Co-condensation between transcription factor and coactivator p300 modulates transcriptional bursting kinetics.

The coactivator p300/CREB-binding protein (CBP) regulates genes by facilitating the assembly of transcriptional machinery and by acetylating histones and other factors. However, it remains mostly unclear how both functions of p300 are dynamically coordinated during gene control. Here, we showed that p300 can orchestrate two functions through the formation of dynamic clusters with certain transcription factors (TFs), which is mediated by the interactions between a TF's transactivation domain (TAD) and the intrinsically disordered regions of p300. Co-condensation can enable spatially defined, all-or-none activation of p300's catalytic activity, priming the recruitment of coactivators, including Brd4. We showed that co-condensation can modulate transcriptional initiation rate and burst duration of target genes, underlying nonlinear gene regulatory functions. Such modulation is consistent with how p300 might shape gene bursting kinetics globally. Altogether, these results suggest an intriguing gene regulation mechanism, in which TF and p300 co-condensation contributes to transcriptional bursting regulation and cooperative gene control.

Omicron BA.4/5 neutralization and cell-mediated immune responses in relation to baseline immune status and breakthrough infection among PLWH: A follow-up cohort study.

There is a paucity of data on hybrid immunity (vaccination plus breakthrough infection [BI]), especially cell-mediated responses to Omicron among immunosuppressed patients. We aim to investigate humoral and cellular responses to Omicron BA.4/5 among people living with HIV (PLWH) with/without BIs, the most prevalent variant of concern after the reopening of China. Based on our previous study, we enrolled 77 PLWH with baseline immune status of severe acute respiratory syndrome coronavirus 2 specific antibodies after inactivated vaccination. "Correlates of protection," including serological immunoassays, T cell phenotypes and memory B cells (MBC) were determined in PLWH without and with BI, together with 16 PLWH with reinfections. Higher inhibition rate of neutralizing antibodies (NAb) against BA.4/5 was elicited among PLWH with BI than those without. Omicron-reactive IL4+ CD8+ T cells were significantly elevated in PLWH experienced postvaccine infection contrasting with those did not. NAb towards wild type at baseline was associated with prolonged negative conversion time for PLWH whereas intermediate MBCs serve as protecting effectors. We uncovered that hybrid immunity intensified more protection on BA.4/5 than vaccination did. Strengthened surveillance on immunological parameters and timely clinical intervention on PLWH deficient in protection would reduce the severity and mortality in the context of coexistence with new Omicron subvariants.

PFKFB3-driven vascular smooth muscle cell glycolysis promotes vascular calcification via the altered FoxO3 and lactate production.

A link between increased glycolysis and vascular calcification has recently been reported, but it remains unclear how increased glycolysis contributes to vascular calcification. We therefore investigated the role of PFKFB3, a critical enzyme of glycolysis, in vascular calcification. We found that PFKFB3 expression was upregulated in calcified mouse VSMCs and arteries. We showed that expression of miR-26a-5p and miR-26b-5p in calcified mouse arteries was significantly decreased, and a negative correlation between Pfkfb3 mRNA expression and miR-26a-5p or miR-26b-5p was seen in these samples. Overexpression of miR-26a/b-5p significantly inhibited PFKFB3 expression in VSMCs. Intriguingly, pharmacological inhibition of PFKFB3 using PFK15 or knockdown of PFKFB3 ameliorated vascular calcification in vD3 -overloaded mice in vivo or attenuated high phosphate (Pi)-induced VSMC calcification in vitro. Consistently, knockdown of PFKFB3 significantly reduced glycolysis and osteogenic transdifferentiation of VSMCs, whereas overexpression of PFKFB3 in VSMCs induced the opposite effects. RNA-seq analysis and subsequent experiments revealed that silencing of PFKFB3 inhibited FoxO3 expression in VSMCs. Silencing of FoxO3 phenocopied the effects of PFKFB3 depletion on Ocn and Opg expression but not Alpl in VSMCs. Pyruvate or lactate supplementation, the product of glycolysis, reversed the PFKFB3 depletion-mediated effects on ALP activity and OPG protein expression in VSMCs. Our results reveal that blockade of PFKFB3-mediated glycolysis inhibits vascular calcification in vitro and in vivo. Mechanistically, we show that FoxO3 and lactate production are involved in PFKFB3-driven osteogenic transdifferentiation of VSMCs. PFKFB3 may be a promising therapeutic target for the treatment of vascular calcification.

