Identification, characterization, and prognosis investigation of pivotal genes shared in different stages of breast cancer.

One of the leading causes of death (20.1 per 100,000 women per year), breast cancer is the most prevalent cancer in females. Statistically, 95% of breast cancer are categorized as adenocarcinomas, and 55% of all patients may go into invasive phases; however, it can be successfully treated in approximately 70-80% of cases if diagnosed in the nascent stages. The emergence of breast tumor cells which are intensely resistant to conventional therapies, along with the high rate of metastasis occurrence, has highlighted the importance of finding novel strategies and treatments. One of the most advantageous schemes to alleviate this complication is to identify the common differentially expressed genes (DEGs) among primary and metastatic cancerous cells to use resultants for designing new therapeutic agents which are able to target both primary and metastatic breast tumor cells. In this study, the gene expression dataset with accession number GSE55715 was analyzed containing two primary tumor samples, three bone-metastatic samples, and three normal samples to distinguish the up- and down regulated genes in each stage compared to normal cells as control. In the next step, the common upregulated genes between the two experimental groups were detected by Venny online tool. Moreover, gene ontology, functions and pathways, gene-targeting microRNA, and influential metabolites were determined using EnrichR 2021 GO, KEGG pathways miRTarbase 2017, and HMDB 2021, respectively. Furthermore, elicited from STRING protein-protein interaction networks were imported to Cytoscape software to identify the hub genes. Then, identified hub genes were checked to validate the study using oncological databases. The results of the present article disclosed 1263 critical common DEGs (573 upregulated + 690 downregulated), including 35 hub genes that can be broadly used as new targets for cancer treatment and as biomarkers for cancer detection by evaluation of expression level. Besides, this study opens a new horizon to reveal unknown aspects of cancer signaling pathways by providing raw data evoked from in silico experiments. This study's outcomes can also be widely utilized in further lab research since it contains diverse information on common DEGs of varied stages and metastases of breast cancer, their functions, structures, interactions, and associations.

Evaluating the immunogenicity of gold nanoparticles conjugated RBD with Freund's adjuvant as a potential vaccine against SARS-CoV-2.

BACKGROUND: and Introduction: SARS-CoV-2 is currently considered as the most challenging issue in the field of health and medicine by causing a global pandemic. Vaccines are counted as a promising candidate to terminate this deadly pandemic. Various structural proteins in SARS-CoV-2 have recently drawn attention to be utilized as candidate vaccines to stimulate immune responses against COVID-19. MATERIALS AND METHODS: In current study, the RBD protein was cloned and expressed in E. coli host. Then, the expressed RBD protein was purified and its characterizations were evaluated through various methods. Gold nanoparticles, which were utilized as a carrier for candidate Nano-vaccine, were synthesized via oxidation-reduction reaction. While Gold NPs-conjugated RBD was injected into the second treatment group, in the first candidate vaccine, RBD was injected into the first treatment group solely. Complete and Incomplete Freud's Adjuvant were also utilized for both treatment groups to enhance the immune responses against RBD antigen. Immunizations were repeated 2 times in 14-day intervals to boost the immune system of BALB/c mice. The humoral and cell-mediated immune responses were examined through immune and cytokine assays. RESULTS: Our outcomes demonstrate that strong short-term humoral immunity (IgM) was induced in both the first and second treatment group, while long-term humoral responses (IgG) were only observed in the second treatment group. While stronger short- and long-term humoral (IgM and IgG, respectively) were observed in the second treatment group, particular cytokines production (TNF-ɑ and IFN-γ) as a marker of cell-mediated responses were significantly higher in the first treatment group. DISCUSSION AND CONCLUSION: Our study results show the high potentiality of RBD protein as an appropriate stimulating antigen in vaccine synthesis and testifies RBD-based candidate vaccines to control the COVID-19 pandemic. Our outcomes also recommend that Nano-vaccines can be more suitable candidates when stronger long-term immune responses matter.

Relationship between blood clots and COVID-19 vaccines: A literature review.

