IFN-stimulated metabolite transporter ENT3 facilitates viral genome release.

An increasing amount of evidence emphasizes the role of metabolic reprogramming in immune cells to fight infections. However, little is known about the regulation of metabolite transporters that facilitate and support metabolic demands. In this study, we found that the expression of equilibrative nucleoside transporter 3 (ENT3, encoded by solute carrier family 29 member 3, Slc29a3) is part of the innate immune response, which is rapidly upregulated upon pathogen invasion. The transcription of Slc29a3 is directly regulated by type I interferon-induced signaling, demonstrating that this metabolite transporter is an interferon-stimulated gene (ISG). Suprisingly, we unveil that several viruses, including SARS-CoV-2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of Slc29a3 expression is sufficient to significantly decrease viral replication in vitro and in vivo. Our study reveals that ENT3 is a pro-viral ISG co-opted by some viruses to gain a survival advantage.

Equilibrative nucleoside transporter 3 supports microglial functions and protects against the progression of Huntington's disease in the mouse model.

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric symptoms. Currently, there is no cure, and only limited treatments are available to manage the symptoms and to slow down the disease's progression. The molecular and cellular mechanisms of HD's pathogenesis are complex, involving immune cell activation, altered protein turnover, and disturbance in brain energy homeostasis. Microglia have been known to play a dual role in HD, contributing to neurodegeneration through inflammation but also enacting neuroprotective effects by clearing mHTT aggregates. However, little is known about the contribution of microglial metabolism to HD progression. This study explores the impact of a microglial metabolite transporter, equilibrative nucleoside transporter 3 (ENT3), in HD. Known as a lysosomal membrane transporter protein, ENT3 is highly enriched in microglia, with its expression correlated with HD severity. Using the R6/2 ENT3-/- mouse model, we found that the deletion of ENT3 increases microglia numbers yet worsens HD progression, leading to mHTT accumulation, cell death, and disturbed energy metabolism. These results suggest that the delicate balance between microglial metabolism and function is crucial for maintaining brain homeostasis and that ENT3 has a protective role in ameliorating neurodegenerative processes.

LMBD1 protein participates in cell mitosis by regulating microtubule assembly.

LMBD1 was previously demonstrated to regulate the endocytosis of insulin receptor on the cell surface and to mediate the export of cobalamin from the lysosomes to the cytosol, but little is known about its function in mitosis. In this study, interactome analysis data indicate that LMBD1 is involved in cytoskeleton regulation. Both immunoprecipitation and GST pulldown assays demonstrated the association of LMBD1 with tubulin. Immunofluorescence staining also showed the colocalization of LMBD1 with microtubule in both interphase and mitotic cells. LMBD1 specifically accelerates microtubule assembly dynamics in vitro and antagonizes the microtubule-disruptive effect of vinblastine. In addition, LMBRD1-knockdown impairs mitotic spindle formation, inhibits tubulin polymerization, and diminishes the mitosis-associated tubulin acetylation. The reduced acetylation can be reversed by ectopic expression of LMBD1 protein. These results suggest that LMBD1 protein stabilizes microtubule intermediates. Furthermore, embryonic fibroblasts derived from Lmbrd1 heterozygous knockout mice showed abnormality in microtubule formation, mitosis, and cell growth. Taken together, LMBD1 plays a pivotal role in regulating microtubule assembly that is essential for the process of cell mitosis.

HLA-DQ genotype and biochemical characterization of anti-transglutaminase 2 antibodies in patients with type 1 diabetes mellitus in Taiwan.

