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A new next-generation probiotic, Christensenella minuta was first discovered in 2012 from healthy human stool and described under the phylum Firmicutes. C. minuta is a subdominant commensal bacterium with highly heritable properties that exhibits mutual interactions with other heritable microbiomes, and its relative abundance is positively correlated with the lean host phenotype associated with a low BMI index. It has been the subject of numerous studies, owing to its potential health benefits. This article reviews the evidence from various studies of C. minuta interventions using animal models for managing metabolic diseases, such as obesity, inflammatory bowel disease, and type 2 diabetes, characterized by gut microbiota dysbiosis and disruption of host metabolism. Notably, more studies have presented the complex interaction between C. minuta and host metabolism when it comes to metabolic health. Therefore, C. minuta could be a potential candidate for innovative microbiome-based biotherapy via fecal microbiota transplantation or oral administration. However, the detailed underlying mechanism of action requires further investigation.

Abstract Background Colon cancer is the third most commonly diagnosed cancer worldwide, with a commensurately high mortality rate. The search for novel antioxidants and specific anticancer agents which may inhibit, delay or reverse the development of colon cancer is thus an area of great interest; Streptomyces bacteria have been demonstrated to be a source of such agents. Results The extract from Streptomyces sp. MUM265— a strain which was isolated and identified from Kuala Selangor mangrove forest, Selangor, Malaysia— was analyzed and found to exhibit antioxidant properties as demonstrated via metal-chelating ability as well as superoxide anion, DPPH and ABTS radical scavenging activities. This study also showed that MUM265 extract demonstrated cytotoxicity against colon cancer cells as evidenced by the reduced cell viability of Caco-2 cell line. Treatment with MUM265 extract induced depolarization of mitochondrial membrane potential and accumulation of subG1 cells in cell cycle analysis, suggesting that MUM265 exerted apoptosis-inducing effects on Caco-2 cells. Conclusion These findings indicate that mangrove derived Streptomyces sp. MUM265 represents a valuable bioresource of bioactive compounds for the future development of chemopreventive agents, with particular promise suggested for treatment of colon cancer.

Evidence has shown that gut microbiome plays a role in modulating the development of diseases beyond the gastrointestinal tract, including skin disorders such as psoriasis. The gut–skin axis refers to the bidirectional relationship between the gut microbiome and skin health. This is regulated through several mechanisms such as inflammatory mediators and the immune system. Dysregulation of microbiota has been seen in numerous inflammatory skin conditions such as atopic dermatitis, rosacea, and psoriasis. Understanding how gut microbiome are involved in regulating skin health may lead to development of novel therapies for these skin disorders through microbiome modulation, in particularly psoriasis. In this review, we will compare the microbiota between psoriasis patients and healthy control, explain the concept of gut–skin axis and the effects of gut dysbiosis on skin physiology. We will also review the current evidence on modulating gut microbiome using probiotics in psoriasis.

There is growing evidence of studies associating COVID-19 survivors with increased mental health consequences. Mental health implications related to a COVID-19 infection include both acute and long-term consequences. Here we discuss COVID-19-associated psychiatric sequelae, particularly anxiety, depression, and post-traumatic stress disorder (PTSD), drawing parallels to past coronavirus outbreaks. A literature search was completed across three databases, using keywords to search for relevant articles. The cause may directly correlate to the infection through both direct and indirect mechanisms, but the underlying etiology appears more complex and multifactorial, involving environmental, psychological, and biological factors. Although most risk factors and prevalence rates vary across various studies, being of the female gender and having a history of psychiatric disorders seem consistent. Several studies will be presented, demonstrating COVID-19 survivors presenting higher rates of mental health consequences than the general population. The possible mechanisms by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the brain, affecting the central nervous system (CNS) and causing these psychiatric sequelae, will be discussed, particularly concerning the SARS-CoV-2 entry via the angiotensin-converting enzyme 2 (ACE-2) receptors and the implications of the immune inflammatory signaling on neuropsychiatric disorders. Some possible therapeutic options will also be considered.

