Effect of extracorporeal shock wave therapy on the microbial community in burn scars: retrospective case-control study.

BACKGROUND: The effectiveness of extracorporeal shock wave therapy (ESWT) has been demonstrated in various medical fields, including burn medicine. It promotes wound healing, improves blood flow, and modulates the inflammatory responses. The recovery speed and outcomes of skin diseases are influenced by the skin microbiome; however, studies examining the effects of specific treatments on the skin microbiome are lacking. This study investigated the impact of ESWT on the skin microbiome of burn patients, focusing on the microbial diversity and community structure within burn scars. MATERIALS AND METHODS: In the retrospective case-control study, nineteen patients with burn scars were treated with ESWT, and changes in their skin microbiome were evaluated. ESWT was administered weekly for three months, and samples were collected from the ESWT-treated burn scars and untreated normal skin. Blood chemistry, and pain and itching scores were evaluated during sample collection. The collected samples were then subjected to 16S rRNA sequencing. Microbial community analysis was conducted using the QIIME2 and R packages. RESULTS: After ESWT, changes in alpha diversity indices were observed in burn scars. Faith phylogenetic diversity (P<0.05) and observed features (P<0.01) increased, whereas the evenness index decreased (P<0.01); no marked changes were noted in untreated skin. Beta diversity analysis showed stable microbial community structures in both the treated and untreated areas. A considerable increase in Micrococcus and Staphylococcus abundance was observed. Network analysis revealed a more open microbial network structure after ESWT, indicating adaptive changes in the microbial community. CONCLUSION: ESWT enhances microbial diversity and modifies microbial community structure in burn scars, promoting a more balanced and functionally supportive microbiome. ESWT aids in scar remodeling and positively influences skin microbiome dynamics, contributing to improved skin health and recovery.

Combination non-targeted and sGRP78-targeted nanoparticle drug delivery outperforms either component to treat metastatic ovarian cancer.

Metastatic ovarian cancer (MOC) is highly deadly, due in part to the limited efficacy of standard-of-care chemotherapies to metastatic tumors and non-adherent cancer cells. Here, we demonstrated the effectiveness of a combination therapy of GRP78-targeted (TNPGRP78pep) and non-targeted (NP) nanoparticles to deliver a novel DM1-prodrug to MOC in a syngeneic mouse model. Cell surface-GRP78 is overexpressed in MOC, making GRP78 an optimal target for selective delivery of nanoparticles to MOC. The NP + TNPGRP78pep combination treatment reduced tumor burden by 15-fold, compared to untreated control. Increased T cell and macrophage levels in treated groups also suggested antitumor immune system involvement. The NP and TNPGRP78pep components functioned synergistically through two proposed mechanisms of action. The TNPGRP78pep targeted non-adherent cancer cells in the peritoneal cavity, preventing the formation of new solid tumors, while the NP passively targeted existing solid tumor sites, providing a sustained release of the drug to the tumor microenvironment.

Determination of personal exposure to volatile organic compounds and their health risks after the use of mosquito repellents in residential environments using passive sampling.

The ubiquitous use of mosquito repellents in homes across Asia, Africa, and South America is related with human exposure to indoor volatile organic compounds (VOCs). There are three primary types of mosquito repellents: those in the form of coils, mats, and liquids. The repellent mechanisms of these products are distinct, resulting in the generation of varying types of VOCs during the repellent process. In this study, the emission characteristics of commercial coil-, mat-, and liquid-type mosquito repellents were observed in a laboratory chamber using real-time measurement. A previously developed personal passive sampler, ePTFE PS, was used to quantify personal exposure to indoor VOCs while 86 volunteers habitually used those three representative types for 3 h in their residence. Notable increase of indoor benzene was observed for coil- and mat-type mosquito repellents, while α-pinene concentration increased significantly following the use of liquid-type mosquito repellent. The average incremental cancer risks for benzene were 10-6 to 10-4 for adults following the use of coil- and mat-type mosquito repellents. The average non-cancer risks for all chemicals were <1 after the use of three types of mosquito repellents. Considering the potential human health risks associated with byproducts (e.g., particulate matter or carbon monoxide from incomplete combustion) emitted after mosquito coil use, further research on this topic is warranted.