Hydrogel dressings for diabetic foot ulcer: A systematic review and meta-analysis.

AIM: To investigate the differences in utility between conventional dressings and hydrogel dressings for the treatment of diabetic foot ulcer (DFU). METHODS: The PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases were systematically searched up to 21 January 2023. Fixed/random-effect models were used to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) for the effect size analysis, with heterogeneity determined by I2 statistics. Subgroup analyses of different classes of hydrogel were also conducted. RESULTS: A total of 15 randomized controlled trials with 872 patients were eligible for the present analysis. Compared with conventional dressings, hydrogel dressings significantly improved the healing rate (OR 4.09, 95% CI 2.83 to 5.91), shortened the healing time (MD -11.38, 95% CI -13.11 to -9.66), enhanced granulation formation (MD -3.60, 95% CI -4.21 to -3.00) and epithelial formation (MD -2.82, 95% CI -3.19 to -2.46), and reduced the incidence of bacterial infection (OR 0.10, 95% CI 0.05 to 0.18). CONCLUSION: The meta-analysis showed that hydrogel dressings are more effective in treating DFU compared with conventional dressings.

The intra-S phase checkpoint directly regulates replication elongation to preserve the integrity of stalled replisomes.

DNA replication is dramatically slowed down under replication stress. The regulation of replication speed is a conserved response in eukaryotes and, in fission yeast, requires the checkpoint kinases Rad3ATR and Cds1Chk2 However, the underlying mechanism of this checkpoint regulation remains unresolved. Here, we report that the Rad3ATR-Cds1Chk2 checkpoint directly targets the Cdc45-MCM-GINS (CMG) replicative helicase under replication stress. When replication forks stall, the Cds1Chk2 kinase directly phosphorylates Cdc45 on the S275, S322, and S397 residues, which significantly reduces CMG helicase activity. Furthermore, in cds1Chk2 -mutated cells, the CMG helicase and DNA polymerases are physically separated, potentially disrupting replisomes and collapsing replication forks. This study demonstrates that the intra-S phase checkpoint directly regulates replication elongation, reduces CMG helicase processivity, prevents CMG helicase delinking from DNA polymerases, and therefore helps preserve the integrity of stalled replisomes and replication forks.

Visualization of the relationship between macrophage and wound healing from the perspective of bibliometric analysis.

Macrophages play a crucial role in aiding all phases of the wound-healing process and has garnered increasing attention recently. Although a substantial body of related studies has been published, there remains a lack of comprehensive bibliometric analysis. In this study, we collected 4296 papers from the Web of Science Core Collection database. Three tools including CiteSpace, VOSviewer and one online analytical platform were employed to conduct bibliometric analysis and data visualization. Our results revealed that the annual number of publications related to macrophage and wound healing has increased exponentially with the year. The United States and China stand as the primary driving forces within this field, collectively constituting 58.2% of the total publication output. The application of biomaterials was one of the most concerned research areas in this field. According to references analysis, the current research focus has shifted to diabetic wound healing and regulating macrophage polarization. Based on the keywords analysis, we identified the following research frontiers in the future: exosomes and other extracellular vesicles; bio-derived materials and drug delivery methods such as nanoparticles, scaffolds and hydrogels; immunomodulation and macrophage polarization in the M2-state; chronic wounds, particularly those associated with diabetes; antimicrobial peptides; and antioxidant. Additionally, TNF, IL-6, IL-10, TGF-ß1 and VEGF ranked as the five genes that have garnered the most research attention in the intersection of macrophage and wound healing. All in all, our findings offered researchers a holistic view of the ongoing progress in the field of macrophages and wound healing, serving as a valuable reference for scholars and policymakers in this domain.

