Therapeutic and preventive potential of probiotics against COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first detected in Wuhan, China and has since spread across continents. Although the globe grapples with the COVID-19 pandemic, neither a vaccine nor a drug has been proven to be effective for prevention and treatment of the disease. With millions of individuals are at high risk of contracting the disease, there is undoubtedly a need for finding a solution to control the spread of SARS-CoV-2 (1). Probiotics are living microorganisms, which exert health-beneficial attributes when consumed in sufficient amounts (2). Based on mechanism of immune regulation, probiotics can be categorized into two distinct groups, namely immunostimulatory and immunoregulatory probiotics. The former induces production of Interleukin-12 (IL-12), which stimulates interferon gamma (IFN-γ) in natural killer cells and promotes the development of T helper 1 (Th1) responses, whereas the latter is able to suppress pro-inflammatory responses through induction of IL-10 production and activation of regulatory T cells (Tregs) (3). Some probiotics can also enhance production of secretory Immunoglobulin A (sIgA) in lung tissues (4). Furthermore, probiotics are capable of interacting with intruding pathogens in several ways. For instance, they can bind to viral particles or saturate their host receptors, resulting in blockade of viral attachment (4). The genera Lactobacillus and Bifidobacterium are among the most frequently used probiotics in the management of various gastrointestinal disorders. For example, supernatants of Lactobacillus plantarum Probio-38 and Lactobacillus salivarius Probio-37 have been observed to impede in vitro infectivity of transmissible gastroenteritis virus (5), a coronavirus infecting enteric and respiratory tissues of newborn piglets with a mortality rate of almost 100%. This finding suggests that probiotics can ameliorate the severity of gastrointestinal symptoms caused by coronaviruses. Accumulating evidence also abounds on the prophylaxis and therapeutic effects of probiotics against respiratory tract viral infections (RTVIs). In this respect, pre-treatment of human laryngeal epithelial cell line HEp-2 and mouse lung epithelial cell line MLE12 with Lactobacillus gasseri SBT2055 (LG2055) suspension significantly protected the cells from respiratory syncytial virus (RSV) infection (6). In BALB/cCrSlc mice, daily oral administration of LG2055 for 21 days resulted in a perceptible decrement of RSV titers and pro-inflammatory cytokine production as well as up-regulating gene expression of type I and type II interferon in lung tissues (6). Figure 1: Possible anti-viral properties of probiotics against SARS-CoV-2 infection   In a randomized, double-blind, placebo-controlled trial, preterm infants receiving oral probiotics (Lactobacillus rhamnosus GG, ATCC 53103) exhibited a substantially lower incidence of RTVIs compared to those receiving placebo (7). One study showed that oral administration of L. rhamnosus GG is useful for achieving a reduction of antibiotics prescribed for hospitalized patients with ventilator-associated pneumonia (VAP) (2). In consistent with these findings, another randomized controlled multicenter trial demonstrated that consumption of Bacillus subtilis and Enterococcus faecalis prevents VAP as well as gastric colonization of potentially pathogenic microorganisms in critically ill patients (8). A pilot study demonstrated that nasal spray administration of Streptococcus salivarius 24SMBc for 3 days was well tolerated by all 20 healthy adult volunteers, of whom 95% were colonized by the probiotic in rhinopharynx tissues at least in the first 4 h after administration (9). According to these results, colonization of upper respiratory tract with probiotics may confer protection from viruses causing pulmonary infections, in particular rhinovirus, coronavirus, influenza virus, and RSV. Based on above-mentioned studies, we hypothesize that oral administration or even inhalation of aerosolized probiotics employing various formulations (in the form of live or heat-inactivated microorganisms) not only acts as prophylaxis, but also has the potential for adjunct therapy against SARS-CoV-2 infection. Possible beneficial roles of probiotics in COVID-19 therapy are depicted in Fig. 1. Nevertheless, clinical trials are needed to evaluate anti-viral effects of specific probiotic strains for treatment of SARS-CoV-2 infection. &nbsp

