Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states.

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Intraspecific alternative phenotypes contribute to variation in species' strategies for growth.

Ecologists have historically sought to identify the mechanisms underlying the maintenance of local species diversity. High-dimensional trait-based relationships, such as alternative phenotypes, have been hypothesized as important for maintaining species diversity such that phenotypically dissimilar individuals compete less for resources but have similar performance in a given environment. The presence of alternative phenotypes has primarily been investigated at the community level, despite the importance of intraspecific variation to diversity maintenance. The aims of this research are to (1) determine the presence or absence of intraspecific alternative phenotypes in three species of tropical tree seedlings, (2) investigate if these different species use the same alternative phenotypes for growth success, and (3) evaluate how findings align with species co-occurrence patterns. We model species-specific relative growth rate with individual-level measurements of leaf mass per area (LMA) and root mass fraction (RMF), environmental data, and their interactions. We find that two of the three species have intraspecific alternative phenotypes, with individuals within species having different functional forms leading to similar growth. Interestingly, individuals within these species use the same trait combinations, high LMA × low RMF and low LMA × high RMF, in high soil nutrient environments to acquire resources for higher growth. This similarity among species in intraspecific alternative phenotypes and variables that contribute most to growth may lead to their negative spatial co-occurrence. Overall, we find that multiple traits or interactions between traits and the environment drive species-specific strategies for growth, but that individuals within species leverage this multi-dimensionality in different ways for growth success.

Neural stem cell-derived exosomes regulate cell proliferation, migration, and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia.

BACKGROUND: Our previous study found that mouse embryonic neural stem cell (NSC)-derived exosomes (EXOs) regulated NSC differentiation via the miR-9/Hes1 axis. However, the effects of EXOs on brain microvascular endothelial cell (BMEC) dysfunction via the miR-9/Hes1 axis remain unknown. Therefore, the current study aimed to determine the effects of EXOs on BMEC proliferation, migration, and death via the miR-9/Hes1 axis. METHODS: Immunofluorescence, quantitative real-time polymerase chain reaction, cell counting kit-8 assay, wound healing assay, calcein-acetoxymethyl/propidium iodide staining, and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs. RESULTS: EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. The overexpression of miR-9 promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. Moreover, miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death. Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death. Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice. Meanwhile, EXO treatment improved cerebrovascular alterations. CONCLUSION: NSC-derived EXOs can promote BMEC proliferation and migration and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions. Therefore, EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.

H2S inhibits LiCl/pilocarpine-induced seizures and promotes neuroprotection by regulating TRPV2 expression via the AC3/cAMP/PKA pathway.

It is widely acknowledged that epilepsy is a neurological disorder characterized by recurrent and atypical neuronal discharges, resulting in transient dysfunction within the brain. The protective role of hydrogen sulfide (H2S) in epilepsy has been elucidated by recent studies, but the underlying mechanisms remain poorly understood. To investigate this, the concentration of H2S was measured by spectrophotometry and a fluorescent probe in LiCl/Pilocarpine (LiCl/Pilo)-induced seizures in rats. The localization of proteins was examined using immunofluorescence. Electroencephalogram and behavioral tests were employed to evaluate the occurrence of seizures. Neuropathological changes in the hippocampus were examined by hematoxylin-eosin staining, Nissl staining, and transmission electron microscopy. Through proteomics and bioinformatics analysis, we identified the differential proteins in the hippocampus of rats following H2S intervention. Protein changes were detected through western blotting. The results showed that H2S treatment significantly alleviated seizures and minimized post-seizures neurological damage in rats. Proteomics analysis revealed adenylate cyclase 3 (AC3) as a protein potentially targeted by H2S. Moreover, the AC3 activator forskolin reversed the downregulation effect of H2S on the AC3/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/transient receptor potential vanilloid 2 (TRPV2) signaling pathway. In conclusion, H2S targets and downregulates the expression of AC3, thereby modulating the AC3/cAMP/PKA signaling pathway to regulate the expression of TRPV2 in LiCl/Pilo-induced seizures, ultimately leading to seizure inhibition and neuroprotection.