Epinecidin-1 is an antimicrobial peptide derived from the orange-spotted grouper (Epinephelus coioides). The mature epinecidin-1 peptide is predicted to have an amphipathic α-helical structure and a non-helical hydrophilic domain at the C-terminal RRRH. The majority of work studying the potential pharmacological activities of epinecidin-1, utilize synthesized epinecidin-1 (Epi-1), which is made up of 21 amino acids, from the amino acid sequence of 22–42 residues of Epi-1—GFIFHIIKGLFHAGKMIHGLV. The synthetized Epi-1 peptide has been demonstrated to possess diverse pharmacological activities, including antimicrobial, immunomodulatory, anticancer, and wound healing properties. It has also been utilized in different clinical and agricultural fields, including topical applications in wound healing therapy as well as the enhancement of fish immunity in aquaculture. Hence, the present work aims to consolidate the current knowledge and findings on the characteristics and pharmacological properties of epinecidin-1 and its potential applications.

Abstract Microbial natural products serve as a good source for antioxidants. The mangrove‐derived Streptomyces bacteria have been evidenced to produce antioxidative compounds. This study reports the isolation of Streptomyces sp. MUM273b from mangrove soil that may serve as a promising source of antioxidants and UV‐protective agents. Identification and characterization methods determine that strain MUM273b belongs to the genus Streptomyces. The MUM273b extract exhibits antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging activities and also metal‐chelating activity. The MUM273b extract was also shown to inhibit the production of malondialdehyde in metal‐induced lipid peroxidation. Strong correlation between the antioxidant activities and the total phenolic content of MUM273b extract was shown. In addition, MUM273b extract exhibited cytoprotective effect on the UVB‐induced cell death in HaCaT keratinocytes. Gas chromatography–mass spectrometry analysis detected phenolics, pyrrole, pyrazine, ester, and cyclic dipeptides in MUM273b extract. In summary, Streptomyces MUM273b extract portrays an exciting avenue for future antioxidative drugs and cosmeceuticals development.

Nephrotic syndrome affects both children and adults. Idiopathic nephrotic syndrome is reported to be one of the most frequent renal pathologies in childhood. Nephrotic children are at high risk for severe pneumococcal infections as one of the life-threatening complications of nephrotic syndrome due to involvement of the immunosuppressive regimen and the acquired immune deficiency induced by nephrotic syndrome including decreased plasma IgG and low complement system components. Aiming to prevent pneumococcal infection is of paramount importance especially in this era of ever-increasing pneumococcal resistance to penicillins and cephalosporins. The pneumococcal vaccines currently available are inactivated vaccines—the two main forms in use are polysaccharide vaccines and conjugated vaccines. However, the data supporting the use of these vaccines and to guide the timing and dosage recommendations is still limited for nephrotic children. Thus, this review discusses the evidences of immunogenicity and safety profile of both vaccinations on nephrotic patients as well as the effect of nephrotic syndrome treatment on vaccine seroresponses.

Cancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is major concern. Natural products have the potential to yield unique molecules and combinations of substances that may be effective against cancer with relatively low toxicity/better side effect profile compared to standard anticancer therapy. Drug discovery work with natural products has demonstrated that natural compounds display a wide range of biological activities correlating to anticancer effects. In this review, we discuss formononetin (C16H12O4), which originates mainly from red clovers and the Chinese herb Astragalus membranaceus. The compound comes from a class of 7-hydroisoflavones with a substitution of methoxy group at position 4. Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins) and cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1), suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway], and inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins]. Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effect. Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.

