Polymorphisms in vitamin D receptor genes and its relation with susceptibility to brucellosis: a case-control study.

OBJECTIVE: One of the systemic infections is Brucellosis which is caused by facultative intracellular bacteria of the genus Brucella. Vitamin D is a fat-soluble prohormone, that metabolizes enzymes and its intracellular receptor creates the active hormone and also mediate in responses of immune system. METHODS: Current research consists of 102 patients with brucellosis who were selected based on culture, PCR results serology, and clinical symptoms. The control group composed of 102 healthy people. The polymorphism of genes (Bsm I, Fok I, Taq I, Apa I) encoding Vitamin D receptor (VDR) were assessed by the PCR-RFLP method. RESULTS: The results showed that ff, tt, aa, and bb genotypes in Fok I, ApaI, TaqI, and BsmI were significant in case/control groups (P-value ≤ 0.0001). The genotype frequency AA in the control group is higher than that of the study group, while genotype frequency aa in the study group is more than the control. The odds ratio for brucellosis in individuals with ff genotype is 37 times higher than that of Ff genotype. Also, the odds ratio of brucellosis in individuals with genotype tt, aa, and bb was 12, 53, and 6 times higher than those of the Aa, Bb, and Tt genotypes. CONCLUSION: The genotypes aa and ff in the positions of the ApaI and FokI are of higher importance. The brucellosis risk in individuals accompanied aa genotype at Apa I is 53 times higher than that of the genotype AA, in other words, AA and BB, TT and FF genotypes are protective against the disease.

Molecular typing of multi-drug resistant Acinetobacter baumannii isolates from clinical and environmental specimens in three Iranian hospitals by pulsed field gel electrophoresis.

BACKGROUND: Multi-drug resistant (MDR) Acinetobacter baumannii is one of the most important causes of nosocomial infections. The purpose of this study was to identify antibiotic resistance patterns, biofilm formation and the clonal relationship of clinical and environmental isolates of A. baumannii by Pulsed Field Gel Electrophoresis method. Forty-three clinical and 26 environmental isolates of the MDR A. baumannii were collected and recognized via API 20NE. Antibiotic resistance of the isolates was assessed by the disk diffusion method, and the biofilm formation test was done by the microtiter plate method. Pulsed Field Gel Electrophoresis (PFGE) was used to assess the genomic features of the bacterial isolates. RESULTS: The resistance rate of clinical and environmental isolates against antibiotics were from 95 to 100%. The difference in antibiotic resistance rates between clinical and environmental isolates was not statistically significant (p > 0.05). Biofilm production capabilities revealed that 31 (44.9%), and 30 (43.5%) isolates had strong and moderate biofilm producer activity, respectively. PFGE typing exhibited eight different clusters (A, B, C, D, E, F, G, and H) with two significant clusters included A and G with 21 (30.4%) and 16 (23.2%) members respectively, which comprises up to 53.6% of all isolates. There was no relationship between biofilm formation and antibiotic resistance patterns with PFGE pulsotypes. CONCLUSIONS: The results show that there is a close relationship between environmental and clinical isolates of A. baumannii. Cross-contamination is also very important that occurs through daily clinical activities between environmental and clinical isolates. Therefore, in order to reduce the clonal contamination of MDR A. baumannii environmental and clinical isolates, it is necessary to use strict infection control strategies.

The importance of intracellular bacterial biofilm in infectious diseases.

Various bacterial species, previously known as extracellular pathogens, can reside inside different host cells by adapting to intracellular modes by forming microbial aggregates with similar characteristics to bacterial biofilms. Additionally, bacterial invasion of human cells leads to failure in antibiotic therapy, as most conventional anti-bacterial agents cannot reach intracellular biofilm in normal concentrations. Various studies have shown that bacteria such as uropathogenic Escherichia coli, Pseudomonas aeruginosa, Borrelia burgdorferi,Moraxella catarrhalis, non-typeable Haemophilus influenzae, Streptococcus pneumonia, and group A Streptococci produce biofilm-like structures within the host cells. For the first time in this review, we will describe and discuss the new information about intracellular bacterial biofilm formation and its importance in bacterial infectious diseases.