Reusable Solid-form Phase-Selective Organogelators for Rapid and Efficient Remediation of Crude Oil Spill.

Phase-selective organogelators (PSOGs) are considered as a prospective tool for their application in oil spill remediation. However, the number of reports on the PSOGs that can be used in powder form for prompt phase-selective gelation of crude oils is still limited. In this study, a series of compounds with l-mandelic acid as the scaffold bearing different amino acid fragments have been prepared. Also, the gelation behaviors and properties of these derivatives toward organic liquids, product oils, and a type of Chinese crude oil were investigated via heating-and-cooling process, stirring, or resting operation. Besides, the micromorphologies of the resulting gels and the driving forces for the gel formation have been studied by scanning electron microscopy, Fourier transform infrared, UV spectroscopy, concentration-dependent 1H NMR, and X-ray diffraction. Particularly, gelator C15-Phe-Mac-Nap was shown to have the capability of congealing the Chinese crude oil selectively from water in powder form with a relatively lower gelator dosage, as compared with the other gelators we reported in the current and previous works. Moreover, gelator C15-Phe-Mac-Nap displayed some advantageous behaviors such as the reusability of gelator, excellent mechanical and chemical stability of the crude oil gels, and nontoxicity of the gelator in the aquatic environment, indicating its great potential application value for marine oil spill remediation.

Photocontrolled chiroptical switch based on the self-assembly of azobenzene-bridged bis-tryptophan enantiomers.

Chirality dynamic tuning plays fundamental roles in chemistry, material science and biological system. Herein, a pair of azobenzene-bridged bis-tryptophan enantiomers (Azo-di-d/l-Trp) were designed and synthesized via simple reactions. With the fuel of glucono-δ-lactone (GdL), releasing protons during its hydrolysis, the alkaline solution of Azo-di-d/l-Trp gradually self-assembled into contrast chiral helical structures and displayed magnitude and mirror image of circular dichroism (CD) signals. While the chiral helices converted to CD silent nanoparticles when the azobenzene moiety isomerized from trans- to cis-form under UV irradiation. More importantly, this chiroptical switch, displaying reversible interconversion between chiral amplification and silent, can be smartly controlled via photoirradiation at various wavelengths.

Statistical Information Affects Spoken Word Recognition of Tone Languages in Stutterers: Evidence From an Auditory-Perceptual Gating Study.

PURPOSE: Previous studies have shown that individuals who stutter exhibit abnormal speech perception in addition to disfluent production as compared with their nonstuttering peers. This study investigated whether adult Chinese-speaking stutterers are still able to use knowledge of statistical regularities embedded in their native language to recognize spoken words and, if so, how much acoustic information is needed to trigger this information. METHOD: Seventeen stutterers and 20 typical, nonstuttering controls participated in a gating experiment. All participants listened to monosyllabic words that consisted of syllables and lexical tones and were segmented into eight successive gates. These words differed in syllable token frequency and syllable-tone co-occurrence probability in line with a Chinese spoken word corpus. The correct syllable-only, correct tone-only, correct syllable-tone word, and correct syllable-incorrect tone responses were analyzed between the two groups using mixed-effects models. RESULTS: Stutterers were less accurate overall than controls, with fewer correct syllables, tones, and their combination as words. However, stutterers showed consistent and reliable perceptual patterns triggered by statistical information of speech, as reflected by more accurate responses to high-frequency syllables, high-probability tones, and tone errors all in manners similar to those of nonstuttering controls. CONCLUSIONS: Stutterers' atypical speech perception is not due to a lack of statistical learning. Stutterers were able to perceive spoken words with phonological tones based on statistical regularities embedded in their native speech. This finding echoes previous production studies of stuttering and lends some support for a link between perception and production. Implications of pathological, diagnostic, and therapeutic conditions of stuttering are discussed.

Tone Deafness in Music Does Not Preclude Distributional Learning of Nonnative Tonal Languages in Individuals With Congenital Amusia.