Radiosensitizing effect of a novel CTSS inhibitor by enhancing BRCA1 protein stability in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) patients harboring wild-type breast cancer susceptibility gene 1 (BRCA1) account for most TNBC patients but lack adequate targeted therapeutic options. Although radiotherapy (RT) is the primary treatment modality for TNBC patients, radioresistance is one of the major challenges. RT-induced increase in cathepsin S (CTSS) causes radioresistance through suppressing BRCA1-mediated apoptosis of tumor cells, which was induced by CTSS-mediated degradation of BRCA1. Targeting CTSS may provide a novel therapeutic opportunity for TNBC patients. Publicly available data and human tissue microarray slides were analyzed to investigate the relationship between CTSS and BRCA1 in breast cancer patients. A CTSS enzyme assay and in silico docking analysis were conducted to identify a novel CTSS inhibitor. RO5461111 was used first to confirm the concept of targeting CTSS for radiosensitizing effects. The MDA-MB-231 TNBC cell line was used for in vitro and in vivo assays. Western blotting, promoter assay, cell death assay, clonogenic survival assay, and immunohistochemistry staining were conducted to evaluate novel CTSS inhibitors. CTSS inhibitors were further evaluated for their additional benefit of inhibiting cell migration. A novel CTSS inhibitor, TS-24, increased BRCA1 protein levels and showed radiosensitization in TNBC cells with wild-type BRCA1 and in vivo in a TNBC xenograft mouse model. These effects were attributed by BRCA1-mediated apoptosis facilitated by TS-24. Furthermore, TS-24 demonstrated the additional effect of inhibiting cell migration. Our study suggests that employing CTSS inhibitors for the functional restoration of BRCA1 to enhance RT-induced apoptosis may provide a novel therapeutic opportunity for TNBC patients harboring wild-type BRCA1.

The preventive effect of Gastrodia elata Blume extract on vancomycin-induced acute kidney injury in rats.

BACKGROUND: Gastrodia elata Blume (GEB), a traditional medicinal herb, has been reported to have pharmacological effect including protection against liver, neuron and kidney toxicity. However, explanation of its underlying mechanisms remains a great challenge. This study investigated the protective effects of GEB extract on vancomycin (VAN)-induced nephrotoxicity in rats and underlying mechanisms with emphasis on the anti-oxidative stress, anti-inflammation and anti-apoptosis. The male Sprague-Dawley rats were randomly divided three groups: control (CON) group, VAN group and GEB group with duration of 14 days. RESULTS: The kidney weight and the serum levels of blood urea nitrogen and creatinine in the GEB group were lower than the VAN group. Histological analysis using hematoxylin & eosin and periodic acid Schiff staining revealed pathological changes of the VAN group. Immunohistochemical analysis revealed that the expression levels of N-acetyl-D-glucosaminidase, myeloperoxidase and tumor necrosis factor-alpha in the GEB group were decreased when compared with the VAN group. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells, phosphohistone and malondialdehyde levels were lower in the GEB group than VAN group. The levels of total glutathione in the GEB group were higher than the VAN group. CONCLUSIONS: The findings of this study suggested that GEB extract prevents VAN-induced renal tissue damage through anti-oxidation, anti-inflammation and anti-apoptosis.

A nanotherapeutic approach to selectively eliminate metastatic breast cancer cells by targeting cell surface GRP78.

Here, rational engineering of doxorubicin prodrug loaded peptide-targeted liposomal nanoparticles to selectively target metastatic breast cancer cells in vivo is described. Glucose-regulated protein 78 (GRP78), a heat shock protein typically localized in the endoplasmic reticulum in healthy cells, has been identified to home to the cell surface in certain cancers, and thus has emerged as a promising therapeutic target. Recent reports indicated GRP78 to be expressed on the cell surface of an aggressive subpopulation of stem-like breast cancer cells that exhibit metastatic potential. In this study, a targeted nanoparticle formulation with a GRP78-binding peptide (Kd of 7.4 ± 1.0 µM) was optimized to selectively target this subpopulation. In vitro studies with breast cancer cell lines showed the targeted nanoparticle formulation (TNPGRP78pep) achieved enhanced cellular uptake, while maintaining selectivity over the control groups. In vivo, TNPGRP78pep loaded with doxorubicin prodrug was evaluated using a lung metastatic mouse model and demonstrated inhibition of breast cancer cell seeding to lungs down at the level of negative control groups. Combined, this study established that specific-targeting of surface GRP78 expressing a subpopulation of aggressive breast cancer cells was able to inhibit breast cancer metastasis to lungs, and underpinned the significance of GRP78 in breast cancer metastasis.