DNA-protein interaction: identification, prediction and data analysis.

Life in living organisms is dependent on specific and purposeful interaction between other molecules. Such purposeful interactions make the various processes inside the cells and the bodies of living organisms possible. DNA-protein interactions, among all the types of interactions between different molecules, are of considerable importance. Currently, with the development of numerous experimental techniques, diverse methods are convenient for recognition and investigating such interactions. While the traditional experimental techniques to identify DNA-protein complexes are time-consuming and are unsuitable for genome-scale studies, the current high throughput approaches are more efficient in determining such interaction at a large-scale, but they are clearly too costly to be practice for daily applications. Hence, according to the availability of much information related to different biological sequences and clearing different dimensions of conditions in which such interactions are formed, with the developments related to the computer, mathematics, and statistics motivate scientists to develop bioinformatics tools for prediction the interaction site(s). Until now, there has been much progress in this field. In this review, the factors and conditions governing the interaction and the laboratory techniques for examining such interactions are addressed. In addition, developed bioinformatics tools are introduced and compared for this reason and, in the end, several suggestions are offered for the promotion of such tools in prediction with much more precision.

Irrigation with Bupivacaine at the Surgical Bed for Postoperative Shoulder Tip and Abdominal Pain Relief after Laparoscopic Cholecystectomy.

Gallstones in western countries are primarily composed of cholesterol. However, mixed or pigment stones, which contain a higher proportion of bilirubin, are more frequently seen in developing nations and Asia than in western countries. Abdominal and shoulder tip pains (STPs) are common complaints following the standard laparoscopic cholecystectomy procedure. To date, all pain management modalities have proven variable outcomes. This prospective randomized study included 82 patients who underwent elective laparoscopic cholecystectomy. The control group received 20 mL of normal saline, whereas the study group received a 20-mL instillation of 0.5% bupivacaine at the gallbladder bed after surgical resection. The Visual Analog Scale (VAS) was used to analyze abdominal pain and STP. The mean age ranged from 20 to 80 years. Abdominal VAS at 6, 12, 18, 24, 30, 36, and 48 hours were statistically insignificant. The majority were discharged on postoperative day 1 (32 studies, 37 control). Follow-up VAS after 1 week for STP VAS and abdominal pain VAS in both groups were statistically insignificant. Even with small numbers of a well-conducted randomized trial, we demonstrated that bupivacaine irrigation at the gallbladder bedpost laparoscopic cholecystectomy does not affect pain relief.

Comparative de novo transcriptome analysis of flower and root of Oliveria decumbens Vent. to identify putative genes in terpenes biosynthesis pathway.

The Oliveria decumbens Vent. is a wild, rare, annual medicinal plant and endemic plant of Iran that has metabolites (mostly terpenes) which make it a precious plant in Persian Traditional Medicine and also a potential chemotherapeutic agent. The lack of genetic resources has slowed the discovery of genes involved in the terpenes biosynthesis pathway. It is a wild relative of Daucus carota. In this research, we performed the transcriptomic differences between two samples, flower and root of Oliveria decumbens, and also analyze the expression value of the genes involved in terpenoid biosynthesis by RNA-seq and its essential oil's phytochemicals analyzed by GC/MS. In total, 136,031,188 reads from two samples of flower and root have been produced. The result shows that the MEP pathway is mostly active in the flower and the MVA in the root. Three genes of GPP, FPPS, and GGPP that are the precursors in the synthesis of mono, di, and triterpenes are upregulated in root and 23 key genes were identified that are involved in the biosynthesis of terpenes. Three genes had the highest upregulation in the root including, and on the other hand, another three genes had the expression only in the flower. Meanwhile, 191 and 185 upregulated genes in the flower and root of the plant, respectively, were selected for the gene ontology analysis and reconstruction of co-expression networks. The current research is the first of its kind on Oliveria decumbens transcriptome and discussed 67 genes that have been deposited into the NCBI database. Collectively, the information obtained in this study unveils the new insights into characterizing the genetic blueprint of Oliveria decumbens Vent. which paved the way for medical/plant biotechnology and the pharmaceutical industry in the future.