Human Leukocyte Antigen (HLA)-DQ2 and HLA-DQ8 are genetic risk factors for Type 1 Diabetes Mellitus (T1DM) and Celiac disease (CD) in Caucasians, but their association with Taiwanese Han population is unknown. We screened 532 Taiwanese T1DM patients for CD biomarkers including anti-tissue transglutaminase (TGM2), anti-gliadin and anti-neoepitope antibodies (Abs), sequencing DQB1 genotypes, and characterized the TGM2 Abs. We report that 3.76% of Taiwanese patients had TGM2-Abs and all had no CD's symptoms. In contrast to Caucasian's CD patients, DQ2/DQ8 only constituted ~4/5 of TGM2-Abs positive patients, while the other ~1/5 patients belonged to different HLA genotypes. Either anti-gliadin or anti-neoepitope Abs coexisted with ~3/4 of TGM2-Abs positive patients that were likely due to gluten-ingestion, while the cause of TGM2-Abs production for other ~1/4 of patients was unknown. Purified anti-TGM2 IgA (TGA) and anti-TGM2 IgG (TGG) could bind on endothelial cells surface, recognized native better than denatured forms of TGM2, and TGA inhibited TGM2's transamidation activity by up to 80% but TGG had no effects. Epitope mapping of all TGM2-Abs positive sera demonstrated that TGM2-Abs had heterogeneity in specificities. This is the first study on the differences between Taiwanese Han group and Caucasian in HLA genotypes and properties of TGM2-Abs.

Mesorhizobium composti sp. nov., isolated from compost.

A polyphasic taxonomic approach was used to characterize a presumptively novel diazotrophic bacterium, designated strain CC-YTH430T, isolated from a compost sample in Taiwan. Cells of strain CC-YTH430T were found to be Gram-stain negative, facultative anaerobic rods that formed yellow-colored colonies on nutrient agar. Cell growth occurred at 15-40 °C, pH 5.0-9.0 and in the presence of 0-2% NaCl. Strain CC-YTH430T resembled Mesorhizobium species while sharing high pair-wise 16S rRNA gene sequence similarities with Mesorhizobium silamurunense, Mesorhizobium thiogangeticum, Mesorhizobium plurifarium, Mesorhizobium tamadayense, Mesorhizobium amorphae (96.9% each), Mesorhizobium sediminum (96.8%), and Mesorhizobium soli (96.5%) and < 96.5% similarity to other species. Strain CC-YTH430T showed 78.8-79.7% average nucleotide identity compared to the type strains of M. amorphae, M. plurifarium, M. soli, M. tamadayense and M. wenxiniae. The N2-fixing activity of strain CC-YTH430T was 0.2 nmol ethylene h-1 at 30 °C. The respiratory system was ubiquinone 10 (Q-10) and the DNA G+C content was 62.0 ± 0.2 mol%. The major fatty acids (> 5%) were C16:0, C17:0 cyclo, C19:0 cyclo ω8c, C14:0 3OH/C16:1 iso I and C18:1ω7c/C18:1ω6c. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine and an unidentified aminolipid in major amounts. In addition, phosphatidylethanolamine, an unidentified lipid and several unidentified polar lipids were also found in moderate-to-trace amounts. Based on the phylogenetic, phenotypic and chemotaxonomic features, strain CC-YTH430T is proposed to represent a novel Mesorhizobium species, for which the name Mesorhizobium composti sp. nov. (type strain CC-YTH430T = BCRC 81024T = JCM 31762T) is proposed.

Castellaniella fermenti sp. nov., isolated from a fermented meal.

A polyphasic taxonomic approach was used to characterize a presumably novel bacterium, designated strain CC-YTH191T, isolated from a fermented meal in Taiwan. Cells of strain CC-YTH191T were Gram-stain-negative aerobic rods, which grew at 15-40 °C (optimal 25-30 °C), pH 6.0-9.0 (optimal 7.0) and 1-2 % (w/v) NaCl (optimal 1 %). On the basis of 16S rRNA gene sequence analysis, strain CC-YTH191T appeared to belong to the genus Castellaniella, and was closely related to Castellaniella hirudinis (96.7 % similarity), Castellaniella ginsengisoli (96.7 %) and Castellaniella caeni (96.0 %), while with other related species it shared <96.0 % similarity. The major cellular fatty acids of the isolate were C16 : 0, C17 : 0cyclo, C14 : 0 3OH/C16 : 1iso I and C18 : 1ω7c/C18 : 1ω6c. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine, three unidentified phospholipids, an unidentified aminolipid and an unidentified aminophospholpid. Putrescine was the predominant polyamine followed by spermidine. The DNA G+C content was 62.2 mol% and the predominant quinone system was ubiquinone 8 (Q-8). All these features confirmed the placement of the strain CC-YTH191T as a novel species within the genus Castellaniella, for which the name Castellaniella fermenti sp. nov. is proposed. The type strain is CC-YTH191T (=BCRC 81023T=JCM 31755T).