Actinobacteria constitute prolific sources of novel and vital bioactive metabolites for pharmaceutical utilization. In recent years, research has focused on exploring actinobacteria that thrive in extreme conditions to unearth their beneficial bioactive compounds for natural product drug discovery. Natural products have a significant role in resolving public health issues such as antibiotic resistance and cancer. The breakthrough of new technologies has overcome the difficulties in sampling and culturing extremophiles, leading to the outpouring of more studies on actinobacteria from extreme environments. This review focuses on the diversity and bioactive potentials/medically relevant biomolecules of extremophilic actinobacteria found from various unique and extreme niches. Actinobacteria possess an excellent capability to produce various enzymes and secondary metabolites to combat harsh conditions. In particular, a few strains have displayed substantial antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), shedding light on the development of MRSA-sensitive antibiotics. Several strains exhibited other prominent bioactivities such as antifungal, anti-HIV, anticancer, and anti-inflammation. By providing an overview of the recently found extremophilic actinobacteria and their important metabolites, we hope to enhance the understanding of their potential for the medical world.

Bacterial vaginosis (BV) has been reported in one-third of women worldwide at different life stages, due to the complex balance in the ecology of the vaginal microbiota. It is a common cause of abnormal vaginal discharge and is associated with other health issues. Since the first description of anaerobic microbes associated with BV like Gardnerella vaginalis in the 1950s, researchers have stepped up the game by incorporating advanced molecular tools to monitor and evaluate the extent of dysbiosis within the vaginal microbiome, particularly on how specific microbial population changes compared to a healthy state. Moreover, treatment failure and BV recurrence rate remain high despite the standard antibiotic treatment. Consequently, researchers have been probing into alternative or adjunct treatments, including probiotics or even vaginal microbiota transplants, to ensure successful treatment outcomes and reduce the colonization by pathogenic microbes of the female reproductive tract. The current review summarizes the latest findings in probiotics use for BV and explores the potential of vaginal microbiota transplants in restoring vaginal health.

Since the 1950s, antibiotics have been used in the field of animal husbandry for growth promotion, therapy and disease prophylaxis. It is estimated that up to 80% of the antibiotics produced by the pharmaceutical industries are used in food production. Most of the antibiotics are used as feed additives at sub-therapeutic levels to promote growth. However, studies show the indiscriminate use of antibiotics has led to the emergence of multidrug-resistant pathogens that threaten both animal health and human health, including vancomycin-resistant Enterococcus (VRE), Methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae (CRE). This scenario is further complicated by the slow progress in achieving scientific breakthroughs in uncovering novel antibiotics following the 1960s. Most of the pharmaceutical industries have long diverted research funds away from the field of antibiotic discovery to more lucrative areas of drug development. If this situation is allowed to continue, humans will return to the pre-antibiotics era and potentially succumb to huge health and economic consequences. Fortunately, studies investigating various alternatives to antibiotics use in livestock show promising results. These alternatives include the application of bacteriophages and phage derived peptidoglycan degrading enzymes, engineered peptides, egg yolk antibodies, probiotics, prebiotics and synbiotics, as well as quorum quenching molecules. Therefore, this review aims to discuss the use of growth-promoting antibiotics and their impact on livestock and provide insights on the alternative approaches for animal husbandry.

People around the world ushered in the new year 2021 with a fear of COVID-19, as family members have lost their loved ones to the disease. Millions of people have been infected, and the livelihood of many has been jeopardized due to the pandemic. Pharmaceutical companies are racing against time to develop an effective vaccine to protect against COVID-19. Researchers have developed various types of candidate vaccines with the release of the genetic sequence of the SARS-CoV-2 virus in January. These include inactivated viral vaccines, protein subunit vaccines, mRNA vaccines, and recombinant viral vector vaccines. To date, several vaccines have been authorized for emergency use and they have been administered in countries across the globe. Meanwhile, there are also vaccine candidates in Phase III clinical trials awaiting results and approval from authorities. These candidates have shown positive results in the previous stages of the trials, whereby they could induce an immune response with minimal side effects in the participants. This review aims to discuss the different vaccine platforms and the clinical trials of the candidate vaccines.