Advances in isothermal nucleic acid amplification methods for hepatitis B virus detection.

Hepatitis B virus (HBV) infection is a major global health problem of widespread concern. Clinically, serological assays are the most widely used diagnostic tests for HBV infection, with the presence of HBsAg in the serum being indicative of acute and chronic hepatitis B infection. However, increased identification of HBV DNA positive but HBsAg negative cases has greatly promoted the use of molecular assays for more accurate HBV diagnosis. Over the past few decades, especially since the outbreak of COVID-19, significant advancements have been made in the techniques and devices for nucleic acid testing (NAT). Nowadays, the mainstream NAT techniques can broadly be split into two categories: PCR-based methods and non-PCR-based isothermal amplification methods. As achieving point-of-care testing (POCT) or on-site testing is an important development tendency for the next-generation NAT, non-PCR-based isothermal amplification methods like nucleic acid sequence-based amplification (NASBA), rolling circle amplification (RCA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), and recombinase polymerase amplification (RPA) have garnered significant attention in recent years. In this review, we provide a comprehensive overview of the nucleic acid isothermal amplification technologies currently used for HBV detection. The analytical performances of different methods are compared and their integration with microfluidics, lateral flow assays, and CRISPR/Cas systems is also discussed.

Metabolic RNA labeling for probing RNA dynamics in bacteria.

Metabolic labeling of RNAs with noncanonical nucleosides that are chemically active, followed by chemoselective conjugation with imaging probes or enrichment tags, has emerged as a powerful method for studying RNA transcription and degradation in eukaryotes. However, metabolic RNA labeling is not applicable for prokaryotes, in which the complexity and distinctness of gene regulation largely remain to be explored. Here, we report 2'-deoxy-2'-azidoguanosine (AzG) as a noncanonical nucleoside compatible with metabolic labeling of bacterial RNAs. With AzG, we develop AIR-seq (azidonucleoside-incorporated RNA sequencing), which enables genome-wide analysis of transcription upon heat stress in Escherichia coli. Furthermore, AIR-seq coupled with pulse-chase labeling allows for global analysis of bacterial RNA degradation. Finally, we demonstrate that RNAs of mouse gut microbiotas can be metabolically labeled with AzG in living animals. The AzG-enabled metabolic RNA labeling should find broad applications in studying RNA biology in various bacterial species.

Morphological specificity analysis of an image-based 3D model of airway filling in a difficult airway.

BACKGROUND: The purpose of this study was to analyze position-specific morphological changes of the upper airway and to further assess the impact of these changes in difficult airway during intubation. METHODS: This observational comparative study included two groups (n = 20 patients/group): Group A had normal airway and Group B had difficult airway. Data obtained from two-dimensional magnetic resonance imaging were imported to Mimics V20.0 software for processing. We then reconstructed three-dimensional models of upper airway filling in patients in the supine and maximum extension position based on the imaging data. Those models were projected on coronal, sagittal, and horizontal planes to investigate multiple morphological features. We measured the surface area, radial length, and corner angle of the projected areas. RESULTS: Group A had larger upper airway filling volumes compared to Group B The volumes for the supine position were 6,323.83 ± 156.06 mm3 for Group A and 5,336.22 ± 316.13 mm3 for Group B (p = 0.003). The volumes the maximum extension position were 9,186.58 ± 512.61 mm3 for Group A and 6,735.46 ± 794.63 mm3 for Group B (p = 0.003). Airway volume increased in the upper airway filling model as the body position varied from the supine to maximum extension position (Group A: volume increase 2,953.75 ± 524.6 mm3, rate of change 31%; Group B: volume increase 1,632.89 ± 662.66 mm3, rate of change 25%; p = 0.052). CONCLUSION: The three-dimensional reconstruction model developed in this study was used to digitally quantify morphological features of a difficult airway and could be used as a novel airway management assessment tool.

