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

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

Occupational leptospirosis as an underreported disease in high-risk groups: implications for prevention and control measures

Leptospirosis is a neglected zoonotic disease with no particular or verified symptoms, which has been underreported as an occupational infection.Leptospirainterrogans serovar Icterohaemorrhagiae andL. interrogansserovarGrippotyphosaare the two major pathogenic serovars. Professionals who are in constant contact with animals and their residues, in water supply, rice mill, slaughtering houses, hospital sanitary places, strawberry picking, construction works, agriculture working, forest working and food industry are at highest risk. Factors related to occupational, environmental, and recreational aspects and the presence of wild reservoirs of leptospirosis will be discussed in this concise review. Noticeably, lack of early identification, international travelling, skin wounds, sanitary and washing habitations after contact with animals, delay in treatment, and unhealthy behaviors of adolescents contribute to the disease. Hence, public education for people's awareness is essential. For instance, farmers, students, forest keepers, veterinary surgeons or veterinarians, and abattoir workers should take care by wearing cloth, such as long trousers and a long-sleeved shirt, and simple gloves to hinder the infection acquisition through skin. For people engaged in water sports, covering skin abrasions with waterproof dressings and wearing protective clothing can prevent disease transmission. However, there is no same control strategy applicable to all epidemiological wards universally. Furthermore, ecoepidemiological and cultural characteristics should be well recognized. Copyright (C) 2020 Wolters Kluwer Health, Inc. All rights reserved. Keywords:leptospirosis; occupational diseases; risk factors; zoonose