SARS-CoV-2 pandemic is one of the most critical pandemics during human civilization. Several therapeutic strategies for COVID-19 management have been offered; nonetheless, none of them seems to be sufficiently beneficial. In effect, vaccines have been proffered as a viable option. The critical issue now is to concentrate on protecting individuals against illness through immunization. One of the causes for concern among the researchers, physicians, and generally the whole community from the onset of vaccination has been the adverse effects (specifically blood clots) that may be observed after the injection of the COVID-19 vaccine. In some countries, such concerns have even resulted in the temporary or permanent discontinuation or abandonment of the application of some vaccines (especially AstraZeneca and Janssen). By evaluating rigorous studies published on this subject, the present article is aimed at identifying the association between blood clot incidence and COVID-19 vaccination. Various methods for producing the COVID-19 vaccines are analyzed, along with their possible pros and cons as well as common and rare side effects, especially VITT and blood clots. Finally, the differences of various vaccines on thrombotic events, WHO recommendations for VITT treatment, and blood clots statics are discussed.

COVID-19 in patients with and without acute kidney injury.

BACKGROUND AND OBJECTIVE: SARS-CoV-2 as the newest member of Beta-Coronaviruses can cause a complicated disease called COVID-19. This virus is able to penetrate a broad range of human cells, such as liver, heart, and kidney cells via ACE2-associated endocytosis. Heart involvement can result in kidney injuries; it is now testified that kidney congestion occurs following the cardio-renal syndrome. Acute Kidney Injury is one of the most critical damages to the kidney in a wide range of COVID-19-caused kidney injuries (which includes proteinuria, hematuria, etc.). Examination of AKI risk factors in COVID-19 patients can assist physicians to prevent its incidence. The final aim of this systematic review was to collate the condition and risk factors of AKI and non-AKI COVID-19 patients and to investigate AKI incidence in high-risk patients. METHOD: A complete and comprehensive survey was performed by reviewing original articles and case reports indexed in various databases such as PubMed/Medline, Embase, and WoS to find appropriate articles. The eligible articles then were selected by two authors and entered into the evaluation process. This systematic review conforms PRISMA statement. RESULTS: After searching for potentially relevant articles, 14 out of the initial 463 articles from 6 countries were selected and evaluated. All of eligible articles have investigated the rate of AKI incidence and its physio-pathological consequences in COVID-19 patients in all conditions (not only patients in critical condition). First, the initial differences between AKI and non-AKI patients were compared. As an instance, our study revealed that mean of White Blood cells (WBC) was much higher in AKI patients which can be responsible for the severe conditions. Then, other variations like differences in laboratory and imaging findings were compared between these two groups. Our outcomes demonstrated that the presence of diabetes mellitus (DM), hypertension (HTN), and male sex can be three significant risk factors in AKI incidence in COVID-19 patients. Fatality rate and treatment methods were also compared among these two groups. CONCLUSION: As one of kidney damages, AKI can worsen COVID-19 patients' status by causing conditions such as acidosis. Our study shows the common symptoms in AKI COVID-19 patients were fever, cough, and malaise. The results of our study can help physicians to arrange COVID-19 with AKI patients' treatment strategy precisely (Tab. 8, Fig. 1, Ref. 48).

Immunomodulatory agents for COVID-19 treatment: possible mechanism of action and immunopathology features.