Extramedullary plasmacytoma of the orbit with intracranial invasion: A case report.

RATIONALE: Plasmacytoma is a disease caused by the proliferation of monoclonal immunoglobulin-producing plasma cells and divided into multiple myeloma, solitary bone plasmacytoma, and extramedullary plasmacytoma. We report a case of orbital extramedullary plasmacytoma invading the dura mater in a patient with exophthalmos and diplopia. PATIENT CONCERNS: A 35-year-old female patient with exophthalmos in the right eye and diplopia visited the clinic. DIAGNOSES: The thyroid function tests showed nonspecific results. Orbital computed tomography and magnetic resonance imaging revealed a homogeneously enhancing orbital mass infiltrating the right maxillary sinus and adjacent brain tissue in the middle cranial fossa through the superior orbital fissure. INTERVENTIONS: To diagnose and alleviate the symptoms, an excisional biopsy was performed, which revealed a plasmacytoma. OUTCOMES: One month after the surgery, the protruding symptoms and eye movement restriction in the right eye improved, and the visual acuity in the right eye was restored. LESSONS: In this case report, we present a case of an extramedullary plasmacytoma that originated in the inferior wall of the orbit and invaded the cranial cavity. To our knowledge, no previous reports have described a solitary plasmacytoma that originated in the orbit, causing exophthalmos and invading the cranial cavity at the same time.

Integrated miRNA Changes in Canine Testis and Epididymis According to Age and Presence of Cryptorchidism.

In the present study, we aimed to investigate age-, cryptorchidism-, and testicular tumor-related changes in miRNAs in the testis and epididymis of dogs. Twelve healthy male dogs were divided into two groups: young (<1 year, n = 8) and old (>3 years, n = 4). Five dogs with unilateral cryptorchidism, one with a Sertoli cell tumor, and one with seminoma were referred to a veterinary hospital. After surgery, the testes and epididymis tails were collected. A high-throughput miRNA array analysis was performed to identify miRNAs affected by age, cryptorchidism, and testicular tumors. The expression of only cfa-miR-503 was downregulated in the epididymis of younger dogs, whereas the expression of 64 miRNAs was upregulated. Among them, the top five miRNAs were cfa-miR-26a, cfa-miR-200c, cfa-let-7c, cfa-let-7b, and cfa-let-7a. The expression of cfa-miR-148a and cfa-miR-497 was considerably lower in cryptorchid testis than in healthy dog testis. In the epididymis, the cfa-miR-1841 level was significantly decreased. We observed a significant difference in the expression of 26 cfa-miRNAs between testicular tumors and normal tissues. This study demonstrated that aging and cryptorchidism have a causal relationship with miRNA expression. The identified miRNAs may be candidate genes for male reproductive traits and could be applied in molecular breeding programs.

Determination of terpene levels after the use of essential oil diffusers in vehicles and studio apartments using passive sampling.