Humibacter aquilariae sp. nov., an actinobacterium isolated from an agarwood chip.

A polyphasic taxonomic approach was used to characterize a presumably novel bacterium, designated strain CC-YTH161T, isolated from an agarwood sample. Cells of strain CC-YTH161T were Gram-stain-positive aerobic rods, which grew at 20-40 °C, at pH 5.0-9.0 and with 0-5 % (w/v) NaCl. On the basis of 16S rRNA gene sequence analysis, strain CC-YTH161T appeared to belong to the genus Humibacter, and was closely related to Humibacter antri D7-27T (96.6 % similarity) and Humibacter ginsengiterrae DCY60T (96.2 %). The DNA G+C content was 67.0 mol% and the predominant quinone system was menaquinones (MK) 11 and 12. The major cellular fatty acids of the isolate were C15 : 0, iso-C16 : 0, anteiso-C17 : 0 and C18 : 1ω7c/C18 : 1ω6c. The polar lipid profile comprised predominant amounts of diphosphatidylglycerol followed by two unidentified co-migrating glycolipids and phosphatidylglycerol in significant amounts. The diagnostic diamino acid was 2,4-diaminobutyric acid. All these features confirmed the placement of strain CC-YTH161T within the genus Humibacter. On the basis of evidence from this study, strain CC-YTH161T is considered to represent a novel species of the genus Humibacter, for which the name Humibacter aquilariae sp. nov. is proposed. The type strain is CC-YTH161T (=BCRC 80936T=JCM 31199T).

Chryseobacterium endophyticum sp. nov., isolated from a maize leaf.

A Gram-stain-negative, aerobic, yellow-pigmented, flexirubin-producing, rod-shaped and endophytic bacterium, designated strain CC-YTH209T, was isolated from a maize leaf and subjected to a taxonomic study. Strain CC-YTH209T was found to grow at 15-40 °C (optimal 30 °C), at pH 6.0-8.0 (optimal pH 7.0) and in the presence of 0-2 % (optimal 1 %) (w/v) NaCl. On the basis of 16S rRNA gene sequence analysis, strain CC-YTH209T appeared to belong to the genus Chryseobacterium within the class Flavobacteriia, and was closely related to Chryseobacterium rigui CJ16T (97.5 % similarity) and Chryseobacterium taeanense PHA3-4T (96.9 %). The level of DNA-DNA relatedness between strain CC-YTH209T and Chryseobacterium rigui CJ16T was 14.4 % (reciprocal, 13.0 %). Phylogenetic analyses based on 16S rRNA genes revealed a distinct taxonomic position attained by strain CC-YTH209T within the clade that accommodated Chryseobacterium species. The DNA G+C content was 37.2 mol%. Strain CC-YTH209T contained menaquinone MK-6 as the predominant respiratory quinone and sym-homospermidine as the major polyamine. The major cellular fatty acids of the isolate were iso-C15 : 0, iso-C17 : 0 3-OH and C16 : 1ω6c/C16 : 1ω7c. The polar lipid profile comprised phosphatidylethanolamine and five aminolipids, three lipids, one glycolipid, one aminophospholipid and one phospholipid, which are presently uncharacterized. On the basis of evidence presented in this study, strain CC-YTH209T is considered to represent a novel species of the genus Chryseobacterium, for which the name Chryseobacterium endophyticum sp. nov. is proposed. The type strain is CC-YTH209T (=BCRC 80938T=JCM 31226T).

Effect of swelling of a photoresist on electromagnetic resonance of terahertz metamaterials.