Quercetin A potential treatment for keloids

Letter to the Edito

Therapeutic Potentiality of Coenzyme Q10 for COVID-19

As coronavirus disease 2019 (COVID-19) death toll continues to surge around the globe, researchers are trying to reposition already-approved drugs for battling against sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diet and nutritional status have long been acknowledged to be associated with certain diseases. Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble, vitamin-like substance which plays a pivotal role in mitochondrial bioenergy transfer. Furthermore, it is an anti-oxidant with superb free radical-scavenging activities (1). Emerging evidence also hints that CoQ10 possesses immunomodulatory and anti-inflammatory properties. Regarding the latter, CoQ10 has been observed to inhibit expression of nuclear factor-κB, interleukin-6 (IL-6), and tumour necrosis factor-α (2). In light of the foregoing, CoQ10 has been assessed in numerous studies for its potential in treating various health conditions and maladies such as neurodegenerative disorders, cardiovascular diseases, cancers, periodontitis, diabetes, renal failure, and acquired immunodeficiency syndrome, to cite just a few (1). There have been some attempts to assess potential associations between CoQ10 levels and symptom severity in patients who suffered from pulmonary infections (2-4). In a clinical trial, elderly hospitalized patients with community-acquired pneumonia who received oral CoQ10 (200 mg/d) as an adjunct to ceftriaxone plus azithromycin for 14 days exhibited improvement with defervescence and shorter length of hospital stay as compared to the placebo group (2). Likewise, another study revealed a significant correlation between serum levels of CoQ10 and chest radiographic findings of children with pneumonia caused by H1N1 influenza (3). The same authors also demonstrated that CoQ10 levels were remarkably lower in a pediatric population infected with H1N1 influenza in comparison to both controls and seasonal influenza patients (3). This finding was further substantiated by another investigation in which patients with acute influenza showed significantly lower levels of serum CoQ10 in comparison to healthy controls (P = 0.004), suggesting that diminished levels of CoQ10 may predispose individuals for acquiring viral respiratory diseases (4). Serum levels of CoQ10 in influenza patients were also inversely correlated with certain inflammatory markers (4). Interestingly, one study has reported the beneficial effects of CoQ10 supplementation (100 mg/d for 4 weeks) in asthma patients, which was evident by a significant enhancement in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio (5). Furthermore, different nanosuspensions of CoQ10 for nebulization have been recently developed for pulmonary disorders (6), providing more effective drug medication delivery. A recent study on rats revealed that CoQ10 protects sepsis-induced acute lung injury (7). Of note, the levels of high-mobility group box 1, IL-6, macrophage inflammatory protein 2, and keratinocyte chemoattractant were significantly diminished in CoQ10 group compared with the untreated controls (P < 0.05). Similarly, administration of CoQ10 was shown to ameliorate lung and liver fibrosis in rats through modulation of autophagy in methotrexate treated rats (8). Patients suffered from COVID-19 have augmented levels of pro-inflammatory cytokines, increased risk of pneumonia, and acute respiratory distress syndrome. Owing to obvious anti-inflammatory and immunomodulatory properties of CoQ10, we envisage that the nutrient has the potential for adjuvant therapy against SARS-CoV-2 infection. On the other hand, there will be remarkable fibrotic consequences following the infection in some patients (9). Anti-fibrotic properties of CoQ10 may have a preventive role against pulmonary fibrosis secondary to COVID-19. Future clinical trials should scrutinize the therapeutic benefits of CoQ10 (in an inhaled form or oral administration) in critically ill patients. &nbsp

Investigation of blaIMP-1, blaVIM-1, blaOXA-48 and blaNDM-1 carbapenemase encoding genes among MBL-producing Pseudomonas aeruginosa

Pseudomonas aeruginosa (P. aeruginosa) places among major opportunistic nosocomial pathogen which has developed extensive drug resistance. Due to uncontrolled consumption of antibiotics, multidrug-resistant (MDR) P. aeruginosa species are increasingly isolated from various settings of hospitals globally. This research aimed to determine the genes reproducing blaOXA-48, blaIMP-1, blaVIM-1 and blaNDM-1 metallo beta lactamase (MBL) genes from MDR P. aeruginosa isolates. Herein, the isolates of 200 P. aeruginosa have been obtained from microbiology laboratory of burn ward. The antibiotic susceptibility profile was using Disc Diffusion Method (DDM and in compliance with CLSI (Clinical and Laboratory Standards Institute) advice. Study of MBL-bearing strains and the existence of encoding genes was specified by means of polymerase chain reaction. In addition, pulsed field gel electrophoresis (PFGE) is performed for typing. In this study, 124 (62%) were extended spectrum β-lactamase producer and 51 (25.5%) were MBL producers. Moreover, 148 (74%) isolates were MDR-P. aeruginosa. Additionally, 42 (21%), 21 (10%), 10 (5%) and 2 (1%) isolates carried the blaIMP-1, blaOXA-48, blaVIM-1 and blaNDM-1 genes, respectively. The PFGE showed no genetic relationships among isolates. The study observed high rate of MDR P. aeruginosa in hospital settings, though not being outbreak, which nearly half of them carried carbapenemase enzymes. Therefore, the proper control of related infections and appropriate prescription and consumption of antibiotics is essential