The exposure levels of selected terpenes (limonene, α- and ß-pinenes, and γ-terpinene) emitted by essential oil diffusers in vehicles and studio apartments were assessed using a passive sampling method. A previously developed passive sampler composed of an expanded polytetrafluoroethylene membrane and adsorbent (ePTFE PS) was enlarged and made wearable. Before field deployment, the sampling performance of the modified ePTFE PS for selected terpenes was compared with that of active sampling in a lab-scale 5 m3 test chamber under constant exposure conditions, supporting that passive sampling provides reasonable estimates of the time-weighted exposure concentration. Fifty volunteers were recruited and asked to wear the ePTFE PS while using an essential oil diffuser inside their own vehicle while commuting and in their studio apartment while sleeping. Terpene levels without an essential oil diffuser were very low in vehicles and 47, 3.6, 1.6, and 0.62 µg m-3 for average concentrations of limonene, α- and ß-pinenes, and γ-terpinene in studio apartments, respectively, close to those reported in previous studies. The indoor concentrations of all selected terpenes in vehicles and studio apartments were elevated by the use of essential oil diffusers, especially in vehicles. The average concentration of limonene in vehicles after the use of essential oil diffusers was 11 µg m-3, which was greater than that before use by a factor of 30. Therefore, cautious usage of essential oil diffusers indoors where the volume is limited, such as a vehicle, is needed to reduce exposure to terpenes.

Dietary regulations for microbiota dysbiosis among post-menopausal women with type 2 diabetes.

Type 2 diabetes (T2D) and T2D-associated comorbidities, such as obesity, are serious universally prevalent health issues among post-menopausal women. Menopause is an unavoidable condition characterized by the depletion of estrogen, a gonadotropic hormone responsible for secondary sexual characteristics in women. In addition to sexual dimorphism, estrogen also participates in glucose-lipid homeostasis, and estrogen depletion is associated with insulin resistance in the female body. Estrogen level in the gut also regulates the microbiota composition, and even conjugated estrogen is actively metabolized by the estrobolome to maintain insulin levels. Moreover, post-menopausal gut microbiota is different from the pre-menopausal gut microbiota, as it is less diverse and lacks the mucolytic Akkermansia and short-chain fatty acid (SCFA) producers such as Faecalibacterium and Roseburia. Through various metabolites (SCFAs, secondary bile acid, and serotonin), the gut microbiota plays a significant role in regulating glucose homeostasis, oxidative stress, and T2D-associated pro-inflammatory cytokines (IL-1, IL-6). While gut dysbiosis is common among post-menopausal women, dietary interventions such as probiotics, prebiotics, and synbiotics can ease post-menopausal gut dysbiosis. The objective of this review is to understand the relationship between post-menopausal gut dysbiosis and T2D-associated factors. Additionally, the study also provided dietary recommendations to avoid T2D progression among post-menopausal women.

Design, synthesis, and biological evaluation of novel HSP27 inhibitors to sensitize lung cancer cells to clinically available anticancer agents.

Expression of heat shock protein (HSP) correlates with the oncogenic status of malignant cells and plays an important role in tumorigenesis. HSP27 is constitutively expressed at specific stages of cancer development, and several clinical trials have reported correlations between HSP27 expression and tumor progression, metastasis, and chemoresistance in various types of cancer cells. These findings indicate that HSP27 is a major drug target, particularly in chemo-resistant cancers. As part of our ongoing efforts to improve the previously identified J2, a HSP27 cross-linker, we, in this study, report the identification of NK16 as a novel inducer of abnormal HSP27 dimers that did not affect the expression of HSP90 in an NCI-H460 lung cancer cell model. When NCI-H460 cells were treated with NK16 in combination with the anticancer drug cisplatin or paclitaxel, cleavage of PARP and caspase-3 was increased compared to administration of cisplatin or paclitaxel alone. Similar results were obtained in an NCI-H460-xenografted mouse model, in which tumor growth was suppressed more by co-administration of NK16 and paclitaxel than by paclitaxel alone. We propose NK16 as a meaningful strategy to improve the anticancer efficacy of cisplatin and paclitaxel.

Disease-driven engineering of peptide-targeted DM1 loaded liposomal nanoparticles for enhanced efficacy in treating multiple myeloma by exploring DM1 prodrug chemistry.

