VagiBIOM Lactobacillus suppository improves vaginal health index in perimenopausal women with bacterial vaginosis: a randomized control trial.

Bacterial vaginosis (BV) can cause vaginal dysbiosis that may influence general vaginal health and pregnancy complications. Balancing vaginal microbiome using Lactobacillus spp. may be a new way to prevent and treat mild BV. We conducted a randomized, double-blind, placebo-controlled pilot study aimed at evaluating the effect of the product VagiBIOM, a multi-Lactobacillus vaginal suppository, on peri- and premenopausal women with BV in restoring vaginal pH and overall vaginal health by resetting the vaginal microbiome composition. Sixty-six peri- and premenopausal women with BV symptoms were randomized with a 2:1 ratio to be treated with VagiBIOM or placebo suppositories. Vaginal pH, VAS itching score, total Nugent score, and vaginal health index (VHI) were measured. Vaginal microbiome changes before and after the treatment were analyzed by 16S rRNA sequencing and bioinformatics analysis. After 4 weeks of intervention with VagiBIOM or a placebo, the mean score for vaginal pH, VAS itching, and total Nugent score was significantly decreased from the baseline. Compared to the baseline scores, the VHI scores improved significantly following 28-day intervention (p < 0.001). Our results revealed two Lactobacillus species, L. hamsteri, and L. helveticus, as indicator species occurring differentially in the VagiBIOM-treated group. Furthermore, the regression and species network analyses revealed significant bacterial associations after VagiBIOM treatment. Lactobacillus hamsteri was positively associated with the Nugent score and negatively associated with vaginal pH. L. iners and L. salivarius were positively and inversely associated with VHI. As is typical, Bacteroides fragilis was positively associated with vaginal pH and negatively associated with the Nugent score. Interestingly, the Lactobacillus spp. diversity improved after VagiBIOM treatment. The VagiBIOM suppository treatment for peri- and premenopausal women with BV significantly relieved vaginal itching by decreasing vaginal pH and Nugent scores and improving the overall VHI after 4 weeks' intervention. This effect was primarily the result of VagiBIOM improving vaginal Lactobacillus diversity.Trial Registration ClinicalTrials.gov registration: NCT05060029, first registration 09/28/2021: Title: A Pilot Study to Evaluate the Efficacy and Safety of Lactobacillus Species Suppositories on Vaginal Health and pH.

Reply to Kulic, Z. Comment on "Subhadra et al. Significant Broad-Spectrum Antiviral Activity of Bi121 against Different Variants of SARS-CoV-2. Viruses 2023, 15, 1299".

We would like to thank Dr. Zarko Kulic [...].

Significant Broad-Spectrum Antiviral Activity of Bi121 against Different Variants of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has so far infected 762 million people with over 6.9 million deaths worldwide. Broad-spectrum viral inhibitors that block the initial stages of infection by reducing virus binding and proliferation, thereby reducing disease severities, are still an unmet global medical need. We studied Bi121, which is a standardized polyphenolic-rich compound isolated from Pelargonium sidoides, against recombinant vesicular stomatitis virus (rVSV)-pseudotyped SARS-CoV-2S (mutations in the spike protein) of six different variants of SARS-CoV-2. Bi121 was effective at neutralizing all six rVSV-ΔG-SARS-CoV-2S variants. The antiviral activity of Bi121 was also assessed against SARS-CoV-2 variants (USA WA1/2020, Hongkong/VM20001061/2020, B.1.167.2 (Delta), and Omicron) in Vero cells and HEK-ACE2 cell lines using RT-qPCR and plaque assays. Bi121 showed significant antiviral activity against all the four SARS-CoV-2 variants tested, suggesting a broad-spectrum activity. Bi121 fractions generated using HPLC showed antiviral activity in three fractions out of eight against SARS-CoV-2. The dominant compound identified in all three fractions using LC/MS/MS analysis was Neoilludin B. In silico structural modeling studies with Neoilludin B showed that it has a novel RNA-intercalating activity toward RNA viruses. In silico findings and the antiviral activity of this compound against several SARS-CoV-2 variants support further evaluation as a potential treatment of COVID-19.

Colorectal Cancer and Probiotics: Are Bugs Really Drugs?