[Tanshinone IIa attenuates vascular calcification through inhibition of NF-κB and ß-catenin signaling pathways].

Tanshinone IIa is a key ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza (Danshen), and is widely used to treat various cardiovascular diseases. Vascular calcification is a common pathological change of cardiovascular tissues in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. However, whether Tanshinone IIa inhibits vascular calcification and the underlying mechanisms remain largely unknown. This study aims to investigate whether Tanshinone IIa can inhibit vascular calcification using high phosphate-induced vascular smooth muscle cell and aortic ring calcification model, and high dose vitamin D3 (vD3)-induced mouse models of vascular calcification. Alizarin red staining and calcium quantitative assay showed that Tanshinone IIa significantly inhibited high phosphate-induced vascular smooth muscle cell and aortic ring calcification. qPCR and Western blot showed that Tanshinone IIa attenuated the osteogenic transition of vascular smooth muscle cells. In addition, Tanshinone IIa also significantly inhibited high dose vD3-induced mouse aortic calcification and aortic osteogenic transition. Mechanistically, Tanshinone IIa inhibited the activation of NF-κB and ß-catenin signaling in normal vascular smooth muscle cells. Similar to Tanshinone IIa, inhibition of NF-κB and ß-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification. These results suggest that Tanshinone IIa attenuates vascular calcification at least in part through inhibition of NF-κB and ß-catenin signaling, and Tanshinone IIa may be a potential drug for the treatment of vascular calcification.

Age differences in Neural Activation to Face Trustworthiness: Voxel Pattern and Activation Level Assessments.

Judgment of trustworthiness is an important social ability. Many studies show neural activation differences to variations in face trustworthiness in brain reward regions. A previously published analysis of the present fMRI data showed that older adults' (OA) reward region activation responded significantly to trustworthiness in a set of older and younger faces, whereas younger adults' (YA) activation did not-a finding inconsistent with studies that used only younger faces. We hypothesized that voxel pattern analyses would be more sensitive to YA neural responses to trustworthiness in our set of faces, replicating YA neural discrimination in prior literature. Based on evidence for OA neural dedifferentiation, we also hypothesized that voxel pattern analyses would more accurately classify YA than OA neural responses to face trustworthiness. We reanalyzed the data with two pattern classification models and evaluated the models' performance with permutation testing. Voxel patterns discriminated face trustworthiness levels in both YA and OA reward regions, while allowing better classification of face trustworthiness for YA than OA, the reverse of previous results for neural activation levels. The moderation of age differences by analytic method shines a light on the possibility that voxel patterns uniquely index neural representations of the stimulus information content, consistent with findings of impaired representation with age.

Assessment of Liver Fibrosis Using Real-time Shear-wave Elastography for Patients with Hepatitis B e Antigen-negative Chronic Hepatitis B and Alanine Transaminase <2 Times the Upper Limit of Normal.

BACKGROUND: We assessed liver fibrosis using real-time shear-wave elastography (SWE) combined with liver biopsy (LB) for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) and alanine transaminase < 2 times the upper limit of normal and hepatitis B virus DNA < 2000 IU/ml. METHODS: A total of 107 patients met the inclusion criteria. Real- ime SWE and ultrasoundassisted liver biopsies were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic curve were performed to calculate the optimal area under the receiver operating characteristic curve for F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4 for real-time SWE. RESULTS: The most concurrent liver fibrosis degrees were between F1 and F2 for these HBeAg-negative CHB patients. Liver stiffness increased in parallel with the degree of liver fibrosis using SWE measurements. The area under the receiver operating characteristic curves was 0.881 (95% confidence interval [CI]: 0.704-1.000) for SWE (p = 0.004); 0.912 (95% CI: 0.836-0.987) for SWE (p = 0.000); 0.981 (95% CI: 0.956-1.000) for SWE (p = 0.000); 0.974 (95% CI: 0.936-1.000) for SWE (p = 0.000) when comparing F0 versus F1-F4, F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4, respectively. CONCLUSIONS: SWE has the advantage of providing an image of liver stiffness in real-time. As an alternative to LB, the development of all these noninvasive methods for dynamic evaluation of liver fibrosis will decrease the need for LB, making clinical care safer and more convenient for patients with liver diseases.