Potential of Bacillus subtilis Against SARS-CoV-2 - A Sustainable Drug Development Perspective.

The COVID-19 pandemic had anomalous yet inevitable impacts on the world's economies, healthcare systems, and all other aspects of life. Researchers began to uncover hidden routes to find a new horizon of hope using underrated resources. Biosurfactants are sustainable biomolecules with an active surface, unique characteristics, and extensive uses. Bacillus species showed the highest amount of biosurfactant activities and Bacillus subtilis is one of them. The antiviral, antimicrobial, and anti-inflammatory activity of B. subtilis was proven recently. The great advantage is its non-toxic nature. Pro-inflammatory cytokines including IL-1 ß, 6, 8, 12, 18, and TNF-(α are secreted in higher amounts when neutrophils and monocytes are triggered by biosurfactant bacteria. This point of view furnishes the potential application of B. subtilis and its biomolecules against COVID-19, either in the form of a vaccine/therapeutic agent, for a greener environment, healthier life, and environmental sustainability. Further in vivo and clinical trials are needed to validate this hypothesis.

Molecular Detection of blaOXA -type Carbapenemase Genes and Antimicrobial Resistance Patterns among Clinical Isolates of Acinetobacter baumannii.

Acinetobacter baumannii is a bacterium found in most places, especially in clinics and hospitals, and an important agent of nosocomial infections. The presence of class D enzymes such as OXA-type carbapenemases in A. baumannii is proven to have a key function in resistance to carbapenem. The aim of the current study is to determine the blaOXA -type carbapenemase genes and antimicrobial resistance among clinically isolated samples of A. baumannii. We assessed 100 clinically isolated specimens of A. baumannii from patients in intensive care units of educational hospitals of Hamadan, West of Iran. The A. baumannii isolates' susceptibility to antibiotics was performed employing disk diffusion method. Multiplex polymerase chain reaction was used to identify the bla OXA-24-like , bla OXA-23-like , bla OXA-58-like , and bla OXA-51-like genes. The bla OXA-23-like , bla OXA-24-like , and bla OXA-58-like genes' prevalence were found to be 84, 58, and 3%, respectively. The highest coexistence of the genes was for bla OXA-51/23 (84%) followed by bla OXA-51/24-like (58%). The bla OXA-51/23- like pattern of genes is a sort of dominant gene in resistance in A. baumannii from Hamadan hospitals. The highest resistance to piperacillin (83%) and ciprofloxacin (81%) has been observed in positive isolates of bla OXA-23-like . The A. baumannii isolates with bla OXA-58-like genes did not show much resistance to antibiotics. Based on the results of the phylogenetic tree analysis, all isolates have shown a high degree of similarity. This study showed the high frequency of OXA -type carbapenemase genes among A. baumannii isolates from Hamadan hospitals, Iran. Thus, applying an appropriate strategy to limit the spreading of these strains and also performing new treatment regimens are necessary.

Inclusion of Cephalexin in COVID-19 Treatment Combinations May Prevent Lung Involvement in Mild Infections: A Case Report with Pharmacological Genomics Perspective.

Novel coronavirus disease 2019 (COVID-19) is caused by a nonsegmented positive sense RNA, enveloped RNA virus that belongs to the family of ß-coronaviridae. This virus shall cause acute respiratory distress syndrome (ARDS) which consequently leads to breathing difficulty and need to admit to intensive care units (ICUs). The current conventional treatment combination in most of the hospitals in Iran includes azithromycin 500 + naproxen 500 + vitamin C 1,000 + Zinc + vitamin D3 1,000. In this case reports ( n = 4), we would like to report significant findings in course of COVID-19 treatment reported to our clinic on August 8 and 9, 2020; patients presented as walk in and were advised house isolation and complete bed rest as there were no signs of lung involvement and their overall condition was stable. By the inclusion of cephalexin 500 in treatment combination, patients who received cephalexin 500 for 5 days along with other medicines did not develop any lung involvement and breathing complications. Cephalexin is the gold standard in upper and lower respiratory tract infections and here also shall play a vital role besides other conventional therapies. Azithromycin is a macrodial antibiotic working via the ABCB1 gene pathway. As of date, there is no clear evidence of pharmacogenomics data in COVID-19 patients. More research needs to be performed in COVID-19 before any sort of pharmacogenomics tests could be advised.