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. There are many factors that predispose a patient to the disease such as age, family history, ethnicity, and lifestyle. There are different genetic factors and diseases that also increase a person's risk for developing CRC. Studies have found associations between gut microbiome and the risk for developing versus protection against CRC. Normal gut microbiome aid in daily functions of the human body such as absorption, metabolism, detoxification, and regulation of inflammation. While some species of bacteria prevent CRC development and aid in therapeutic responses to various treatment regiments, other species seem to promote CRC pathogenesis. In this regard, many studies have been conducted to not only understand the biology behind these opposing different bacterial species; but also to determine if supplementation of these tumor opposing bacterial species as probiotics lends toward decreased risk of CRC development and improved therapeutic responses in patients with CRC. In this literature review, we aim to discuss the basics on colorectal cancer (epidemiology, risk factors, targets, treatments), discuss associations between different bacterial strains and CRC, and discuss probiotics and their roles in CRC prevention and treatment.

Draft Whole-Genome Sequence of Lactobacillus fermentum LfQi6, Derived from the Human Microbiome.

We report a 2.21-Mbp draft whole-genome sequence of Lactobacillus fermentum Qi6 (LfQi6). This strain demonstrates activity against pathogenic biofilms, enhances the skin barrier, and upregulates innate immune defenses. The genome sequence information of this strain will help to identify molecules that hold promise for the discovery of novel therapeutics for dermatological disorders.

Neuroserpin up-regulation in the Alzheimer's disease brain is associated with elevated thyroid hormone receptor-ß1 and HuD expression.

Neuroserpin, the major inhibitor of tissue plasminogen activator (tPA) in brain, has been shown to be up-regulated in Alzheimer's disease (AD). Inhibition of tPA activity leads to reduced brain levels of plasmin, one of the main enzymes responsible for the degradation and clearance of amyloid-beta and its plaques from the brain. Thyroid hormone is one of the few factors known to enhance expression of neuroserpin in neurons. Thyroid hormone acts on neurons by binding to its receptors THR1α and THR1ß, which then function in the nucleus to up-regulate the expression of numerous genes including the RNA-binding protein HuD. HuD acts post-transcriptionally to enhance expression of numerous proteins including neuroserpin by stabilizing their mRNAs. A series of Alzheimer's disease brain tissues were compared to age-matched control brains for their expression of neuroserpin, THRß1 and HuD by western blotting. Alzheimer's disease brain tissues with elevated neuroserpin protein also showed increased expression of THRß1 and HuD. Pair-wise analyses showed significant correlation p-values between neuroserpin, THRß1 and HuD levels; suggesting that the up-regulation of neuroserpin in Alzheimer's disease brain may result from an activation of the thyroid hormone response system in these individuals. These findings provide evidence for a potential relationship between thyroid hormone disorders and Alzheimer's disease.

Algal biorefinery-based industry: an approach to address fuel and food insecurity for a carbon-smart world.

Food and fuel production are intricately interconnected. In a carbon-smart society, it is imperative to produce both food and fuel sustainably. Integration of the emerging biorefinery concept with other industries can bring many environmental deliverables while mitigating several sustainability-related issues with respect to greenhouse gas emissions, fossil fuel usage, land use change for fuel production and future food insufficiency. A new biorefinery-based integrated industrial ecology encompasses the different value chain of products, coproducts, and services from the biorefinery industries. This paper discusses a framework to integrate the algal biofuel-based biorefinery, a booming biofuel sector, with other industries such as livestock, lignocellulosic and aquaculture. Using the USA as an example, this paper also illustrates the benefits associated with sustainable production of fuel and food. Policy and regulatory initiatives for synergistic development of the algal biofuel sector with other industries can bring many sustainable solutions for the future existence of mankind.

Identification of aerobic gut bacteria from the kala azar vector, Phlebotomus argentipes: a platform for potential paratransgenic manipulation of sand flies.

Visceral leishmaniasis is an understudied parasitic disease responsible for significant global morbidity and mortality. We are presently investigating a method of disease prevention termed paratransgenesis. In this approach, symbiotic or commensal bacteria are transformed to produce anti-Leishmania molecules. The transformed bacteria are delivered back to sand flies to inactivate the parasite within the vector itself. In this study, we identified 28 distinct gut microorganisms from Phlebotomus argentipes trapped from four visceral leishmaniasis-endemic sites in India. A significant percent of Staphylococcus spp., environmental bacteria, and Enterobacteriaceae were identified. Two non-pathogenic organisms, Bacillus megaterium and Brevibacterium linens, were also isolated. Both organisms are also used extensively in industry. Our results indicate that B. megaterium and B. linens are possible candidates for use in a model of paratransgenesis to prevent transmission of Leishmania.