Navigating Community-Based Aged Care Services From the Consumer Perspective: A Scoping Review.

BACKGROUND AND OBJECTIVES: The shift to consumer-directed aged care means that older adults need to play a more active role in navigating the complex aged care system for adequate health and social services. Challenges in the navigation process result in unmet needs and difficulty accessing available resources. This scoping review investigates how aged care navigation is conceptualized in literature and interrogates research on the experiences of older adults navigating community-based aged care services with or without support from their informal carers. RESEARCH DESIGN AND METHODS: This review follows the Joanna Briggs Institute methodological guidelines. PubMed, Scopus, and ProQuest were searched for relevant literature published from 2008 to 2021, supplemented by grey literature and manual reference list searching. Data were extracted using a predefined data-extraction table and synthesized with an inductive thematic analysis. RESULTS: The current conceptualization of aged care navigation focuses on the support provided to older adults, rather than actions taken by older adults themselves. Thematic analysis from the included studies (n = 26) revealed shared themes (lack of knowledge, social networks as information providers, complex care systems) among older adults and informal carers; unique challenges faced by older adults (difficulties with technology, waiting game), and informal carers (structural burden) in aged care navigation. DISCUSSION AND IMPLICATIONS: Findings suggest the need to comprehensively assess individual circumstances including social networks and access to informal carers as predictors of successful navigation. Changes that reduce the complexity of the aged care system and improve coordination will relieve the structural burden experienced by consumers.

Potential added value of computed tomography radiomics to multimodal prediction models for benign and malignant breast tumors.

Background: Early diagnosis is crucial to the treatment of breast cancer, but conventional imaging detection is challenging. Radiomics has the potential to improve early diagnostic efficacy in a noninvasive manner. This study examined whether integrating computed tomography (CT) radiomics information based on ultrasound (US) models can improve the efficacy of breast cancer prediction. Methods: We retrospectively analyzed 420 patients with pathologically confirmed benign or malignant breast tumors. Clinical data and examination images were collected, and the population was divided into training (n=294) and validation (n=126) groups at a ratio of 7:3. The region of interest (ROI) was manually segmented along the tumor boundary using MaZda software, and the features of each ROI was extracted. After dimension reduction and screening, the best features were retained. Subsequently, random forest (RF), support vector machines, and K-nearest neighbor classifiers were used to establish prediction models in an US and combined-methods group. Results: Finally, 8 of the 379 features were retained in the US group. Random forest was found to be the best model, and the area under the curve (AUC) of the training and validation groups was 0.90 [95% confidence interval (CI): 0.852-0.942] and 0.85 (95% CI: 0.775-0.930), respectively. Meanwhile, 12 of the 750 features were retained in the combined group. In this regard, random forest proved to be the best model, and the AUC of the training and validation group was 0.95 (95% CI: 0.918-0.981) and 0.92 (95% CI: 0.866-0.969), respectively. The calibration curve showed a good fit of the model. The decision curve showed that the clinical net benefit of the combined group was far greater than that of any single examination, and the prediction model of the combined group exhibited a degree of practical clinical value. Conclusions: The combined model based on US and CT images has potential application value in the prognostic prediction of benign and malignant breast diseases.

Barriers Experienced by Community-Dwelling Older Adults Navigating Formal Care: Evidence From an Australian Population-Based National Survey.