PURPOSE: Previous studies have shown that individuals with congenital amusia exhibit deficient pitch processing across music and language domains. This study investigated whether adult Chinese-speaking listeners with amusia were still able to learn Thai lexical tones based on stimulus frequency of statistical distribution via distributional learning, despite their degraded lexical tone perception. METHOD: Following a pretest-training-posttest design, 21 amusics and 23 typical, musically intact listeners were assigned into bimodal and unimodal distribution conditions. Listeners were asked to discriminate minimal pairs of Thai mid-level tone and falling tone superimposed on variable base syllables and uttered by different speakers. The perceptual accuracy for each test session and improvement from pretest to posttest were collected and analyzed between the two groups using generalized mixed-effects models. RESULTS: When discriminating Thai lexical tones, amusics were less accurate than typical listeners. Nonetheless, similarly to control listeners, perceptual gains from pretest to posttest were observed in bimodally rather than unimodally trained amusics, as evidenced by both trained and nontrained test words. CONCLUSIONS: Amusics are able to learn lexical tones in a second or foreign context of speech. This extends previous research by showing that amusics' distributional learning of linguistic pitch remains largely preserved despite their degraded pitch processing. It is thus likely that manifestations of amusia in speech could not result from their abnormal statistical learning mechanism. This study meanwhile provides a heuristic approach for future studies to apply this paradigm into amusics' treatment to mitigate their pitch-processing disorder.

Distributional learning of musical pitch despite tone deafness in individuals with congenital amusia.

Congenital amusia is an innate and lifelong deficit of music processing. This study investigated whether adult listeners with amusia were still able to learn pitch-related musical chords based on stimulus frequency of statistical distribution, i.e., via distributional learning. Following a pretest-training-posttest design, 18 amusics and 19 typical, musically intact listeners were assigned to bimodal and unimodal conditions that differed in distribution of the stimuli. Participants' task was to discriminate chord minimal pairs, which were transposed to a novel microtonal scale. Accuracy rates for each test session were collected and compared between the two groups using generalized mixed-effects models. Results showed that amusics were less accurate than typical listeners at all comparisons, thus corroborating previous findings. Importantly, amusics-like typical listeners-demonstrated perceptual gains from pretest to posttest in the bimodal condition (but not the unimodal condition). The findings reveal that amusics' distributional learning of music remains largely preserved despite their deficient music processing. Implications of the results for statistical learning and intervention programs to mitigate amusia are discussed.

Encoding category-level and context-specific phonological information at different stages: An EEG study of Mandarin third-tone sandhi word production.

Pronunciation of words or morphemes may vary systematically in different phonological contexts, but it remains unclear how different levels of phonological information are encoded in speech production. In this study, we investigated the online planning process of Mandarin Tone 3 (T3) sandhi, a case of phonological alternation whereby a low-dipping tone (T3) changes to a Tone 2 (T2)-like rising tone when followed by another T3. To examine the time course of the encoding of the abstract category-level (underlying form) and context-specific phonological form (surface form) of T3, we conducted an electroencephalographic (EEG) study with a phonologically-primed picture naming task and examined the event-related potentials (ERPs) time-locked to the stimulus onset as well as speech response onset. The behavioral results showed that targets primed by T3 or T2 primes yielded shorter naming latencies than those primed by control primes. Importantly, the EEG data revealed that T3 primes elicited larger positive amplitude over broad frontocentral regions roughly in the 320-550 ms time window of stimulus-locked ERP and -500 to -400 ms time window of response-locked ERP, whereas T2 primes elicited larger negative amplitude over left frontocentral regions roughly in the -240 to -100 ms time window of response-locked ERP. These results indicate that the underlying and the surface form are encoded at different processing stages. The former presumably occurs in the earlier phonological encoding stage, while the latter probably occurs in the later phonetic encoding or motor preparation stage. The current study offers important implications for understanding the processing of phonological alternations and tonal encoding in Chinese word production.