Here, we report a CD138 receptor targeting liposomal formulation (TNP[Prodrug-4]) that achieved efficacious tumor growth inhibition in treating multiple myeloma by overcoming the dose limiting severe toxicity issues of a highly potent drug, Mertansine (DM1). Despite the promising potential to treat various cancers, due to poor solubility and pharmacokinetic profile, DM1's translation to the clinic has been unsatisfactory. We hypothesized that the optimal prodrug chemistry would promote efficient loading of the prodrug into targeted nanoparticles and achieve controlled release following endocytosis by the cancer cells, consequently, accomplish the most potent tumor growth inhibition. We evaluated four functional linker chemistries for synthesizing DM1-Prodrug molecules and evaluated their stability and cancer cell toxicity in vitro. It was determined that the phosphodiester moiety, as part of nanoparticle formulations, demonstrated most favorable characteristics with an IC50 of ∼16 nM. Nanoparticle formulations of Prodrug-4 enabled its administration at 8-fold higher dosage of equivalent free drug while remaining below maximum tolerated dose. Importantly, TNP[Prodrug-4] achieved near complete inhibition of tumor growth (∼99% by day 10) compared to control, without displaying noticeable systemic toxicity. TNP[Prodrug-4] promises a formulation that could potentially make DM1 treatment available for wider clinical applications with a long-term goal for better patient outcomes.

Synthesis and evaluation of 7-(3-aminopropyloxy)-substituted flavone analogue as a topoisomerase IIα catalytic inhibitor and its sensitizing effect to enzalutamide in castration-resistant prostate cancer cells.

Prostate cancer patients primarily receive androgen receptor (AR)-targeted drugs as a primary treatment option because prostate cancer is associated with highly activated AR signaling. AR amplification made prostate cancer cells viable under treatment of AR-targeted therapy, leading to castration resistance. AR amplification was more common in enzalutamide-resistant patients. As a strategy to overcome castration resistance and to improve the efficacy of enzalutamide, second-generation nonsteroidal antiandrogen drugs for castration-resistant prostate cancer (CRPC) including topoisomerase II (topo II) poisons such as etoposide and mitoxantrone, have been administered in combination with enzalutamide. In the present study, it was confirmed that amplification of topo IIα, but not I and IIß, was directly and proportionally associated with poor clinical outcome of Prostate cancer. Among a novel series of newly designed and synthesized 7-(3-aminopropyloxy)-substituted flavone analogues, compound 6, the most potent derivative, was further characterized and identified as a topo IIα catalytic inhibitor that intercalates into DNA and binds to the DNA minor groove with better efficacy and less genotoxicity than etoposide, a topo II poison. Compound 6 showed remarkable efficacy in inhibiting AR-negative CRPC cell growth and sensitizing activity to enzalutamide in AR-positive CRPC cells, thus confirming the potential of topo IIα catalytic inhibitor to overcome resistance to androgen deprivation therapy.

Mulberry Leaf Supplements Effecting Anti-Inflammatory Genes and Improving Obesity in Elderly Overweight Dogs.

Overweight and obesity, associated with various health complications, refer to abnormal or excessive fat accumulation conditions that harm health. Like humans, obesity is a growing problem in dogs, which may increase the risk of serious diseases such as diabetes and cancer. Mulberry leaf has shown potential anti-obesity and anti-diabetes effects in several studies. Our research studied the impact of mulberry leaf supplements in healthy old overweight dogs for 12 weeks. Blood and fecal samples were collected from the dogs before and after treatment for different analyses, including whole transcriptome and gut microbiome analysis. The Body Condition Score (BCS) and blood glucose levels were significantly decreased in all mulberry treatment groups, which justifies the anti-obesity effect of mulberry leaf in dogs. Throughout the whole transcriptome study, the downregulation of PTX3 and upregulation of PDCD-1, TNFRSF1B, RUNX3, and TICAM1 genes in the high mulberry group were found, which have been associated with anti-inflammatory effects in the literature. It may be an essential gene expression mechanism responsible for the anti-inflammatory and, subsequently, anti-obesity effects associated with mulberry leaf treatment, as confirmed by real-time polymerase chain reaction analysis. In microbiome analysis, Papillibacter cinnamivorans, related to the Mediterranean diet, which may cause anti-inflammatory effects, were abundant in the same treatment group. Further studies may be required to establish the gene expression mechanism and role of abundant bacteria in the anti-obesity effect of mulberry supplements in dogs. Overall, we propose mulberry leaves as a portion of food supplements for improving blood glucose levels and the anti-inflammation of blood in companion dogs.

