Deciphering the Role of the Gut Microbiota in Exposure to Emerging Contaminants and Diabetes: A Review.

Emerging pollutants, a category of compounds currently not regulated or inadequately regulated by law, have recently become a focal point of research due to their potential toxic effects on human health. The gut microbiota plays a pivotal role in human health; it is particularly susceptible to disruption and alteration upon exposure to a range of toxic environmental chemicals, including emerging contaminants. The disturbance of the gut microbiome caused by environmental pollutants may represent a mechanism through which environmental chemicals exert their toxic effects, a mechanism that is garnering increasing attention. However, the discussion on the toxic link between emerging pollutants and glucose metabolism remains insufficiently explored. This review aims to establish a connection between emerging pollutants and glucose metabolism through the gut microbiota, delving into the toxic impacts of these pollutants on glucose metabolism and the potential role played by the gut microbiota.

Emerging Contaminants: An Emerging Risk Factor for Diabetes Mellitus.

Emerging contaminants have been increasingly recognized as critical determinants in global public health outcomes. However, the intricate relationship between these contaminants and glucose metabolism remains to be fully elucidated. The paucity of comprehensive clinical data, coupled with the need for in-depth mechanistic investigations, underscores the urgency to decipher the precise molecular and cellular pathways through which these contaminants potentially mediate the initiation and progression of diabetes mellitus. A profound understanding of the epidemiological impact of these emerging contaminants, as well as the elucidation of the underlying mechanistic pathways, is indispensable for the formulation of evidence-based policy and preventive interventions. This review systematically aggregates contemporary findings from epidemiological investigations and delves into the mechanistic correlates that tether exposure to emerging contaminants, including endocrine disruptors, perfluorinated compounds, microplastics, and antibiotics, to glycemic dysregulation. A nuanced exploration is undertaken focusing on potential dietary sources and the consequential role of the gut microbiome in their toxic effects. This review endeavors to provide a foundational reference for future investigations into the complex interplay between emerging contaminants and diabetes mellitus.

Characterizing the Gut Microbial Metabolic Profile of Mice with the Administration of Berry-Derived Cyanidin-3-Glucoside.

Dietary modulation of the gut microbiota has recently received considerable attention. It is well established that consumption of berries confers a number of health benefits. We previously reported that a black raspberry (BRB)-rich diet effectively modulates the gut microbiota. Given the role of anthocyanins in the health benefits of berries, coupled with interactions of gut microbial metabolites with host health, the objective of this follow-up study was to further characterize the profile of functional metabolites in the gut microbiome modulated by anthocyanins. We utilized a berry-derived classic anthocyanin, cyanidin-3-glucoside (C3G), combined with a mouse model to probe C3G-associated functional metabolic products of gut bacteria through a mass spectrometry-based metabolomic profiling technique. Results showed that C3G substantially changed the gut microbiota of mice, including its composition and metabolic profile. A distinct metabolic profile in addition to a variety of key microbiota-related metabolites was observed in C3G-treated mice. Microbial metabolites involved in protein digestion and absorption were differently abundant between C3G-treated and control mice, which may be linked to the effects of berry consumption. Results of the present study suggest the involvement of the gut microbiota in the health benefits of C3G, providing evidence connecting the gut microbiota with berry consumption and its beneficial effects.

Are Microplastics Toxic? A Review from Eco-Toxicity to Effects on the Gut Microbiota.

Emerging studies have presented an initial picture of the toxic effects of exposure to environmental micro- and nanoplastics. They have indicated that micro- and nanoplastics may induce toxicity by leading to oxidative stress, energy metabolism disorders, gene damage, and so forth in environmental organisms, marine invertebrates and vertebrates, and laboratory mouse models. In recent years, micro- and nanoplastics have been discovered in human fecal samples, placentas, lung tissue, and even blood; thus, micro- and nanoplastics pose an alarming and ever-increasing threat to global public health. However, current research on the health effects of micro- and nanoplastics and the possible adverse outcomes in humans has only presented the tip of the iceberg. More robust clinical data and basic experiments are still warranted to elucidate the specific relationships and mechanisms. In this paper, we review studies on micro- and nanoplastic toxicity from the perspectives of eco-toxicity, the adverse effects on invertebrates and vertebrates, and the impact of micro- and nanoplastics on the gut microbiota and its metabolites. In addition, we evaluate the toxicological role of micro- and nanoplastic exposure and its potential implications in respect to human health. We also summarize studies regarding preventive strategies. Overall, this review provides insights on micro- and nanoplastic toxicity and its underlying mechanisms, opening up scientific avenues for future in-depth studies.