OBJECTIVES: This study aims to identify the relationship between psychosocial factors and unmet needs among community-dwelling older adults who have received or who expect to receive formal home-based aged care services. METHODS: A subsample of the national Survey of Disability, Ageing and Carers was used to examine the prevalence of having any unmet needs among older adults navigating care. We also examined associations between older adults' psychosocial factors and their unmet needs using logistic regression. RESULTS: Regression analyses highlighted that perceived social isolation (OR = 1.62, 95% CI: 1.30-2.01), high/very high psychological distress (OR = 2.11, 95% CI: 1.52-2.93), and occasional assistance from informal support (OR = 1.92, 95% CI: 1.22-3.05) were associated with increased odds of having unmet needs, after adjusting for other covariates. DISCUSSION: Our study suggests that older adults facing psychosocial difficulties or lacking informal support are more likely to encounter barriers in accessing formal care. Future policy should address the psychosocial needs and support networks of older adults.

Genetic assessment of eight zoo populations of golden snub-nosed monkey (Rhinopithecus roxellana) implication to the conservation management of captive populations.

Captive breeding programs play an important role in preserving the genetic diversity of endangered species. It is of utmost importance to conduct genetic assessment for captive populations in order to develop scientific breeding plans and conservation management strategies. Here, we genotyped 10 microsatellite loci and sequenced 368 bp of mitochondrial DNA control region for the golden snub-nosed monkey (Rhinopithecus roxellana) from eight captive populations in China, and compared the genetic indices of captive populations with a wild population. Meanwhile, we performed paternity tests to verify the genealogical records and established genetic lineages. A total of 157 individuals were identified from 161 fecal samples, including 135 captive individuals (approximately 25% of captive individuals in China). Microsatellite analysis showed that the nine populations had moderate levels of genetic diversity, with polymorphism information content (PIC) ranging from 0.43 to 0.542; the genetic diversity of captive populations (average PIC: 0.503) was slightly higher than that of the wild population (PIC: 0.438). The Structure analysis indicated that individuals of the eight captive populations contained two different genetic components. We conducted either single-blind or double-blind paternity testing on 40 offspring of captive individuals and found that five offspring from two zoos (Nanjing Hongshan Forest Zoo and Shanghai Wild Animal Park) showed discrepant kinships from their pedigree records, probably due to the inaccuracies in pedigree records. By constructing genetic pedigrees, inbred offspring were found in Beijing Zoo, Shanghai Zoo, Hangzhou Zoo, and Chengdu Zoo. Analysis based on mitochondrial DNA showed a high level of genetic diversity in the eight captive populations (mean nucleotide diversity: 0.047). However, no nucleotide diversity was found in the wild population. This study conducted a genetic survey for captive golden snub-nosed monkeys and will significantly benefit the genetic conservation management for captive populations in the future.

Scientific knowledge graph and trend analysis of Tuina: A bibliometric analysis.

OBJECTIVES: Tuina is an effective complementary and alternative therapy. However, no bibliometric analysis has explored the global research status and emerging trends of tuina. Therefore, our study aimed to provide a perspective on the current state and frontier trends in the field. DESIGN: Bibliometric analysis SETTING: Tuina-related publications between January 1, 2003, and December 31, 2022, were obtained from the Web of Science Core Collection database. MAIN OUTCOME MEASURES: The knowledge graph software CiteSpace and VOSViewer were used to quantitatively analyse annual trends in annual publication volume, journals, countries, institutions, authors, cited references, and keywords. RESULTS: Overall, 1877 articles were obtained. Consequently, the number of annual publications in tuina gradually increased. China published the most articles (1402 articles, 58.01%), followed by the Chinese Academy of Sciences (110 articles, 2.57%). Original and review articles were the two main types of publications. Photonics Research ranked first (101 articles, 5.38%) as the most influential affiliate and productive journal. These articles come from 8423 authors, among whom Min Fang published the most publications, and Ernst E was co-cited most often. According to the keyword co-occurrence analysis, the new research frontiers were meta-analyses. CONCLUSION: This comprehensive bibliometric study analysed the publications on tuina and presented them visually, revealing new research trends, pivotal points, research hotspots, and frontiers. Prospective strategies and potential directions for further studies were also provided.

Discovery of indole analogues from Periplaneta americana extract and their activities on cell proliferation and recovery of ulcerative colitis in mice.

