The role of dysregulated immune responses in COVID-19 pathogenesis.

The coronavirus disease-2019 (COVID-19) which caused by severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), is a pandemic threat to global public health. It has a wide spectrum of clinical manifestations from mild to critical illness, the most serious of which is the complications of acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection appears mild in infants and children, however, in adults, it can lead to serious consequences. In this review, we highlighted the differences between the immune responses of the lung in children and adults, immune dysregulation and their possible role in clinical manifestations in COVID-19. There is a reduction in population of immunocompetent cells during aging and subsequently induced ineffective inflammation in the faces of some infections. Dysregulation in the immune system can lead to an unappropriated local and systemic immune responses and subsequently the rapid spread of the virus, leading to severe COVID-19 disease. Therefore, recognizing the differences in the immune responses of various hosts as well as to improve the immune system disorder should always be part of research and treatment protocols.

Improvement of chemotherapy through reducing of cachexia by using Citrus unshiu peel extract.

ETHNOPHARMACOLOGICAL RELEVANCE: .Colorectal cancer (CRC) is now one the fourth cause of mortality and morbidity due to cancer throughout the globe. Cachexia is more prevalent in patients with this cancer and has a negative effect on response to chemotherapy and radiotherapy. Inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 could play a key role in cachexia. Moreover strong chemotherapy medications such as doxorubicin have complications such as toxicity and cachexia. Citrus unshiu Peel have been used as traditional herbal drugs for the treatment of cancer in traditional oriental medicine (TOM). Since its main components have anti-inflammatory effects, we evaluated the anti-cachexia activity in order to support the traditional usage of Citrus unshiu peel. Aim of the study; We aimed to assess the preventive or therapeutic effect of Citrus unshiu Peel Extract (CUPE) on cachexia by reducing of inflammatory cytokines in mice bearing C26 tumor. Also the contribution role of CUPE has evaluated on improvement of chemotherapy through reducing of inflammatory cytokines. Materials and Methods; The CUPE was prepared by Soxhlet extractor and quantitative and qualitative analysis of aqua extract was performed by high performance liquid chromatography (HPLC). C26 tumor bearing BALB/c male mice were immunized with different formulation of oral Prophylactic-therapeutic CUPE and/or intraperitoneal doxorubicin and then were monitored for weight gain, food intake and tumor size throughout the study. On the 32nd day after tumor injection, inflammatory cytokines levels, IL6, TNF-α and IL-1ß were evaluated by Enzyme-linked Immunosorbent Assay (ELISA) and Malondialdehyde- Thiobarbituric acid (MDA) levels were measured by standard method. Results; Oral administration of CUPE in both prophylactic and therapeutic formulation to C26 adenocarcinoma bearing mice reduced the weight loss, tumor volume, and serum MDA levels compared with untreated tumor-bearing mice and Doxorubicin (Dox) groups. Also, the combination therapy of (CUPE + Dox) leads to reducing the levels of serum IL-6, TNF-α, IL-1ß and tumor volume compared with untreated tumor-bearing mice and Dox groups. Serum MDA levels were considerably reduced by combination therapy of (CUPE + Dox) compared with Dox groups. Conclusions; These findings confirm the safety and efficacy of CUPE on C26 adenocarcinoma bearing mice as pure and adjuvant therapy, the results of which might be used in further human studies as a valuable natural anticancer agent alone or in combination with chemotherapy. Also the results showed that simultaneous application of CUPE and Dox leads to significant reduction of cachexia from the Dox chemotherapy.