Deciphering Gut Microbiome Responses upon Microplastic Exposure via Integrating Metagenomics and Activity-Based Metabolomics.

Perturbations of the gut microbiome are often intertwined with the onset and development of diverse metabolic diseases. It has been suggested that gut microbiome perturbation could be a potential mechanism through which environmental chemical exposure induces or exacerbates human diseases. Microplastic pollution, an emerging environmental issue, has received ever increasing attention in recent years. However, interactions between microplastic exposure and the gut microbiota remain elusive. This study aimed to decipher the responses of the gut microbiome upon microplastic polystyrene (MP) exposure by integrating 16S rRNA high-throughput sequencing with metabolomic profiling techniques using a C57BL/6 mouse model. The results indicated that MP exposure significantly perturbed aspects of the gut microbiota, including its composition, diversity, and functional pathways that are involved in xenobiotic metabolism. A distinct metabolite profile was observed in mice with MP exposure, which probably resulted from changes in gut bacterial composition. Specifically, untargeted metabolomics revealed that levels of metabolites associated with cholesterol metabolism, primary and secondary bile acid biosynthesis, and taurine and hypotaurine metabolism were changed significantly. Targeted approaches indicated significant perturbation with respect to the levels of short-chain fatty acids derived from the gut microbiota. This study can provide evidence for the missing link in understanding the mechanisms behind the toxic effects of microplastics.

Dietary Administration of Black Raspberries and Arsenic Exposure: Changes in the Gut Microbiota and Its Functional Metabolites.

Mounting evidence has linked berries to a variety of health benefits. We previously reported that administration of a diet rich in black raspberries (BRBs) impacted arsenic (As) biotransformation and reduced As-induced oxidative stress. To further characterize the role of the gut microbiota in BRB-mediated As toxicity, we utilized the dietary intervention of BRBs combined with a mouse model to demonstrate microbial changes by examining associated alterations in the gut microbiota, especially its functional metabolites. Results showed that BRB consumption changed As-induced gut microbial alterations through restoring and modifying the gut microbiome, including its composition, functions and metabolites. A number of functional metabolites in addition to bacterial genera were significantly altered, which may be linked to the effects of BRBs on arsenic exposure. Results of the present study suggest functional interactions between dietary administration of black raspberries and As exposure through the lens of the gut microbiota, and modulation of the gut microbiota and its functional metabolites could contribute to effects of administration of BRBs on As toxicity.

Promoting effect of long non-coding RNA SNHG1 on osteogenic differentiation of fibroblastic cells from the posterior longitudinal ligament by the microRNA-320b/IFNGR1 network.

Long non-coding RNAs (lncRNAs) have been noted to influence the progression of ossification of posterior longitudinal ligament (OPLL). The work aims to probe the effect of lncRNA SNHG1 on osteogenic differentiation of ligament fibroblastic cells (LFCs). Aberrantly expressed lncRNAs in ossified PLL tissues were screened out by microarray analysis. Gain- and loss-of function experiments of SNHG1 were performed to identify its role in osteogenic differentiation of LFCs. The downstream molecules of SNHG1 were explored. Altered expression of miR-320b was introduced in LFCs as well. The interactions among SNHG1, miR-320b and IFNGR1 were identified. Consequently, SNHG1 was found highly expressed in OPLL patients. Silencing of SNHG1 inhibited BMP-2, RUNX2 and OCN expression and the ALP activity and reduced osteogenic differentiation of LFCs. Importantly, SNHG1 could and upregulate IFNGR1 through serving as a sponge for miR-320b. Over-expression of miR-320b inhibited osteogenic differentiation of LFCs and inactivated the JAK/STAT signaling pathway. Further administration of Fedratinib, a JAK2-specific agonist, increased osteogenic differentiation of LFCs. To conclude, the study suggested that SNHG1 could upregulate IFNGR1 by sequestering miR-320b and activate the JAK/STAT signaling. Silencing of SNHG1 could reduce the osteogenic differentiation and mineralization of LFCs. The study may offer new insights into OPLL treatment.

Novel compound heterozygous GFPT1 mutations in a family with limb-girdle myasthenia with tubular aggregates.