Worldwide cancer incidence and mortality have always been a concern to the community. The cancer mortality rate has generally declined over the years; however, there is still an increased mortality rate in poorer countries that receives considerable attention from healthcare professionals. This suggested the importance of the prompt detection, effective treatment, and prevention strategies. The genus Streptomyces has been documented as a prolific producer of biologically active secondary metabolites. Streptomycetes from mangrove environments attract researchers’ attention due to their ability to synthesize diverse, interesting bioactive metabolites. The present review highlights research on mangrove-derived streptomycetes and the production of anticancer-related compounds from these microorganisms. Research studies conducted between 2008 and 2019, specifically mentioning the isolation of streptomycetes from mangrove areas and described the successful purification of compound(s) or generation of crude extracts with cytotoxic activity against human cancer cell lines, were compiled in this review. It is anticipated that there will be an increase in prospects for mangrove-derived streptomycetes as one of the natural resources for the isolation of chemotherapeutic agents.

There is an urgent need to search for new antibiotics to counter the growing number of antibiotic-resistant bacterial strains, one of which is methicillin-resistant Staphylococcus aureus (MRSA). Herein, we report a Streptomyces sp. strain MUSC 125 from mangrove soil in Malaysia which was identified using 16S rRNA phylogenetic and phenotypic analysis. The methanolic extract of strain MUSC 125 showed anti-MRSA, anti-biofilm and antioxidant activities. Strain MUSC 125 was further screened for the presence of secondary metabolite biosynthetic genes. Our results indicated that both polyketide synthase (pks) gene clusters, pksI and pksII, were detected in strain MUSC 125 by PCR amplification. In addition, gas chromatography-mass spectroscopy (GC-MS) detected the presence of different chemicals in the methanolic extract. Based on the GC-MS analysis, eight known compounds were detected suggesting their contribution towards the anti-MRSA and anti-biofilm activities observed. Overall, the study bolsters the potential of strain MUSC 125 as a promising source of anti-MRSA and antibiofilm compounds and warrants further investigation.

Methicillin-resistant Staphylococcus aureus (MRSA) pose a significant health threat as they tend to cause severe infections in vulnerable populations and are difficult to treat due to a limited range of effective antibiotics and also their ability to form biofilm. These organisms were once limited to hospital acquired infections but are now widely present in the community and even in animals. Furthermore, these organisms are constantly evolving to develop resistance to more antibiotics. This results in a need for new clinically useful antibiotics and one potential source are the Streptomyces which have already been the source of several anti-MRSA drugs including vancomycin. There remain large numbers of Streptomyces potentially undiscovered in underexplored regions such as mangrove, deserts, marine, and freshwater environments as well as endophytes. Organisms from these regions also face significant challenges to survival which often result in the production of novel bioactive compounds, several of which have already shown promise in drug development. We review the various mechanisms of antibiotic resistance in MRSA and all the known compounds isolated from Streptomyces with anti-MRSA activity with a focus on those from underexplored regions. The isolation of the full array of compounds Streptomyces are potentially capable of producing in the laboratory has proven a challenge, we also review techniques that have been used to overcome this obstacle including genetic cluster analysis. Additionally, we review the in vivo work done thus far with promising compounds of Streptomyces origin as well as the animal models that could be used for this work.

There are various studies that have addressed the use of Cyclosporine among patients with acute myocardial infarction (AMI). However, to date there is hardly any concise and systematically structured evidence that debate on the efficacy and safety of Cyclosporine in AMI patients. The aim of this review is to systematically summarize the overall evidence from published trials, and to conduct a meta-analysis in order to determine the efficacy and safety of Cyclosporine vs. placebo or control among patients with AMI. All randomized control trial (RCT) published in English language from January 2000 to August 2017 were included for the systematic review and meta-analysis. A total of six RCTs met the inclusion and were hence included in the systematic review and meta-analysis. Based on the performed meta-analysis, no significant difference was found between Cyclosporine and placebo in terms of left ventricular ejection fraction (LVEF) improvement (mean difference 1.88; 95% CI −0.99 to 4.74; P = 0.2), mortality rate (OR 1.01; 95% Cl 0.60 to 1.67, P = 0.98) and recurrent MI occurrence (OR 0.65; 95% Cl 0.29 to 1.45, P = 0.29), with no evidence of heterogeneity, when given to patients with AMI. Cyclosporine also did not significantly lessen the rate of rehospitalisation in AMI patients when compared to placebo (OR 0.91; 95% Cl 0.58 to 1.42, P = 0.68), with moderate heterogeneity (I2 = 46%). There was also no significant improvement in heart failure events between Cyclosporine and placebo in AMI patients (OR 0.63; 95% Cl 0.31 to 1.29, P = 0.21; I2 = 80%). No serious adverse events were reported in Cyclosporine group across all studies suggesting that Cyclosporine is well tolerated when given to patients with AMI. The use of Cyclosporine in this group of patients, however, did not result in better clinical outcomes vs. placebo at improving LVEF, mortality rate, recurrent MI, rehospitalisation and heart failure event.