Antifungal effects of Zataria multiflora Boisss (Shirazi Thyme) extract against Aspergillus fumigatus Afs35 genes: crza and rpda

Aspergillus fumigatus causes a fatal infection particularly among immunocompromised individuals. Nowadays herbal and medicinal essential oils play a vital role as an alternative safe medication. Zataria multiflora Boiss essential oils have antifungal activities mainly on the expression of some gene required for fungal survival. The main objective of the study was evaluation of antifungal effects of Z. multiflora Boiss extract against A. fumigatus AfS35 strain. The strain was obtained from department of biology, Baghdad University. Various concentrations (10-300mg/mL) of Z. multiflora Boiss extract were prepared and the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined using micro-broth dilution method. The expression of crzA and rpdA genes was evaluated using the quantitative real-time PCR (RT-qPCR) technique. The concentrations ≥100mg/mL of extract inhibited the fungal growth which was non-toxic to normal cell line (MIC=100mg/mL and MFC=150mg/mL). The combination of 50mg/mL of extract plus each of amphotericin B (10mg/ml) and nystatin (10mg/mL) significantly decreased the MIC level (p<0.001). The concentration of 10mg/mL of the extract decreased the expression of crzA and rpdA genes 2.4 (p<0.001) and 3.6 (p<0.0001) fold, respectively. The same concentration of amphotericin B non- significantly decreased the crzA and rpdA genes expression by 0.6 (p=0.224) and 1.1 (p=0.033) fold, respectively. The study concluded that Z. multiflora Boiss extract exerted antifungal effect against A. fumigatus by inhibiting the cell wall biosynthesis (down-regulation of crzA), sustainability and virulence expression (rpdA). The combination therapy with Z. multifora Boiss is promising to eradicate A. fumigatus infections.

Emerging and Novel Therapies for Keloids: A compendious review

Keloids are abnormal fibroproliferative scars with aggressive dermal growth expanding beyond the borders of the original injury. Different therapeutic modalities, such as corticosteroids, surgical excision, topical silicone gel sheeting, laser therapy, cryotherapy, photodynamic therapy and radiotherapy, have been used to treat keloids; however, none of these modalities has proven completely effective. Recently, researchers have devised several promising anti-keloid therapies including anti-hypertensive pharmaceuticals, calcineurin inhibitors, electrical stimulation, mesenchymal stem cell therapy, microneedle physical contact and ribonucleic acid-based therapies. The present review summarises emerging and novel treatments for keloids. PubMed® (National Library of Medicine, Bethesda, Maryland, USA), EMBASE (Elsevier, Amsterdam, Netherlands) and Web of Science (Clarivate Analytics, Philadelphia, Pennsylvania, USA) were searched for relevant literature published between January 1987 to June 2020. A total of 118 articles were included in this review. A deeper understanding of the molecular mechanisms underlying keloid scarring pathogenesis would open further avenues for developing innovative treatments.   KEYWORDS Keloid; Treatment; Fibroblast; Scar; Dermatology

Evaluation of Fibroblast Viability Seeded on Acellular Human Amniotic Membrane

Background. Investigating the viability and proliferative rates of fibroblast cells on human amniotic membrane (HAM) as a scaffold will be an important subject for further research. The aim of this study was to assess the fibroblast viability seeded on acellular HAM, since foreskin neonatal allogenic fibroblasts seeded on HAM accelerate the wound healing process. Methods. Fibroblasts were retrieved from the foreskin of a genetically healthy male infant, and we exploited AM of healthy term neonates to prepare the amniotic scaffold for fibroblast transfer. After cell culture, preparation of acellular HAM, and seeding of cells on HAM based on the protocol, different methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 4′,6-Diamidino-2-phenylindole dihydrochloride (DAPI), and propidium iodide (PI) staining were employed for assessment of fibroblast viability on HAM. Results. Based on the results obtained from the DAPI and PI staining, the percentage of viable cells in the former staining was clearly higher than that of the dead cells in the latter one. The results of DAPI and PI staining were in accordance with the findings of MTT assay, confirming that fibroblasts were viable and even proliferate on HAM. Conclusion. Our findings showed the viability of fibroblasts seeded on the acellular HAM using MTT assay, DAPI, and PI staining; however, this study had some limitations. It would be an interesting subject for future research to compare the viability and proliferation rate of fibroblasts seeded on both cellular and acellular HAM