Evaluation of the Anti-cancer Effect of Syzygium cumini Ethanolic Extract on HT-29 Colorectal Cell Line.

INTRODUCTION: GLOBOCAN 2018 data indicates the incidence and mortality of colorectal cancer that is the third lethal and fourth most diagnosed cancer in the world. There has been significant progress in cancer therapy while the ability of cancerous cells to survive is one of the main challenges in cancer research. Still, conventional therapies like surgery, chemo, and radiotherapy are widely used options. Therefore, efforts put in action by researchers in the field of drug design, molecular genetics, and biomedicine to come across safer substances with the minimum unwanted side effects to be utilized in cancer treatment. Plant-derived compounds are ideal options as they might have a better outcome with minimal side effects. METHODS: In the current research, the anti-cancer effect of Syzygium cumini ethanolic extract (SCE) was evaluated on the HT-29 colorectal cancer cell line. To this end, the apoptosis rate and proliferation of HT-29 cell lines after exposure to SCE were investigated through MTT, and other methods including DNA damage assessment and scratch test also employed to evaluate the metastasis and cell migration capacity of HT-29 after treatment with SCE. Behind that, expression ration of genes involved in the process of apoptosis has been studied, including Bax and Bcl-2 that were measured by qRT-PCR. RESULTS: Based on the MTT test, SCE suppresses the growth of HT-29 cell lines drastically. Expression analysis of the ratio of desired genes (Bax: Bcl-2) also changed significantly after treatment by SCE. DNA damage test confirmed DNA lost its integrity and gone through apoptosis, and wound healing suggests the lower change of metastasis after treatment by SCE. CONCLUSION: The outcome of this study suggests that Syzygium cumini might be contemplating as a future chemotherapeutic agent and suitable candidate for in vivo trial.

Impact of SARS-CoV-2 Genetic Blueprints on the Oral Manifestation of COVID-19: A Case Report.

Nonsegmented positive-sense RNA enveloped RNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can result in coronavirus disease 2019 (COVID-19). This virus is from ß-coronaviridae family of viruses. The common signs and symptoms of COVID-19 include pyrexia, cough, dyspnea, fatigue, myalgia, cephalgia, diarrhea, and nausea. Physicians and dentists around the world could directly link the COVID-19 and oral diseases such as ageusia and anosmia. After time passes, different aspects of symptoms of the diseases have been discovered. Research suggests that the oral cavity is the most vulnerable region for the virus because of angiotensin-converting enzyme-2 (ACE2) receptor abundance in the mouth. In this case report (no. of patients = 6), we would like to report significant findings in patients who were diagnosed with COVID-19 reported to our clinic during May 2021 complaining about the oral manifestation of it such as xerostomia, gingival inflammation, and cracked teeth. All patients are younger than 40 years with no history of dental complaints and oral diseases. Fortunately, these symptoms are not life threatening and treatable/manageable by current treatment options. To date, there is no clear proof of how and via which pathway, SARS-CoV-2 genomic blueprint causes the oral manifestation of COVID-19 beside ACE2 receptor which is the only known biopathway for such incidents.

To Study the Anti-cancer Effects of Shigella Flexneri in AspC-1 Pancreatic Cancer Cell Line in Approach to Bax and bcl-2 Genes.

INTRODUCTION: Cancer is the uncontrolled division of cells and can be caused by genetic or environmental factors. Pancreatic cancer is one of the deadliest among all cancers. The role of bacteria as an anticancer agent dates back to almost 100 years ago. The microbiome has recently become a focus of research in carcinogenesis and even pancreatic cancer. Shigella flexneri is a gram-negative bacterium, which causes shigellosis with symptoms such as diarrhea, fever, and stomach cramps in human. Shigella flexneri may play a very important role in the internal pathways of apoptosis and may induce apoptosis in some of the cancerous cells. MATERIAL AND METHODS: In this experiment bacteria were cultured on Salmonella-Shigella agar, then inoculated into BHI Broth medium. After sonication, the protein concentration of the bacterium was measured by using the ZellBio Sensitive Protein Bradford Assay kit. MTT assay was performed to obtain IC50 for the said bacterial protein. Later by cDNA kit synthesized the cDNA based on the RNA template. In the end, the results were analyzed using real-time PCR and the expression of Bax and Bcl-2 genes was measured before and after treatment. RESULTS: The results showed that Shigella flexneri has the potential anti-proliferative effect in pancreatic cancer. The inhibitory concentration, pro-apoptotic amount to upregulate Bax, and meanwhile also to downregulate the bcl-2 found to be 10 µl. CONCLUSION: In general, due to defects in the apoptotic pathway in cancer cells and the existence of drug-resistant cells, the detection of new apoptotic inducers such as Shigella flexneri cell extract can be used for further studies on cancer therapy.