Bacterial foodborne pathogens are a significant health burden and the recent emergence of pathogenic resistant strains due to the excessive use of antibiotics makes it more difficult to effectively treat infections as a result of contaminated food. Awareness of this impending health crisis has spurred the search for alternative antimicrobials with natural plant antimicrobials being among the more promising candidates as these substances have good acceptability and likely low toxicity levels as they have long been used in traditional medicines. Resveratrol (3,5,4′-trihydroxystilbene) is a naturally occurring stilbenoid which has been gaining considerable attention in medical field due to its diverse biological activities - it has been reported to exhibit antioxidant, cardioprotective, anti-diabetic, anticancer, and antiaging properties. Given that resveratrol is phytoalexin, with increased synthesis in response to infection by phytopathogens, there has been interest in exploring its antimicrobial activity. This review aims to provide an overview of the published data on the antibacterial activity of resveratrol against foodborne pathogens, its mechanisms of action as well as its possible applications in food packing and processing; in addition we also summarize the current data on its potential synergism with known antibacterials and future research and applications.

Human life expectancy is rapidly increasing with an associated increasing burden of chronic diseases, such as neurodegenerative diseases and cancer. However, there is limited progress in finding effective treatment for these conditions. For this reason, members of the genus Streptomyces have been explored extensively over the past decades as these filamentous bacteria are highly efficient in producing bioactive compounds with human health benefits. Being ubiquitous in nature, streptomycetes can be found in both terrestrial and marine environments. Previously, two Streptomyces strains (MUSC 137T and MUM 256) isolated from mangrove sediments in Peninsular Malaysia demonstrated potent antioxidant and cytotoxic activities against several human cancer cell lines on bioactivity screening. These results illustrate the importance of streptomycetes from underexplored regions aside from the terrestrial ecosystem. Here we provide the insights and significance of Streptomyces species in the search of anticancer and/or chemopreventive agents and highlight the impact of next generation sequencing on drug discovery from the Streptomyces arsenal.

Elephantopus scaber L. (family: Asteraceae) has been traditionally utilized as a folkloric medicine and scientifically shown to exhibit anti-inflammatory activities in various in vivo inflammatory models. Given the lack of study on the effect of E. scaber in neuroinflammation, this study aimed to investigate the anti-neuroinflammatory effect and the underlying mechanisms of ethyl acetate fraction from the leaves of E. scaber (ESEAF) on the release of pro-inflammatory mediators in lipopolysaccharide (LPS)-induced microglia cells (BV-2). Present findings showed that ESEAF markedly attenuated the translocation of NF-κB to nucleus concomitantly with the significant mitigation on the LPS-induced production of NO, iNOS, COX-2, PGE2, IL-1β, and TNF-α. These inflammatory responses were reduced via the inhibition of p38. Besides, ESEAF was shown to possess antioxidant activities evident by the DPPH and SOD scavenging activities. The intracellular catalase enzyme activity was enhanced by ESEAF in the LPS-stimulated BV-2 cells. Furthermore, the formation of ROS induced by LPS in BV-2 cells was reduced upon the exposure to ESEAF. Intriguingly, the reduction of ROS was found in concerted with the activation of Nrf2 and HO-1. It is conceivable that the activation promotes the scavenging power of antioxidant enzymes as well as to ameliorate the inflammatory response in LPS-stimulated BV-2 cells. Finally, the safety profile analysis through oral administration of ESEAF at 2000 mg/kg did not result in any mortalities, adverse effects nor histopathologic abnormalities of organs in mice. Taken altogether, the cumulative findings suggested that ESEAF holds the potential to develop as nutraceutical for the intervention of neuroinflammatory disorders.