Dehydrogenative Synthesis of Quinolines and Quinazolines via Ligand-Free Cobalt-Catalyzed Cyclization of 2-Aminoaryl Alcohols with Ketones or Nitriles.

We present a convenient and efficient protocol to synthesize quinolines and quinazolines in one pot under mild conditions. A variety of substituted quinolines were synthesized in good to excellent yields (up to 97% yield) from the dehydrogenative cyclizations of 2-aminoaryl alcohols and ketones catalyzed by readily available Co(OAc)2·4H2O. This cobalt catalytic system also showed high activity in the reactions of 2-aminobenzyl alcohols with nitriles, affording various quinazoline derivatives (up to 95% yield). The present protocol offers an environmentally benign approach for the synthesis of N-heterocycles by employing an earth-abundant cobalt salt under ligand-free conditions.

The effects of alphabetic literacy, linguistic-processing demand and tone type on the dichotic listening of lexical tones.

Brain lateralization of lexical tone processing remains a matter of debate. In this study we used a dichotic listening paradigm to examine the influences of the knowledge of Jyutping (a romanization writing system which provides explicit Cantonese tone markers), linguistic-processing demand and tone type on the ear preference pattern of native tone processing in Hong Kong Cantonese speakers. While participants with little knowledge of Jyutping showed a previously reported left-ear advantage (LEA), those with a good level of Jyutping expertise exhibited either a right-ear advantage or bilateral processing during lexical tone identification and contour tone discrimination, respectively. As for the effect of linguistic-processing demand, while an LEA was found in acoustic/phonetic perception situations, this advantage disappeared and was replaced by a bilateral pattern in conditions that involved a greater extent of linguistic processing, suggesting an increased involvement of the left hemisphere. Regarding the effect of tone type, both groups showed an LEA in level tone discrimination, but only the Jyutping group demonstrated a bilateral pattern in contour tone discrimination. Overall, knowledge of written codes of tones, greater degree of linguistic processing and contour tone processing seem to influence the brain lateralization of lexical tone processing in native listeners of Cantonese by increasing the recruitment of the left-hemisphere language network.

The Effects of Training Variability and Pitch Aptitude on the Overnight Consolidation of Lexical Tones.

PURPOSE: Although variability of training materials has the potential to benefit the learning of lexical tones, the benefit is contingent on an individual's pitch aptitude. Previous studies did not segregate immediate learning and consolidation after an overnight interval, and little is known about how pitch aptitude differences affect consolidation. This study examined whether pitch aptitude predicts overnight consolidation of Cantonese level tones through high-variability (HV) and low-variability (LV) training. METHOD: Two groups of Mandarin-speaking participants were first assessed in terms of pitch threshold and tone discrimination, which tapped into different aspects of pitch aptitude. They then received Cantonese level tone identification training in either an HV or an LV condition. The participants were trained in the evening, were tested after training, and returned after 24 hr for overnight consolidation assessment. RESULTS: The results indicate that pitch aptitude, measured through pitch threshold, may have predicted overnight consolidation and training progress of the HV group but not those of the LV group. In the HV group, compared with high-aptitude learners, low-aptitude learners benefited temporarily from training variability but did not consolidate the tonal knowledge as much as their high-aptitude counterparts did after 24 hr. CONCLUSIONS: The findings suggest that individual learners had difficulty learning nonnative tones by virtue of memory consolidation. Higher pitch aptitude ability (pitch threshold) may provide protection against the decay of learned tones and facilitate tone consolidation. The findings imply that the early emergence of tonal representation is a dynamic process among individuals of nonnative speakers who are exposed to training variability. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20539998.

Modelling representations in speech normalization of prosodic cues.