Concise Update on Genomics of COVID-19: Approach to Its latest Mutations, Escalated Contagiousness, and Vaccine Resistance.

The novel coronavirus disease 2019 (COVID-19) that started to invade the world from the Chinese fish market, causes an acute respiratory distress syndrome. COVID-19 is a dreadful infectious disease that surfaced only less than 8 months ago and caused the deadly COVID-19 pandemic. In this new species with a positive, single-strand RNA genome and a huge size, from the proteomics point view, there are no changes in sequences of amino acids in NSP7, 13, matrix, or envelope or other proteins including 8b and p6 and excluding NSP2 and NSP3. P6 is a multifunctional golgi-endoplasmic reticulum membrane-associated protein. This complex has a key duty to increase the replication rate of the virus and also causes intrinsic immune system responses by suppressing the signal transducer and activator of transcription factor 1 (STAT 1) translocated to the nucleus. Palmitoylated proteins elevate hydrophobicity which helps in membrane connection. Inside the N-linked glycosylation, moieties oligosaccharide is adhering to Asn-X-Ser/Thr canonical sequence. This helps for exact enfolding and carrying viral proteins by industriously using host's chaperon proteins including calreticulin and calnexin. 2B proteins encourage the internalization of major histocompatibility complex, class-I (MHC-I) protein and meanwhile inhibit their transfer to the surface of the cell as a recognition side. The deubiquitination of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has precise modification apparatus in the posttranslational stage. In this article, we outlined the recent and up-to-date data on genomic and molecular structures, epidemiology, vaccine development, and, last but not least, the clinical features, diagnostics, and treatment of the novel coronavirus.

Potential of CRISPR/Cas13 System in Treatment and Diagnosis of COVID-19.

The novel coronavirus disease 2019 (COVID-19) belongs to coronaviridae families like sarbecovirus (SARS), and causes pyrexia, pertussis, and acute respiratory distress syndrome (ARDS) in major. Started from Wuhan, China, COVID-19 now forced the World Health Organization (WHO) call it a global pandemic. These dreadful figures elevate the need for rapid action for a rapid diagnostic tool, an efficacious therapy, or vaccine for such widespread disease. In this article, we reviewed all the latest research and trials including conventional antiviral medicines that have a narrow and finite effect on COVID-19. Recently, some advances were made by a nucleotide/nucleoside analogues (NUC) inhibitor (remdesivir), ivermectin (antiparasitic drug), and convalescent plasma; the later one has more recently been approved by the Food and Drug Administration (FDA). Additionally, a clinical-grade soluble human angiotensin-converting enzyme (ACE2), named hrsACE2, was able to inhibit the infection of human blood vessel organoids, as well as the human kidney organoids, by the virus. As of now, innovative therapeutics based on the CRISPR/Cas13d might overcome the challenge of COVID-19 either as a treatment option or precise and rapid diagnostic tool due to its rapid and precise nature. In this updated comprehensive rapid review, we tried to cover all recent findings in terms of genomics, diagnosis, prevention, and treatment.

Apoptosis Detection Methods in Diagnosis of Cancer and Their Potential Role in Treatment: Advantages and Disadvantages: a Review.

