL were determined as suitable concentrations for KA-NLC3. It seems to be biocompatible formulation for the cosmetics aims.

Sofosbuvir and daclatasvir for the treatment of COVID-19 outpatients: a double-blind, randomized controlled trial.

INTRODUCTION: Effective treatments are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). This trial aims to evaluate sofosbuvir and daclatasvir versus standard care for outpatients with mild COVID-19 infection. METHODS: This was a randomized controlled clinical trial in outpatients with mild COVID-19. Patients were randomized into a treatment arm receiving sofosbuvir/daclatasvir plus hydroxychloroquine or a control arm receiving hydroxychloroquine alone. The primary endpoint of the trial was symptom alleviation after 7 days of follow-up. The secondary endpoint of the trial was hospital admission. Fatigue, dyspnoea and loss of appetite were investigated after 1 month of follow-up. This study is registered with the IRCT.ir under registration number IRCT20200403046926N1. RESULTS: Between 8 April 2020 and 19 May 2020, 55 patients were recruited and allocated to either the sofosbuvir/daclatasvir treatment arm (n = 27) or the control arm (n = 28). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms at Day 7. One patient was admitted to hospital in the sofosbuvir/daclatasvir arm and four in the control arm, but the difference was not significant. After 1 month of follow-up, two patients reported fatigue in the sofosbuvir/daclatasvir arm and 16 in the control arm; P < 0.001. CONCLUSIONS: In this study, sofosbuvir/daclatasvir did not significantly alleviate symptoms after 7 days of treatment compared with control. Although fewer hospitalizations were observed in the sofosbuvir/daclatasvir arm, this was not statistically significant. Sofosbuvir/daclatasvir significantly reduced the number of patients with fatigue and dyspnoea after 1 month. Larger, well-designed trials are warranted.