Background: The ongoing outbreak of SARS-CoV-2 represents a significant challenge to international health. Several reports have highlighted the importance of ACE2 on the pathogenesis of COVID-19. The spike protein of SARS-CoV-2 efficiently binds to the angiotensin-converting enzyme 2 (ACE2) receptors and facilitates virus entry into the host cell. In the present study, we hypothesize that a functional insertion/deletion polymorphism-rs4646994 I/D and rs4240157 T > C in the ACE gene could be associated with SARS-CoV-2 infection and mortality. Methodology: This study included 117 consecutive COVID-19 patients and 150 age matched healthy controls (ACE2-rs4646994 I/D) and 100 age matched healthy controls with ACE2 rs4240157 T > C. We used Mutation specific PCR (MSP) for ACE2-rs4646994 I/D genotyping and amplification refractory mutation system (ARMS-PCR) for ACE2 rs4240157 T > C genotyping. Results: Results indicated that there were significant differences in the genotype distributions of ACE2-rs4646994 I/D polymorphisms (p < 0.030) and ACE2 rs4240157 T > C between COVID-19 patients and controls (p-values < 0.05). Higher frequency of DD genotype (48.71%) and D allele (0.67) was reported in COVID-19 patients than controls. Our results showed that the ACE2-DD genotype was strongly associated with increased COVID-19 severity (OR 2.37 (95%) CI = (1.19–4.70), RR = 1.39 (1.09–1.77), p < 0.013) and also a strong association was seen with ACE2-ID genotype with COVID-19 severity (OR 2.20 (95%) CI = (1.08–4.46), p < 0.020) in the codominant model. In allelic comparison, the D allele was strongly associated with COVID-19 severity (OR 1.58 (95% CI) (1.11–2.27), RR 1.21 (1.05–1.41) p < 0.010). A significant correlation of ACE2-I/D genotypes was reported with Age (p < 0.035), T2D (p < 0.0013), hypertension (p < 0.0031) and coronary artery disease (p < 0.0001). Our results indicated ACE2-DD genotype was strongly associated with increased COVID-19 mortality (OR 8.25 (95%) CI = (2.40 to 28.34), p < 0.008) and also ACE2-DD + DI genotype was strongly associated with increased COVID-19 mortality with OR 4.74 (95%) CI = (1.5214 to 14.7915), p < 0.007. A significant correlation was reported between COVID-19 patients and age matched controls (p < 0.0007). Higher frequency of heterozygosity TC (40%) followed by ACE2-CC genotype (24.78%) was reported among COVID-19 patients. Using multivariate analysis, ACE2–CT genotype was strong associated with SARS-CoV-2 severity with an OR 2.18 (95% CI) (1.92–3.99), p < 0.010 and also ACE2–CC genotype was linked with COVID-19 severity with an OR 2.66 (95% CI) (1.53–4.62), p < 0.005. A significant correlation of ACE2-T > C genotypes was reported with gender (p < 0.04), T2D (p < 0.035). ACE2-CC genotype was strongly associated with increased COVID-19 mortality OR 3.66 (95%) CI = (1.34 to 9.97), p < 0.011 and also ACE2-C allele was associated with COVID-19 mortality OR 2, 01 (1.1761–3.45), p < 0.010. Conclusions: It is concluded that ACE-DD genotype and D allele was strongly associated with increased COVID-19 patient severity. In addition, ACE I/D polymorphism were strongly associated with advanced age, diabetes and ischemic heart disease in COVID-19 patients whereas ACE-II genotype was a protective factor against the development of severe COVID-19. ACE2-DD genotype was strongly associated with increased COVID-19 mortality. Additionally, ACE2–CC and CT genotypes were strongly associated with COVID-19 severity. Therefore, our study might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.