This work uses isopropyl alcohol (IPA) to develop a photoresist. IPA dissolves the photoresist that is not exposed to UV light, and swells the photoresist that is exposed to UV light. The swelling of the photoresist distorts the split-ring resonators (SRRs). The distorted SRRs have a larger loop length, smaller line width, and smaller split gap than undistorted SRRs. The change in the dimensions of the SRRs is caused by the extension of the SRR arms in their longitudinal directions. The resonance frequency of the distorted SRRs is smaller than that of the undistorted SRRs, and the resonance frequency decreases with the development time. The resonance frequency of the distorted SRRs depends on not only their dimensions, but also the bending of their arms. The distorted SRRs in this work have a frequency tuning range with a maximum width of 0.13 THz. The method that is proposed herein uses IPA to fabricate passively tunable terahertz metamaterials, which exhibit the advantages of high reliability, low cost, and ease of fabrication.

Protein-bound uremic toxins induce tissue remodeling by targeting the EGF receptor.

Indoxyl sulfate and p-cresol sulfate have been suggested to induce kidney tissue remodeling. This study aimed to clarify the molecular mechanisms underlying this tissue remodeling using cultured human proximal renal tubular cells and half-nephrectomized mice treated with indoxyl sulfate or p-cresol sulfate as study models. Molecular docking results suggested that indoxyl sulfate and p-cresol sulfate dock on a putative interdomain pocket of the extracellular EGF receptor. In vitro spectrophotometric analysis revealed that the presence of a synthetic EGF receptor peptide significantly decreased the spectrophotometric absorption of indoxyl sulfate and p-cresol sulfate. In cultured cells, indoxyl sulfate and p-cresol sulfate activated the EGF receptor and downstream signaling by enhancing receptor dimerization, and increased expression of matrix metalloproteinases 2 and 9 in an EGF receptor-dependent manner. Treatment of mice with indoxyl sulfate or p-cresol sulfate significantly activated the renal EGF receptor and increased the tubulointerstitial expression of matrix metalloproteinases 2 and 9. In conclusion, indoxyl sulfate and p-cresol sulfate may induce kidney tissue remodeling through direct binding and activation of the renal EGF receptor.

Differential roles of serotonin receptor subtypes in regulation of neurotrophin receptor expression and intestinal hypernociception.

OBJECTIVES: Aberrant serotonin (5-hydroxytryptamine, 5-HT) metabolism and neurite outgrowth were associated with abdominal pain in irritable bowel syndrome (IBS). We previously demonstrated that 5-HT receptor subtype 7 (5-HT7) was involved in visceral hypersensitivity of IBS-like mouse models. The aim was to compare the analgesic effects of a novel 5-HT7 antagonist to reference standards in mouse models and investigate the mechanisms of 5-HT7-dependent neuroplasticity. METHODS: Two mouse models, including Giardia post-infection combined with water avoidance stress (GW) and post-resolution of trinitrobenzene sulfonic acid-induced colitis (PT) were used. Mice were orally administered CYY1005 (CYY, a novel 5-HT7 antagonist), alosetron (ALN, a 5-HT3 antagonist), and loperamide (LPM, an opioid receptor agonist) prior to measurement of visceromotor responses (VMR). Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin receptors (NTRs) were assessed. RESULTS: Peroral CYY was more potent than ALN or LPM in reducing VMR values in GW and PT mice. Increased mucosal 5-HT7-expressing nerve fibers were associated with elevated Gap43 levels in the mouse colon. We observed higher colonic Ntrk2 and Ngfr expression in GW mice, and increased Bdnf expression in PT mice compared with control mice. Human SH-SY5Y cells stimulated with mouse colonic supernatant or exogenous serotonin exhibited longer nerve fibers, which CYY dose-dependently inhibited. Serotonin increased Ntrk1 and Ngfr expression via 5-HT7 but not 5-HT3 or 5-HT4, while Ntrk2 upregulation was dependent on all three 5-HT receptor subtypes. CONCLUSIONS: Stronger analgesic effects by peroral CYY were observed compared with reference standards in two IBS-like mouse models. The 5-HT7-dependent NTR upregulation and neurite elongation may be involved in intestinal hypernociception.