Reactive oxygen species and other radicals potentially cause oxidative damage to proteins, lipids, and DNA which may ultimately lead to various complications including mutations, carcinogenesis, neurodegeneration, cardiovascular disease, aging, and inflammatory disease. Recent reports demonstrate that Streptomyces bacteria produce metabolites with potent antioxidant activity that may be developed into therapeutic drugs to combat oxidative stress. This study shows that Streptomyces sp. MUM212 which was isolated from mangrove soil in Kuala Selangor, Malaysia, could be a potential source of antioxidants. Strain MUM212 was characterized and determined as belonging to the genus Streptomyces using 16S rRNA gene phylogenetic analysis. The MUM212 extract demonstrated significant antioxidant activity through DPPH, ABTS and superoxide radical scavenging assays and also metal-chelating activity of 22.03 ± 3.01%, 61.52 ± 3.13%, 37.47 ± 1.79%, and 41.98 ± 0.73% at 4 mg/mL, respectively. Moreover, MUM212 extract was demonstrated to inhibit lipid peroxidation up to 16.72 ± 2.64% at 4 mg/mL and restore survival of Vero cells from H2O2-induced oxidative damages. The antioxidant activities from the MUM212 extract correlated well with its total phenolic contents; and this in turn was in keeping with the gas chromatography–mass spectrometry analysis which revealed the presence of phenolic compounds that could be responsible for the antioxidant properties of the extract. Other chemical constituents detected included hydrocarbons, alcohols and cyclic dipeptides which may have contributed to the overall antioxidant capacity of MUM212 extract. As a whole, strain MUM212 seems to have potential as a promising source of novel molecules for future development of antioxidative therapeutic agents against oxidative stress-related diseases.

Nerolidol (3,7,11-trimethyl-1,6,10-dodecatrien-3-ol) is a naturally occurring sesquiterpene alcohol that is present in various plants with a floral odor. It is synthesized as an intermediate in the production of (3E)-4,8-dimethy-1,3,7-nonatriene (DMNT), a herbivore-induced volatile that protects plants from herbivore damage. Chemically, nerolidol exists in two geometric isomers, a trans and a cis form. The usage of nerolidol is widespread across different industries. It has been widely used in cosmetics (e.g., shampoos and perfumes) and in non-cosmetic products (e.g., detergents and cleansers). In fact, U.S. Food and Drug Administration (FDA) has also permitted the use of nerolidol as a food flavoring agent. The fact that nerolidol is a common ingredient in many products has attracted researchers to explore more medicinal properties of nerolidol that may exert beneficial effect on human health. Therefore, the aim of this review is to compile and consolidate the data on the various pharmacological and biological activities displayed by nerolidol. Furthermore, this review also includes pharmacokinetic and toxicological studies of nerolidol. In summary, the various pharmacological and biological activities demonstrated in this review highlight the prospects of nerolidol as a promising chemical or drug candidate in the field of agriculture and medicine.

Dysbiosis is a prominent factor in numerous inflammatory conditions, with Ruminococcus gnavus, a prevalent gut microbe, implicated in inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), eczema, metabolic disorders, and rheumatic diseases. R. gnavus contributes to inflammation by producing an inflammatory polysaccharide and degrading mucin. The increasing evidence of elevated R. gnavus abundance in various inflammatory conditions suggests its potential as a therapeutic target. Despite this, there are limited studies on treatment strategies targeting R. gnavus. This article provides a comprehensive overview of the association between R. gnavus and diverse inflammatory conditions, highlighting the need for further research to explore effective treatment options against this bacterium. [ABSTRACT FROM AUTHOR]