Background: As an important medicinal insect, Periplaneta americana (PA) has been applied for the treatment of wounds, burns, and ulcers with fewer side effects and a reduced recurrence rate, which provides great potential for developing new drugs based on its active constituents. Materials and methods: The main chromatographic peaks determined by high performance liquid chromatography (HPLC) in the PA concentrated ethanol-extract liquid (PACEL) were separated, purified, and identified by semi-preparative LC, mass spectrum, and 1H NMR spectroscopic analysis. The biological activities of the identified compounds were investigated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method based on in vitro human skin fibroblasts (HSF) and in vivo experiments based on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. Furthermore, RT-qPCR of six genes related to inflammation or intestinal epithelial cell proliferation was employed to investigate the molecular mechanism of the indole analogues recovering UC in mice. Results: Five indole analogues were purified and identified from PACEL, including tryptophan (Trp), tryptamine (pa01), 1,2,3,4-tetrahydrogen-ß-carboline-3-carboxylic acid (pa02), (1S, 3S)-1-methyl-1,2,3,4-tetrahydrogen-ß-carboline-3-carboxylic acid (pa03), and (1R, 3S)-1-methyl-1,2,3,4-tetrahydrogen-ß-carboline-3-carboxylic acid (pa04), among which the pa02 and pa04 were reported in PA for the first time. In vitro and in vivo experiments showed that PACEL, Trp, and pa02 had promoting HSF proliferation activity and intragastric administration of them could alleviate symptoms of weight loss and colon length shortening in the UC mice. Although recovery activity of the compound pa01 on the colon length was not as obvious as other compounds, it showed anti-inflammatory activity in histological analysis. In addition, The RT-qPCR results indicated that the three indole analogues could alleviate DSS-induced intestinal inflammation in mice by inhibiting pro-inflammatory cytokines (MMP7, IL1α) and down-regulating BMP8B expression. Conclusion: This study reported the isolation, purification, structure identification, and biological activity of the active indole analogues in PACEL. It was found for the first time that the PA extract contained many indole analogues and Trp, which exhibited good proliferation activity on HSF fibroblasts as well as anti-UC activity in mice. These indole analogues probably are important components related to the pharmacological activity in PA.

Effects of L-carnitine supplementation on glucolipid metabolism: a systematic review and meta-analysis.

Background: L-carnitine supplementation has been utilized against glucolipid metabolism disruption. However, to the best of our knowledge, no meta-analysis process has analyzed the effects of L-carnitine supplementation on insulin resistance, fasting blood glucose, lipid metabolism, and liver enzyme levels in adults. Methods: Through the analysis and screening of 12 221 studies, 15 studies were selected from eligible trials for meta-analysis. Meta-analysis was performed in a random effect model with heterogeneity determined by I2, and subgroup analyses were used to further identify the source of heterogeneity. Result: The results showed significant effects of L-carnitine on FBG (MD = -4.94 mg dL-1, 95% CI: -7.07 to -2.82), insulin (MD = -0.99 µU mL-1, 95% CI: -1.41 to -0.56), HOMA-IR (MD = -0.58, 95% CI: -0.77 to -0.38), TG (MD = -11.22 mg dL-1, 95% CI: -19.21 to -3.22), TC (MD = -6.45 mg dL-1, 95% CI: -9.95 to -2.95, LDLc (MD = -8.28 mg dL-1, 95% CI: -11.08 to -5.47), and ALT (MD = -19.71 IU L-1, 95% CI: -36.45 to -2.96). However, no significant effect of L-carnitine supplementation was observed in HDLc (MD = -0.77 mg dL-1, 95% CI: -0.10 to -1.63) or AST (MD = -11.05 IU L-1, 95% CI: -23.08 to 0.99). The duration of carnitine supplementation was negatively associated with mean differences in FBG, as assessed by meta-regression. Conclusion: The current meta-analysis revealed that L-carnitine may have favorable effects on glucolipid profile, especially insulin, FBG, HOMA-IR, TG, TC, LDLc, and ALT levels.