Predictors for Failed Removal of Nasogastric Tube in Patients With Brain Insult.

OBJECTIVE: To construct a prognostic model for unsuccessful removal of nasogastric tube (NGT) was the aim of our study. METHODS: This study examined patients with swallowing disorders receiving NGT feeding due to stroke or traumatic brain injury in a regional hospital. Clinical data was collected, such as age, sex, body mass index (BMI), level of activities of daily living (ADLs) dependence. Additionally, gather information regarding the enhancement in Functional Oral Intake Scale (FOIS) levels and the increase in food types according to the International Dysphagia Diet Standardization Initiative (IDDSI) after one month of swallowing training. A stepwise logistic regression analysis model was employed to predict NGT removal failure using these parameters. RESULTS: Out of 203 patients, 53 patients (26.1%) had experienced a failed removal of NGT after six months of follow-up. The strongest predictors for failed removal were age over 60 years, underweight BMI, total dependence in ADLs, and ischemic stroke. The admission prediction model categorized patients into high, moderate, and low-risk groups for removal failure. The failure rate of NGT removal was high not only in the high-risk group but also in the moderate-risk groups when there was no improvement in FOIS levels and IDDSI food types. CONCLUSION: Our predictive model categorizes patients with brain insults into risk groups for swallowing disorders, enabling advanced interventions such as percutaneous endoscopic gastrostomy for high-risk patients struggling with NGT removal, while follow-up assessments using FOIS and IDDSI aid in guiding rehabilitation decisions for those at moderate risk.

Unraveling the Link between Periodontitis and Coronavirus Disease 2019: Exploring Pathogenic Pathways and Clinical Implications.

Periodontitis involves the inflammation of the periodontal tissue, leading to tissue loss, while coronavirus disease 2019 (COVID-19) is a highly transmissible respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is amplified by poor systemic health. Key facilitators of SARS-CoV-2's entry into host cells are angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). This review reveals that periodontal pockets can serve as a hotspot for virus accumulation, rendering surrounding epithelia more susceptible to infection. Given that ACE2 is expressed in oral mucosa, it is reasonable to suggest that poor periodontal health could increase the risk of COVID-19 infection. However, recent studies have not provided sufficient evidence to imply a significant effect of COVID-19 on periodontal health, necessitating further and more long-term investigations. Nevertheless, there are hypotheses linking the mechanisms of the two diseases, such as the involvement of interleukin-17 (IL-17). Elevated IL-17 levels are observed in both COVID-19 and periodontitis, leading to increased osteoclast activity and bone resorption. Lastly, bidirectional relationships between periodontitis and systemic diseases like diabetes are acknowledged. Given that COVID-19 symptoms may worsen with these conditions, maintaining good oral health and managing systemic diseases are suggested as potential ways to protect against COVID-19.

Automatic disulfide bond assignment using a1 ion screening by mass spectrometry for structural characterization of protein pharmaceuticals.

An automatic method for disulfide bond assignment using dimethyl labeling and computational screening of a(1) ions with customized software, RADAR, is developed. By utilization of the enhanced a(1) ions generated from labeled peptides, the N-terminal amino acids from disulfide-linked peptides can be determined. In this study, we applied this method for structural characterization of recombinant monoclonal antibodies, an important group of therapeutic proteins. In addition to a(1) ion screening and molecular weight match, new RADAR is capable of confirming the matched peptide pairs by further comparing the collision-induced dissociation (CID) fragment ions. With the N-terminal amino acid identities as a threshold, the identification of disulfide-linked peptide pairs can be achieved rapidly at a higher confidence level. Unlike most current approaches, prior knowledge of disulfide linkages or a high-end mass spectrometer is not required, and tedious work or deliberate interpretation can be avoided in this study. Our approach makes it possible to analyze unknown disulfide bonds of protein pharmaceuticals as well as their degraded forms without further protein separation. It can be used as a convenient quality examination tool during biopharmaceutical development and manufacturing processes.

Multiomics reveal the central role of pentose phosphate pathway in resident thymic macrophages to cope with efferocytosis-associated stress.