The Role of Probiotics in Parkinson\'s Disease: A Review Study

An upward trend in the incidence of Parkinson’s disease (PD), known as one of the most prominent neurodegenerative maladies, has evoked great concerns among medical community over the past decades. Recently, studies have suggested the initiation of PD in the gastrointestinal tract decades before the advent of manifestations. Accumulating evidence suggests that intracellular deposition of α-synuclein (α-syn) in patients with PD is associated with systemic inflammation leading to the neuroinflammation and neuropsychiatric disorders. The α-syn protein accumulation can be initiated from GI cells and distribute into CNS cells through trans-synaptic cell to cell transmission. Without doubt, gut microbiota affects the enteric nervous system (ENS) known as the “second brain”. Patients with PD have a different balance of bacteria in their intestines, as compared to healthy population. Metabolites from gut microbiota affect the enteric wall such as neurodegeneration. Probiotics have a substantial role in the neutralization or inhibition of reactive oxygen species (ROS) and free radicals and thus improve the PD symptoms. The anti-inflammatory role of probiotics also inhibits the neurodegeneration and PD development. Hence, probiotics contribute to the improvement of PD through several mechanisms which need more in-depth verification

The Association of cagA, vacA, babA2, babB and oipA of Helicobacter pylori with Risk of Gastric Carcinoma Development

Background & Objective: Helicobacter pylori (H. pylori), carried by more than half of the world population, is a major cause of chronic duodenal and gastric ulcers, gastritis and carcinoma. Colonization and toxin production include major virulence traits of H. pylori. The aim of this study was to assess the existence of H. pylori and virulence factors among patients with risk of gastrointestinal carcinoma (GC) in an Iraqi population. Materials & Methods: During May 2016- October 2020 in Babylon, Iraq, a total of 500 biopsy samples were obtained from gastric tissue of patients with GC, gastritis, duodenitis, duodenal ulcer and gastric ulcer and cultured onto the Brucella agar. H. pylori isolates were identified using conventional biochemical and molecular tests. Molecular identification was conducted by amplification of glmM gene using the polymerase chain reaction (PCR) technique. The adhesin (babA2, babB and oipA) and toxin (cagA and vacA) genes were also amplified using PCR technique. Results: Among 500 biopsy samples, 269 (110 from males and 159 from female patients) H. pylori isolates were identified. The age range of patients was 14-69 years (mean age=47.34±7.23). The babA2 and babB genes were detected in 59.47% and 59.10% of isolates, respectively. Notably, babA2 was observed in 89% of GC and 64% of DN strains being significantly more associated with GC and DN (<0.0001 and 0.028, respectively). Furthermore, babB-positive strains were significantly (0.042) more associated with PG. The rate of cagA and vacA was 44.60% and 48.32%, respectively. The cagA was detected in 64.73% of GC, and 100% of PG and DN strains with a significant association. We detected the oipA in 58.36% of strains which was significantly associated with GC (74%, P=0.0001), PG (88%, p<0.0001) and DN (84%, p<0.0001) as compared to oipA-negative strains. Conclusion: The existence of H. pylori babA2, cagA and oipA virulence genes was associated with GC, DN and PG. As these genes play a crucial role in the development of gastric carcinoma, accurate control measure toward hindering the colonization of pathogenic strains is essential

The Study of Antimicrobial Resistance among Salmonella enterica Strains Isolated from Children with Gastroenteritisin in Tehran, Iran

Background:     Salmonella enterica is one of the predominant causes of the food-borne salmonellosis in humans. The aim of this study was to determine antimicrobial resistance patterns of Salmonella enterica isolated from stool samples of children with gastroenteritisin in Tehran, Iran. Methods:     Stool samples of patients with diarrhea in a pediatric hospital in were collected from June 2017 to May 2018. Microbiological methods were used for identification of Salmonella. The identity of Salmonella enterica serotype enteritidis (S. enteritidis) was also confirmed by a multiplex-PCR. Antibiotic susceptibility testing was performed according to the standard procedure of the Clinical and Laboratory Standards Institute (CLSI). Results:     Of 800 samples, 24 were identified as Salmonella. The most prevalent serotype was S. enteritidis (n=10, 41.7%), followed by S. paratyphi C, (n=6, 25%), S. paratyphi B (n=4, 16.7%), S. arizonae 2 (n=2, 8.3%), and S. paratyphi A (n=2, 8.3%). The highest rates of antibiotic resistance were obtained for nitrofurantoin (100%), followed by nalidixic acid (45.8%), and tetracycline (16.7%). Of 24 S. enteritidis, 9 distinct antibiotypes (Abs) were observed. In this respect, 3 isolates (12.5%) were resistant to at least three or more antibiotics. The most prevalent antibiotype was AB1 (n=8, 33%), which was indicative of resistance to nitrofurantoin. Conclusion:     Considering the constant changes in antibiotic resistance patterns among food-borne pathogens over time, continuous monitoring of multidrug-resistant Salmonella isolates would definitely improve infection control strategies