Limb-girdle myasthenia with tubular aggregates, a subtype of congenital myasthenic syndrome, is an extremely rare autosomal recessive genetic disease characterized by prominent limb-girdle weakness and good response to acetylcholinesterase inhibitor therapy. Herein, we reported two novel mutations of GFPT1 gene in a Chinese pedigree. Two siblings presented with fatigue, weakness of limb-girdle and decrement of the muscle action potential with repetitive nerve stimulation. Thus, myasthenia gravis was initially suspected, but anti-AChR antibodies were negative. Two novel missense mutations (p.Lys154Asn and p.Asn363Ser) in GFPT1 were identified through genetic testing conducted on 167 well-established genes associated with muscular diseases by targeted high throughput sequencing. Both mutations have not been recorded in the dsSNP database, Exome Aggregation Consortium database and 1000 Genomes Project database. The mutation sites were co-segregated with the phenotype and conserved between the different species. The mutations were not found in the 200 unrelated normal controls. Muscle biopsies revealed tubular aggregates, in accordance with previous reports with GFPT1 mutations. Subsequently, dramatic improvement in strength occurred following anti-cholinesterase therapy. Our study will be helpful for the diagnosis and treatment for Limb-girdle myasthenia with tubular aggregates.

[Inhibitory effect of extract of Coptidis Rhizoma on invasion of Candida albicans hyphae in vitro].

The aim of this paper was to investigate the inhibitory effect of extract of Coptidis Rhizoma(ECR) on invasion of Candida albicans hyphae in vitro.XTT reduction method was used to evaluate the metabolic activity of C.albicans.The colony edge growth of C.albicans was observed by solid medium.The growth of C.albicans hyphae was determined on semi-solid medium.The morphology and viability changes of C.albicans hyphae were assessed by scanning electron microscope and fluorescence microscope.qRT-PCR method was used to detect the ALS3 and SSA1 expression of C.albicans invasin genes.The results showed that the metabolic viability by XTT method detected that the activity of C.albicans was gradually decreased under the intervention of 64,128 and 256 mg·L-1 of ECR respectively.128,256 mg·L-1 of ECR significantly inhibited colony folds and wrinkles on solid medium and the hyphal invasion in semi-solid medium.Scanning electron microscopy and fluorescence microscopy showed that 128,256 mg·L-1 of ECR could inhibit the formation of C.albicans hyphae.qRT-PCR results showed that the expression of invasin gene ALS3 and SSA1 was down-regulated,and especially 256 mg·L-1 of ECR could down-regulate the two genes expression by 4.8,1.68 times respectively.This study showed that ECR can affect the invasiveness of C.albicans by inhibiting the growth of hyphae and the expression of invasin.

Nine-hole Peg Test and Ten-meter Walk Test for Evaluating Functional Loss in Chinese Charcot-Marie-Tooth Disease.

BACKGROUND: The 9-hole peg test (9-HPT) and 10-meter walk test (10-MWT) are commonly used to test finger motor function and walking ability. The aim of this present study was to investigate the efficacy of these tests for evaluating functional loss in Chinese Charcot-Marie-Tooth (CMT) disease. METHODS: Thirty-four Chinese CMT patients (CMT group) from August 2015 to December 2016 were evaluated with 9-HPT, 10-MWT, CMT disease examination score, overall neuropathy limitation scale (ONLS), functional disability score, and Berg Balance Scale (BBS). Thirty-five age- and gender-matched healthy controls (control group) were also included in the study. Student's nonpaired or paired t-test were performed to compare data between two independent or related groups, respectively. The Pearson test was used to examine the correlations between recorded parameters. RESULTS: The mean 9-HPT completion time in the dominant hand of CMT patients was significantly slower than that in the healthy controls (29.60 ± 11.89 s vs. 19.58 ± 3.45 s; t = -4.728, P < 0.001). Women with CMT completed the 9-HPT significantly faster than men with CMT (dominant hand: 24.74 ± 7.93 s vs. 33.01 ± 13.14 s, t = 2.097, P = 0.044). The gait speed of the average self-selected velocity and the average fast-velocity assessed using 10-MWT for CMT patients were significantly slower than those in the control group (1.03 ± 0.18 m/s vs. 1.44 ± 0.17 m/s, t = 9.333, P < 0.001; 1.31 ± 0.30 m/s vs. 1.91 ± 0.25 m/s, t = 8.853, P < 0.001, respectively). There was no difference in gait speed between men and women. Both 9-HPT and 10-MWT were significantly correlated with the ONLS, functional disability score, and BBS (P < 0.05 for all). CONCLUSION: The 9-HPT and 10-MWT might be useful for functional assessment in Chinese patients with CMT.

Metabolomics method based on ultra high performance liquid chromatography with time-of-flight mass spectrometry to analyze toxins in fresh and dried toad venom.