Tissue-resident macrophages (TRMs) are heterogeneous cell populations found throughout the body. Depending on their location, they perform diverse functions maintaining tissue homeostasis and providing immune surveillance. To survive and function within, TRMs adapt metabolically to the distinct microenvironments. However, little is known about the metabolic signatures of TRMs. The thymus provides a nurturing milieu for developing thymocytes yet efficiently removes those that fail the selection, relying on the resident thymic macrophages (TMφs). This study harnesses multiomics analyses to characterize TMφs and unveils their metabolic features. We find that the pentose phosphate pathway (PPP) is preferentially activated in TMφs, responding to the reduction-oxidation demands associated with the efferocytosis of dying thymocytes. The blockade of PPP in Mφs leads to decreased efferocytosis, which can be rescued by reactive oxygen species (ROS) scavengers. Our study reveals the key role of the PPP in TMφs and underscores the importance of metabolic adaptation in supporting Mφ efferocytosis.

High Tumor Burden Predicts Poor Response to Enzalutamide in Metastatic Castration-Resistant Prostate Cancer Patients.

To assess the predictive value of tumor burden on the biochemical response, and radiological response in Taiwanese metastatic castration-resistant prostate cancer (mCRPC) patients receiving enzalutamide. The mCRPC patients treated with enzalutamide were recruited from three hospitals. High tumor burden (HTB) was classified as metastases at either appendicular bone or visceral organ. Good prostate-specific antigen (PSA) response was defined as PSA reduction of 80%. In this cohort, there were 104 (54.2%) HTB patients and 88 (45.8%) with low tumor burden (LTB). Compared to LTB patients, fewer HTB patients had good PSA response (odds ratio: 0.43, range: 0.22-0.87, p = 0.019) and fewer radiological response (complete and partial remission) (odds ratio: 0.78, range: 0.36-1.68, p = 0.52) to enzalutamide. The disease control rate which also contained stable disease, was still lower in HTB (76.0%) than LTB group (92.9%, OR: 0.24, range: 0.07-0.77, p = 0.016) in the multivariable model. In addition, HTB patients had significantly shorter progression-free survival duration than did LTB patients (median: 8.3 vs. 21.6 months, log-rank test p = 0.003) in the univariable analysis. The tumor burden before the use of enzalutamide was associated with treatment outcomes. HTB reduced PSA response rate, radiological response rate and progression-free survival duration.

A Pilot Study of Two Different Constraint-Induced Movement Therapy Interventions in Children With Hemiplegic Cerebral Palsy After Botulinum Toxin Injection During Preschool Education.

Introduction: To establish a pilot study on applying two low dose (40 h) constraint-induced movement therapy (CIMT) interventions in children with hemiplegic cerebral palsy (CP) after botulinum toxin (BoNT-A) injection during preschool education. Methods: Five children with spastic CP (mean age: 5.31 years; Gross Motor Function Classification System level I and II) undergoing regular BoNT-A injections and rehabilitation programs were included. Participants were randomly allocated to one of two CIMT programs (40 h): a 2-week 4-hours/day CIMT program and a 4-week 2-hours/day CIMT program. One CIMT program was performed 1 month after a BoNT-A injection, and then the second program was implemented with the next injection. The outcomes were measured by changes in Goal Attainment Scaling (GAS), the grasp and Visual-Motor Integration (VMI) test in Peabody-Developmental Motor Scales (PDMS), the self-care scale on the Functional Skill Scale, and the Caregiver Assistance in Chinese Version of Pediatric Evaluation of Disability Inventory (PEDI-C), Anxiety and Oppositional Defiance Problems of Achenbach System of Empirically-Based Assessment before and after the CIMT interventions, and at every 2 months' follow-up thereafter. Results: The mean age of the participants was 5.31 years, BMI was 16.7 (kg/m2), VIQ was 86.4 ± 8.5, and dose of BoNT-A injection in the upper limb was 42 ± 26.6 units. Grasp, VMI, and self-care on the Functional Skill Scale were significantly better in the 4-week 2-hours/day CIMT program (p < 0.001, p = 0.001, p < 0.001). GAS, grasp, VMI, two 2 self-care scales of PEDI were significantly improved after the CIMT programs, and improvement continued for up to 4 months after the programs. There was no clinical evidence showing changes in the scores for anxiety and oppositional defiance problems during the study period. Conclusions: The preliminary findings, although limited, suggest a potential therapeutic role for the school-based CIMT program after BoNT-A injection. The 4-week 2-hours/day CIMT program might be better than a 2-week 4-hours/day program in terms of self-care and hand function when performed in kindergarten in this pilot study. Furthermore, this pilot study provides valuable information; therefore, it is crucial to include more CP children and blinded assessors for hand function and ADL in the future study.