INTRODUCTION: Interruption of regulation of apoptosis can play a leading role in cancers where elevated apoptosis causes neurodegeneration, autoimmunity, AIDS, and ischemia. One famous example can be p53's downregulation, which is a tumor suppressor gene, which consequently can cause a decrease in apoptosis rate and intense tumor growth and progression and development and inactivation of 53; it can be extended to many cancers in human. Anyhow, apoptosis is a double-edge sword. There are many trials and studies are going on observation and understanding of different steps involved in apoptosis. Apoptosis has a very major role in carcinogenesis and the treatment of cancer. AIM: In this updated-cum-comprehensive review, we would like to cover what is apoptosis and cancer and also, will discuss all known methods of apoptosisdetection, their applicability in the treatment of cancer, and their advantages, disadvantages, and limitations. MATERIAL AND METHODS: Published articles on indexing sources such as PubMed, Scopus from 2000 to date. RESULT: By considering all above information including each methods pros and cons, these routine methods could be great tool with distinctive qualities in treatmentwhich can be great help from patient perspective and as well from government ad health care system point of view. CONCLUSION: Accurate diagnosis of cell apoptotic biopathways at different stages assists in evaluating near to exact apoptotic index, which is the perfect sign andindicator for metastasis and also prognosis, thus foreseeing treatment outcome.

Chromium Supplementation; Negotiation with Diabetes Mellitus, Hyperlipidemia and Depression.

Chromium (Cr) is an essential trace element which found naturally in a daily diet and available in the form of supplementary tablets to boost disorders like diabetes mellitus (DM) and functions like lipid metabolism and beneficial on depression too. Diabetes is one of the most prevalent endocrine diseases or in other words, the most severe metabolic syndrome (MS), which associated with high production of free-radicals which is out of bodies detoxifying machine capacity or high oxidative stress (HOS), vasculitis and elevated lipid profile. many research papers and clinical trials published about the significance of chromium on biological activities, pre and post clinical. For this review research articles, clinical trials, from 1st Jan'10 to 31st Dec'18 and refer literature for the biochemical, pharmacological and biological activity of Chromium. Primarily articles gathered from the above search engines. Then precisely according to our aim and goal and regarding designed objectives dismisses similar articles and finally came to 84 articles for the above said period. This review trying to cover the entire picture from what chromium is to the recent updates on their greater role in increasing insulin sensitivity of cells and enhancing lipid metabolism and even recent findings suggest its positive effects including prevention and ameliorating properties on depression. The biological activities, pharmacological features, clinical implications including efficacy and role of chromium compounds on the glycaemic index will be discussed. The outcome of this review is to bring the pros and cons of chromium supplementation along with is safety and toxicity concern beside molecular pathways, biochemistry and clinical trials, all in one comprehensive review.

Anti-Cancer Effect of Melatonin via Downregulation of Delta-like Ligand 4 in Estrogen-Responsive Breast Cancer Cells.

BACKGROUND: The Notch signaling pathway has a key role in angiogenesis and Delta - Like Ligand 4 (DLL4) is one of the main ligands of Notch involved in cell proliferation in sprouting vessels. OBJECTIVE: In this study, we aimed to evaluate the expression of DLL4 in primary breast tumors and to examine the effect of melatonin on DLL4 expression in vitro. METHODS: Eighty-five breast tumor and paired adjacent non-tumor tissue samples were collected. Apoptosis assay was performed on breast cancer cells to evaluate melatonin effects. Western blot and quantitative RT-PCR were used to measure DLL4 expression. Then, we investigated the effect of melatonin on the expression of DLL4 in four breast cancer cell lines at RNA and protein levels. We also performed a probabilistic neural network analysis to study genes closely associated with DLL4 expression. RESULTS: Our results showed a significantly higher expression of DLL4 in tumor tissues compared to non-tumor tissues (P = 0.027). Melatonin treatment substantially attenuated DLL4 expression in BT474 and MCF-7 cells, but not in SK-BR-3 and MDA-MB-231 cells. Also, melatonin induced apoptosis in all four cell lines. Network analysis revealed a set of 15 genes that had close association and interaction with DLL4. DLL4 was overexpressed in breast cancer tissues as compared to the non-tumor tissues. CONCLUSION: It can be concluded that melatonin treatment attenuated DLL4 expression only in estrogen- responsive breast cancer cells and is able to induce apoptosis in breast cancer cells.