Drying is a critical step to prolong the storage time in natural medicine processing but it changes the chemical characteristics of the product. In this study, research was performed to characterize the metabolomic changes in toad venom induced by vacuum-drying at 60°C and air-drying at room temperature by ultra high performance liquid chromatography coupled with pattern recognition approaches. In total 52 metabolites, down-regulated or up-regulated, were identified as potential chemical markers. Compared with fresh toad venom, vacuum-drying at 60°C succeeded in raising the conjugated-type bufadienolide content significantly, while the content of free-type bufadienolides were slightly reduced. On the other hand, toad venom air-dried at room temperature presented a relatively low amount of bufadienolides compared with fresh venom. For example, the content of several known anti-tumor components (gamabufotalin, bufotalin, cinobufagin, etc.) were significantly reduced. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide bioassay further showed that venom air-dried at room temperature had weaker anti-tumor activity on human hepatocellular carcinoma SMMC-7721 proliferation in vitro than samples vacuum-dried at 60°C. These results showed that the great metabolomic changes of toad venom occurred during the drying process, suggesting that a proper drying procedure is important for sustaining the chemical quality of natural medicines.

Exome sequencing reveals novel SPG11 mutation in hereditary spastic paraplegia with complicated phenotypes.

We used a combined approach of whole-exome sequencing and candidate mutation validation to identify the disease-causing gene in a hereditary spastic paraplegia (HSP) patient with lower motor neuron involvement, mild cerebellar signs and dysgenesis of the corpus callosum. HSP is a clinically and genetically heterogeneous neurodegenerative disorder characterized by degeneration of the corticospinal tract motor neurons and resulting in progressive lower limb spasticity, often with a complicated phenotype. We identified novel compound heterozygous mutations in the SPG11 gene in this patient as follows: a mutation in exon 32, c.6194C > G transition (p.S2056X) and a novel c.5121+1C > T splicing mutation. Our finding suggests that these novel compound heterozygous mutations in SPG11 are associated with HSP and lower motor neuron involvement, mild cerebellar signs and dysgenesis of the corpus callosum. This study also demonstrates that exome sequencing is an efficient and rapid diagnostic tool for identifying the causes of some complex and genetically heterogeneous neurodegenerative diseases.

Nerve growth factor for the treatment of spinocerebellar ataxia type 3: an open-label study.

BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA worldwide, and runs a slowly progressive and unremitting disease course. There is currently no curable treatment available. Growing evidence has suggested that nerve growth factor (NGF) may have therapeutic effects in neurodegenerative diseases, and possibly also in SCA3. The objective of this study was to test the efficacy of NGF in SCA3 patients. METHODS: We performed an open-label prospective study in genetically confirmed adult (>18 years old) SCA3 patients. NGF was administered by intramuscular injection (18 µg once daily) for 28 days consecutively. All the patients were evaluated at baseline and 2 and 4 weeks after treatment using the Chinese version of the scale for assessment and rating of ataxia (SARA). RESULTS: Twenty-one SCA3 patients (10 men and 11 women, mean age 39.14 ± 7.81 years, mean disease duration 4.14 ± 1.90 years, mean CAG repeats number 77.57 ± 2.27) were enrolled. After 28 days of NGF treatment, the mean total SARA score decreased significantly from a baseline of 8.48 ± 2.40 to 6.30 ± 1.87 (P < 0.001). Subsections SARA scores also showed significant improvements in stance (P = 0.003), speech (P = 0.023), finger chase (P = 0.015), fast alternating hand movements (P = 0.009), and heel-shin slide (P = 0.001). CONCLUSIONS: Our preliminary data suggest that NGF may be effective in treating patients with SCA3.

Reliability and validity of the Chinese version of the Scale for Assessment and Rating of Ataxia.

BACKGROUND: The Scale for the Assessment and Rating of Ataxia (SARA) was shown to be a reliable and valid measurement for patients with spinocerebellar ataxia (SCA). The Brazilian version and the Japanese version of SARA were favorable for good reliability and validity. This study aimed to translate SARA into Chinese and test its reliability and validity in measurement of cerebellar ataxia. METHODS: SARA was translated into Chinese. A total 39 patients with degeneration cerebellar ataxia were evaluated independently by two neurologists with the Chinese version of SARA. Then the patients were evaluated by one of above neurologists with International Cooperative Ataxia Rating Scale (ICARS). The statistical analyses were performed using SPSS 17.0 for Windows. RESULTS: The Cronbach's alpha coefficient of the Chinese version of SARA was 0.78, which represents a good internal consistence. The correlation coefficient of the Chinese version of SARA scores between the two evaluators was 0.86, illustrating that the inter-rater reliability of Chinese version of SARA was good. The correlation coefficient between the Chinese version of SARA and ICARS was 0.91, illustrating that the criterion validity of Chinese version of SARA was not bad. CONCLUSIONS: The Chinese version of SARA is reliable and effective for the assessment of degeneration cerebellar ataxia. Compared with ICARS, the evaluation of Chinese version of SARA is more objective, the assessment time is shortened, and the maneuverability is better.