Cyanidin-3-O-Glucoside Regulates the M1/M2 Polarization of Microglia via PPARγ and Aß42 Phagocytosis Through TREM2 in an Alzheimer's Disease Model.

Microglial polarization plays an essential role in the progression and regression of neurodegenerative disorders. Cyanidin-3-O-glucoside (C3G), a dietary anthocyanin found in many fruits and vegetables, has been reported as an antioxidant, anti-inflammatory, and antitumor agent. However, there have been no reports on whether C3G can regulate the M1/M2 shift in an Alzheimer's disease model. We attempted to investigate the effects of C3G on M1/M2 polarization and the mechanism to regulate anti-inflammation and phagocytosis, both in vitro and in vivo. HMC3 cells were treated with ß-amyloid (Aß42) in the presence or absence of 50 µM C3G for different time intervals, and APPswe/PS1ΔE9 mice were orally administered 30 mg/kg/day of C3G for 38 weeks. The in vitro data revealed that C3G could shift the M1 phenotype of microglia to M2 by reducing the expression of M1-specific markers (CD86 and CD80), inflammatory cytokines (IL-Iß, IL-6, TNF-α), reactive oxygen species, and enhancing the expression of M2-specific markers (CD206 and CD163). The APPswe/PS1ΔE9 mice results were consistent with the in vitro data, indicating a significant reduction in inflammatory cytokines and higher expression of M2-specific markers such as CD206 and Arg1 in C3G-treated Alzheimer's disease model mice. Additionally, C3G was found to upregulate PPARγ expression levels both in vitro and in vivo, whereas a PPARγ antagonist (GW9662) was found to block C3G-mediated effects in vitro. In this study, we confirmed that C3G could regulate microglial polarization by activating PPARγ and eliminating accumulated ß-amyloid by enhancing Aß42 phagocytosis through the upregulation of TREM2.

An excitation wavelength-optimized, stable SERS biosensing nanoplatform for analyzing adenoviral and AstraZeneca COVID-19 vaccination efficacy status using tear samples of vaccinated individuals.

We introduce a label-free surface-enhanced Raman scattering (SERS) biosensing platform equipped with metallic nanostructures that can identify the efficacy of Oxford-AstraZeneca (AZD1222) vaccine in vaccinated individuals using non-invasive tear samples. We confirmed the hypothesis that the tears of people who receive the AZD1222 vaccine may be similar to those of adenovirus epidemic keratoconjunctivitis patients since the Oxford-AstraZeneca vaccine is derived from a replication-deficient ChAdOx1 vector of chimpanzee adenovirus. Additionally, we confirmed the potential of the three markers for estimating the vaccination status via analyzing the signals emanating from antibodies or immunoglobulin G by-product using our label-free, SERS biosensing technique with a high reproducibility (<3% relative standard deviation), femtomole-scale limit of detection (1 × 10-14 M), and high SERS response of >108. Therefore, our label-free SERS biosensing nanoplatforms with long-term storage and robust stability will enable rapid and robust monitoring of the vaccine presence in vaccinated individuals.

Physicochemical properties, antioxidant activities and microbial communities of Ethiopian honey wine, Tej.

Ethiopian honey wine, Tej, is spontaneously fermented traditional alcoholic beverage, usually made from honey and "gesho" (Rhamnus prinoides). Till now, limited amount of information is available on the characterization of Tej. Thus, the aim of this paper is to reveal the microbiological diversity and physicochemical properties of Tej samples collected from different areas of Ethiopia. High-throughput sequencing, electrochemical and chromatographic techniques, and spectrophotometric methods were used to achieve these objectives. Although there was a statistical difference in the exact values of physicochemical properties between the collected Tej samples, the pH and titratable acidity values of the samples ranged from 2.8 to 3.8 and from 1.81 to 8.65 g/L, respectively. Similarly, the alcohol and sugar contents of the samples were in the range of 6.36-11.34 g/100 mL and from 0.37 to 31.6 g/L, respectively. Moreover, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS) values of the samples were in the range of 37.9-81.0% and 27.4-73.1%, respectively. Furthermore, microbial community structure was predominated by a few fermentative microorganisms. Specifically, the bacterial community structure was dominated by the genera of Lactobacillus (53.15%) and Zymomonas (38.41%). Whereas, the fungal community structure was exclusively dominated by genus of Saccharomyces (99.66%). Additionally, Lactobacillus, Zymomonas and Saccharomyces were the detected core microbiome for the collected Tej samples. Both bacterial and fungal communities had shown no statistically significant differences in alpha diversity analysis based on the area of sample collection. However, the bacterial communities had a statically significant difference in Unweighted Unifrac beta diversity analysis. Generally, the observed shared physicochemical characteristic features and the dominance by certain group of microorganisms might be seen as a boon for the development of direct fermentation system to this traditional alcoholic beverage.