The novel coronavirus pandemic has emerged as one of the significant medical-health challenges of the current century. The World Health Organization has named this new virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first detection of SARS-CoV-2 in November 2019 in Wuhan, China, physicians, researchers, and others have made it their top priority to find drugs and cures that can effectively treat patients and reduce mortality rates. The symptoms of Coronavirus Disease 2019 (COVID-19) include fever, dry cough, body aches, and anosmia. Various therapeutic compounds have been investigated and applied to mitigate the symptoms in COVID-19 patients and cure the disease. Degenerative virus analyses of the infection incidence and COVID-19 have demonstrated that SARS-CoV-2 penetrates the pulmonary alveoli's endothelial cells through Angiotensin-Converting Enzyme 2 (ACE2) receptors on the membrane, stimulates various signaling pathways and causes excessive secretion of cytokines. The continuous triggering of the innate and acquired immune system, as well as the overproduction of pro-inflammatory factors, cause a severe condition in the COVID-19 patients, which is called "cytokine storm". It can lead to acute respiratory distress syndrome (ARDS) in critical patients. Severe and critical COVID-19 cases demand oxygen therapy and mechanical ventilator support. Various drugs, including immunomodulatory and immunosuppressive agents (e.g., monoclonal antibodies (mAbs) and interleukin antagonists) have been utilized in clinical trials. However, the studies and clinical trials have documented diverging findings, which seem to be due to the differences in these drugs' possible mechanisms of action. These drugs' mechanism of action generally includes suppressing or modulating the immune system, preventing the development of cytokine storm via various signaling pathways, and enhancing the blood vessels' diameter in the lungs. In this review article, multiple medications from different drug families are discussed, and their possible mechanisms of action are also described.

Bacterial-Based Methods for Cancer Treatment: What We Know and Where We Are.

A severe disease, cancer is caused by the exponential and uncontrolled growth of cells, leading to organ dysfunction as well as disorders. This disease has been recognized as one of the significant challenges to health and medicine. Various treatment procedures for cancer are associated with diverse side effects; the most conventional cancer treatments include chemotherapy, surgery, and radiotherapy, among others. Numerous adverse and side effects, low specificity and sensitivity, narrow therapeutic windows, and, recently, the emergence of tumor cells resistant to such treatments have been documented as the shortcomings of conventional treatment strategies. As a group of prokaryotic microorganisms, bacteria have great potential for use in cancer therapy. Currently, utilizing bacteria for cancer treatment has attracted the attention of scientists. The high potential of bacteria to become non-pathogenic by genetic manipulation, their distinguished virulence factors (which can be used as weapons against tumors), their ability to proliferate in tissues, and the contingency to control their population by administrating antibiotics, etc., have made bacteria viable candidates and live micro-medication for cancer therapies. However, the possible cytotoxicity impacts of bacteria, their inability to entirely lyse cancerous cells, as well as the probability of mutations in their genomes are among the significant challenges of bacteria-based methods for cancer treatment. In this article, various available data on bacterial therapeutics, along with their pros and cons, are discussed.

Liposomal Nanomedicine: Applications for Drug Delivery in Cancer Therapy.

The increasing prevalence of cancer, a disease in which rapid and uncontrollable cell growth causes complication and tissue dysfunction, is one of the serious and tense concerns of scientists and physicians. Nowadays, cancer diagnosis and especially its effective treatment have been considered as one of the biggest challenges in health and medicine in the last century. Despite significant advances in drug discovery and delivery, their many adverse effects and inadequate specificity and sensitivity, which usually cause damage to healthy tissues and organs, have been great barriers in using them. Limitation in the duration and amount of these therapeutic agents' administration is also challenging. On the other hand, the incidence of tumor cells that are resistant to typical methods of cancer treatment, such as chemotherapy and radiotherapy, highlights the intense need for innovation, improvement, and development in antitumor drug properties. Liposomes have been suggested as a suitable candidate for drug delivery and cancer treatment in nanomedicine due to their ability to store drugs with different physical and chemical characteristics. Moreover, the high flexibility and potential of liposome structure for chemical modification by conjugating various polymers, ligands, and molecules is a significant pro for liposomes not only to enhance their pharmacological merits but also to improve the effectiveness of anticancer drugs. Liposomes can increase the sensitivity, specificity, and durability of these anti-malignant cell agents in the body and provide remarkable benefits to be applied in nanomedicines. We reviewed the discovery and development of liposomes focusing on their clinical applications to treat diverse sorts of cancers and diseases. How the properties of liposomal drugs can be improved and their opportunity and challenges for cancer therapy were also considered and discussed.