The study of wound‑healing plants has acquired an interdisciplinary nature with a systematic investigational approach. Several biochemicals are involved in the healing process of the body, including antioxidants and cytokines. Although several pharmaceutical preparations and formulations are available for wound care and management, it remains necessary to search for efficacious treatments, as certain current formulations cause adverse effects or lack efficacy. Phytochemicals or biomarkers from numerous plants suggest they have positive effects on different stages of the wound healing process via various mechanisms. Several herbal medicines have displayed marked activity in the management of wounds and various natural compounds have verified in vivo wound healing potential, and can, therefore, be considered as potential drugs of natural origin. Chromolaena odorata (L.) R.M. King and H. Robinson is considered a tropical weed. However, it exhibits anti‑inflammatory, antipyretic, analgesic, antimicrobial, cytotoxic and numerous other relevant medicinal properties on an appreciable scale, and is known in some parts of the world as a traditional medicine used to treat various ailments. To understand its specific role as nature's gift for healing wounds and its contribution to affordable healthcare, this plant must be scientifically assessed based on the available literature. This review aims to summarize the role of C. odorata and its biomarkers in the wound healing activities of biological systems, which are crucial to its potential future drug design, development and application for the treatment of wounds.

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.Aim of the work: This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.Patients and methods: This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.Results: The main symptoms among the included patients were: fever (96.87%), cough (93.75%), dyspnea (90.62%), sore throat (75%), runny nose (75%), sputum (50%), headache (43.75%), myalgia (40.62%), chest pain (37.50%), hemoptysis (37.50%), nausea and vomiting (34.37%), abdominal pain (21.87%) and diarrhea (15.62%). The presence of abdominal symptoms is significantly (P < 0.05) associated with bad prognosis. Out of the included 32 patients, 18 patients (56.25%) survived and 14 patients (43.75%) expired. There was a statistically significant difference in the duration of symptoms before hospitalization, mechanical ventilation and ICU and total hospital stay between the expired group and survivors (P < 0.01). Current smoking and smoking severity were statistically significantly (P < 0.01) higher in the expired group compared to survivors. Also, there was a statistically (P < 0.05) significant positive correlation between mortality and smoking severity (r = 0.640). Most of the expired patients presented with bilateral pulmonary infiltrates or unilateral infiltrates, but most of the survivors presented with normal This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). radiology or increased bronchovascular markings, and this difference in the results was statistically highly significant (P < 0.01). There were statistically highly significant (P < 0.01) differences in the mean values of APACHE II score (21.11 ± 3.70 vs 24.21 ± 3.82), SOFA score (5.83 ± 2.64 vs 8.85 ± 2.17) and CPIS (7.55 ± 1.14 vs 8.64 ± 1.39) between the expired group and survivors respectively. Also, there was a statistically significant decrease in PH, PaO 2 , O 2 saturation and HCO 3 (P < 0.05) among the expired group in comparison with the survivors, but no statistical difference regarding PaCO 2 (P > 0.05). There was a statistically significant positive correlation between mortality and old age (r = 0.633), obesity (r = 0.712), diabetes mellitus (r = 0.685), renal failure (r = 0.705), chronic heart diseases (0.591), COPD (r = 0.523), malignancy (r = 0.692), kidney...

BACKGROUND:Ziziphus jujuba belongs to family Rhamnaceae widely distributed in subtropical and tropical countries. It is used traditionally for several pharmacological purposes including anti-inflammation, antidiarrhoeal and antibacterial, as well as tonic and sometimes as hypnotic (sedative).AIM:To determine the in vivo antidiarrhoeal, antibacterial and anti-inflammatory activities of Z. jujuba fruit ethanolic extract.METHOD:The fruit was macerated and extracted by 95% (v/v) ethanol. The antidiarrhoeal activity was evaluated using castor oil and Escherichia coli induced diarrhoea mouse model. The antidiarrhoeal and antibacterial activity was investigated at graded doses (400-1200 mg/kg). The anti-inflammatory effects were tested using the carrageenan-induced paw oedema in female Wistar rats. Rat’s treatment groups received tragacanth, 100 mg/kg diclofenac sodium, 800 mg/kg, 1200 mg/kg or 1600 mg/kg of an ethanolic extract of Z. jujuba (EEZJ). All treatment groups were fed with the compounds one hour before carrageenan injection at of rat’s paw. Also, the EEZJ was further analysed by HPLC-PDA system for identification of the presence of betulinic acid and quercetin.RESULTS:EEZJ different doses did not show inhibitory activity against castor oil induced diarrhoea except for the higher (1200 mg/kg) dose. However, the frequency of defecation of stools and watery stool were reduced significantly when compared to control group (P ≤ 0.05 and P ≤ 0.01 respectively), resulted in overall 67% inhibition of diarrhoea. Our anti-inflammatory results demonstrated that EEZJ was able to inhibit the carrageenan-induced paw oedema in rats to a significant degree (p ≤ 0.05) and the paw volume and thickness of both left and right paw were affected compared to the negative control group.CONCLUSION:EEZJ possesses antidiarrhoeal and antibacterial activity in a dose depending manner and may provide a pharmacological basis for its clinical use in diarrheal diseases. The activity may partially be due to the presence of betulinic acid and quercetin.