Alterations and Prediction of Functional Profiles of Gut Microbiota After Fecal Microbiota Transplantation for Iranian Recurrent Clostridioides difficile Infection with Underlying Inflammatory Bowel Disease: A Pilot Study.

BACKGROUND AND PURPOSE: Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT. PATIENTS AND METHODS: FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis. RESULTS: Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors. CONCLUSION: FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.

Butyrate producers, "The Sentinel of Gut": Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics.

Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most butyrate producers belong to the Clostridium cluster of the phylum Firmicutes, such as Faecalibacterium, Roseburia, Eubacterium, Anaerostipes, Coprococcus, Subdoligranulum, and Anaerobutyricum. They metabolize carbohydrates via the butyryl-CoA: acetate CoA-transferase pathway and butyrate kinase terminal enzymes to produce most of butyrate. Although, in minor fractions, amino acids can also be utilized to generate butyrate via glutamate and lysine pathways. Butyrogenic microbes play a vital role in various gut-associated metabolisms. Butyrate is used by colonocytes to generate energy, stabilizes hypoxia-inducible factor to maintain the anaerobic environment in the gut, maintains gut barrier integrity by regulating Claudin-1 and synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), and inhibits oncogenic pathways (Akt/ERK, Wnt, and TGF-ß signaling). Colonic butyrate producers shape the gut microbial community by secreting various anti-microbial substances, such as cathelicidins, reuterin, and ß-defensin-1, and maintain gut homeostasis by releasing anti-inflammatory molecules, such as IgA, vitamin B, and microbial anti-inflammatory molecules. Additionally, butyrate producers, such as Roseburia, produce anti-carcinogenic metabolites, such as shikimic acid and a precursor of conjugated linoleic acid. In this review, we summarized the significance of butyrate, critically examined the role and relevance of butyrate producers, and contextualized their importance as microbial therapeutics.

Anti-diabetic prospects of dietary bio-actives of millets and the significance of the gut microbiota: A case of finger millet.

Finger millet (Eleusine coracana) is a staple food in several parts of the world because of its high nutritional value. In addition to its high nutrient content, finger millet contains numerous bioactive compounds, including polyphenol (10.2 mg/g TAE), flavonoid (5.54 mg/g CE), phytic acid (0.48%), and dietary fiber (15-20%). Polyphenols are known for their anti-oxidant and anti-diabetic role. Phytic acid, previously considered an anti-nutritive substance, is now regarded as a nutraceutical as it reduces carbohydrate digestibility and thus controls post-prandial glucose levels and obesity. Thus, finger millet is an attractive diet for patients with diabetes. Recent findings have revealed that the anti-oxidant activity and bio-accessibility of finger millet polyphenols increased significantly (P < 0.05) in the colon, confirming the role of the gut microbiota. The prebiotic content of finger millet was also utilized by the gut microbiota, such as Faecalibacterium, Eubacterium, and Roseburia, to generate colonic short-chain fatty acids (SCFAs), and probiotic Bifidobacterium and Lactobacillus, which are known to be anti-diabetic in nature. Notably, finger millet-induced mucus-degrading Akkermansia muciniphila can also help in alleviate diabetes by releasing propionate and Amuc_1100 protein. Various millet bio-actives effectively controlled pathogenic gut microbiota, such as Shigella and Clostridium histolyticum, to lower gut inflammation and, thus, the risk of diabetes in the host. In the current review, we have meticulously examined the role of gut microbiota in the bio-accessibility of millet compounds and their impact on diabetes.