Clinical association between the metabolite of healthy gut microbiota, 3-indolepropionic acid and chronic kidney disease.

BACKGROUND & AIMS: Emerging evidence indicates that gut microbiota serves an important role in the development and progression of chronic kidney disease (CKD). Changes to the gut microbial flora can cause the generation of uremic toxins, which contribute to chronic kidney injury. The aim of the current study was to explore the clinical association between metabolites and CKD. METHODS: Between August 2013 and January 2015, a two-phase case-control study was conducted to analyze the clinical association between metabolites and CKD in a community health program. The first phase of the study was a prospective case-control survey designed for comparing the differences in the metabolome profile of patients with (n = 10) and without (n = 10) estimated glomerular filtration rate (eGFR) rapid decline (a yearly decline >20%). The second phase of the study was a cross-sectional case-control study, which checked and compared the metabolites, indoxyl sulfate and p-cresol sulfate levels between healthy subjects (n = 144) and CKD patients (n = 140). RESULTS: In the first phase of the study, it was revealed that IPA levels of patients with rapid renal function decline were significantly reduced compared with the control patients (n = 10 for each group). The second phase furthered checked and compared the IPA, indoxyl sulfate and p-cresol sulfate levels between healthy subjects (n = 144) and CKD patients (n = 140). The results showed that the average level of indoxyl sulfate (2738.2 vs. 541.0 ng/ml, P < 0.01) and p-cresol sulfate (1442.8 vs. 1394.6 ng/ml, P < 0.01) were significantly higher in the CKD patients, while the average level of IPA was significantly higher (49.8 vs. 34.7 ng/ml, P < 0.01) in the control patients. CONCLUSIONS: Our results suggest that IPA might be an important biomarker and renal protector against the development of CKD.

Acupuncture for a first episode of acute ischaemic stroke: an observer-blinded randomised controlled pilot study.

OBJECTIVE: To determine the required sample size for, and feasibility of, a RCT examining the effectiveness of early acupuncture for acute ischaemic stroke. METHODS: Thirty-eight patients aged 40-85 years with a first episode of acute ischaemic stroke presenting within 72 h of stroke onset were randomly assigned to receive manual acupuncture (MA group; n=20) plus standard care or standard care only (control group, n=18). The acupuncture treatment was provided daily for 2 weeks. The primary outcome was the change in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and 4 weeks. Secondary outcomes included changes in the Fugl-Meyer assessment (FMA) and the functional independence measure scores between baseline and 4 weeks, and changes in NIHSS, Barthel Index and modified Rankin Scale scores at 12 weeks. RESULTS: Thirty-one patients completed the study (dropout rate=18%) and adverse effects were minimal. No significant differences were seen between groups in the improvements in NIHSS scores, although there tended to be a greater reduction in NIHSS score after 1 week in the MA group relative to the control group (p=0.066). The post-stroke motor activity at 4 weeks was associated with a significantly increased FMA score in the acupuncture group compared with the control group (p<0.05), but not supported by intergroup analysis. CONCLUSIONS: This pilot study indicates that acupuncture appears to be safe for patients in the acute stage of ischaemic stroke. A subsequent trial with a larger sample size (estimated at n=122) is required to confirm whether early acupuncture intervention contributes to earlier functional improvement and to assess the longer-term clinical efficacy of acupuncture. TRIAL REGISTRATION NUMBER: NCT02210988; Results.