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BACKGROUND:Methotrexate (MTX) is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA); however, it causes many side effects, including pulmonary lesions. In this review, we characterised the histopathological features of MTX-induced pulmonary lesions in RA patients.AIM:We carried out an electronic search of the relevant literature published during the period from 1990 to 2016. We included only the cases with definitive histo-pathological findings caused by MTX therapy.MATERIAL AND METHODS:The total number of cases is 27. Male: female ratio was 1:3, and ages ranged from 48 to 87 years old, with a mean (SD) = 65.7 (1.0). The cases were originally from Asia (55%), Europe (41%), and America (4%). The major complications of methotrexate therapy were lymphoproliferative disorders (42%) followed by interstitial fibrosis (33), and infections (25%). The incidence of these complications significantly increases with the duration of MTX treatment (p = 0.044). Among the infections, the most common causative organism was pneumocystis jiroveci. The majority of patients who developed infections following methotrexate therapy were from Europe whereas the majority of those who developed lymphoproliferative disorders were from Asia (p = 0.003).CONCLUSION:In conclusion, methotrexate therapy in rheumatoid arthritis patients causes different types pulmonary complications.

Genetic susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality continues to evolve. This report presents a case of an apparently healthy male adult who developed severe coronavirus disease 2019 (COVID-19) and a study on relevant genetic mutations, namely, angiotensin-converting enzyme 2 (ACE2-rs4646994 I/D) gene, glutathione S-transferase (GST) M1 and T1 gene, and miR-423 rs6505162 C>A gene polymorphism. Results showed that the ACE-DD genotype of ACE2, (GSTM1+/+) (GSTT1−/−) genotype of GST gene, and CA genotype (heterozygosity) of miR-423 rs6505162 genes, which were found in the patient, could be independent risk factors of severe COVID-19, even without comorbidities.

Background: Immune dysregulation has been linked to morbidity and mortality in COVID-19 patients. Understanding the immunology of COVID-19 is critical for developing effective therapies, diagnostics, and prophylactic strategies to control the disease. Aim: The aim of this study was to correlate cytokine and chemokine serum levels with COVID-19 disease severity and mortality. Subjects and Methods: A total of 60 hospitalized patients from the Tabuk region of Saudi Arabia with confirmed COVID-19 were included in the study. At hospital admission, the IL-1 β, IL-2, IL-8, IL-10, LT-B4, and CCL-2 serum levels were measured. The cytokine levels in COVID-19 patients were compared to the levels in 30 healthy matched control subjects. Results: The IL-1 β, IL-2, LTB-4, CCL-2, and IL-8 levels (but not IL-10) were significantly higher in all COVID-19 patients (47 survivors and 13 non-survivors) compared with the levels in the healthy control group. In the non-survivor COVID-19 patients, patients’ age, D-dimer, and creatinine kinase were significantly higher, and IL-1 β, IL-2, and IL-8 were significantly lower compared with the levels in the survivors. Conclusion: Mortality rates in COVID-19 patients are associated with increased age and a failure to mount an effective immune response rather than developing a cytokine storm. These results warrant the personalized treatment of COVID-19 patients based on cytokine profiling.