The lack of invariance problem in speech perception refers to a fundamental problem of how listeners deal with differences of speech sounds produced by various speakers. The current study is the first to test the contributions of mentally stored distributional information in normalization of prosodic cues. This study starts out by modelling distributions of acoustic cues from a speech corpus. We proceeded to conduct three experiments using both naturally produced lexical tones with estimated distributions and manipulated lexical tones with f0 values generated from simulated distributions. State of the art statistical techniques have been used to examine the effects of distribution parameters in normalization and identification curves with respect to each parameter. Based on the significant effects of distribution parameters, we proposed a probabilistic parametric representation (PPR), integrating knowledge from previously established distributions of speakers with their indexical information. PPR is still accessed during speech perception even when contextual information is present. We also discussed the procedure of normalization of speech signals produced by unfamiliar talker with and without contexts and the access of long-term stored representations.

Impaired Categorical Perception of Speech Sounds Under the Backward Masking Condition in Adults Who Stutter.

PURPOSE: Evidence increasingly indicates that people with developmental stuttering have auditory perception deficits. Our previous research has indicated similar but slower performance in categorical perception of the speech sounds under the quiet condition in children who stutter and adults who stutter (AWS) compared with their typically fluent counterparts. We hypothesized that the quiet condition may not be sufficiently sensitive to reveal subtle perceptual deficiencies in people who stutter. This study examined this hypothesis by testing the categorical perception of speech and nonspeech sounds under backward masking condition (i.e., a noise was presented immediately after the target stimuli). METHOD: Fifteen Cantonese-speaking AWS and 15 adults who do not stutter (AWNS) were tested on the categorical perception of four stimulus continua, namely, consonant varying in voice onset time (VOT), vowel, lexical tone, and nonspeech, under the backward masking condition using identification and discrimination tasks. RESULTS: AWS demonstrated a broader boundary width than AWNS in the identification task. AWS also exhibited a worse performance than AWNS in the discrimination of between-category stimuli but a comparable performance in the discrimination of within-category stimuli, indicating reduced sensitivity to sounds that belonged to different phonemic categories among AWS. Moreover, AWS showed similar patterns of impaired categorical perception across the four stimulus types, although the boundary location on the VOT continuum occurred at an earlier point in AWS than in AWNS. CONCLUSIONS: The findings provide robust evidence that AWS exhibit impaired categorical perception of speech and nonspeech sounds under the backward masking condition. Temporal processing (i.e., VOT manipulation), frequency/spectral/formant processing (i.e., lexical tone or vowel manipulations), and nonlinguistic pitch processing were all found to be impaired in AWS. Altogether, the findings support the hypothesis that AWS might be less efficient in accessing the phonemic representations when exposed to a demanding listening condition. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20249718.

Effects of fire disturbance on species and functional compositions vary with tree sizes in a tropical dry forest.

Background: Disturbances are crucial in determining forest biodiversity, dynamics, and ecosystem functions. Surface fire is a significant disturbance in tropical forests, but research on the effect of surface fire on structuring species and functional composition in a community through time remains scarce. Using a 20-year dataset of tree demography in a seasonal evergreen tropical forest in Thailand, we specifically addressed two essential questions: (1) What is the pattern of temporal turnover in species and functional composition in a community with frequent fire disturbance? (2) How did the temporal turnover vary with tree size? Methods: We analyzed species compositional and functional temporal turnovers in four different tree size classes among five tree censuses. We quantified species turnover by calculating Bray-Curtis dissimilarity, and investigated its underlying mechanisms by comparing pairwise dissimilarity of functional traits with simulations from null models. If fire disturbances contribute more to a stochastic process, the functional composition would display a random pattern. However, if they contribute more towards a deterministic process, the functional composition should reveal a non-random pattern. Results: Over 20 years (1994-2014), we observed changes in species composition, whereas functional composition remained relatively stable. The temporal turnover patterns of species and functional compositions varied with tree sizes. In particular, temporal functional turnover shifted very little for large trees, suggesting that changes in species composition of larger trees are contributed by species with similar functional traits through time. The temporal functional composition turnovers of smaller trees (DBH ≤ 5 cm) were mostly at random. We detected a higher functional turnover than expected by null models in some quadrats throughout the 50-ha study plot, and their observed turnover varied with diameter classes. Conclusions: Species compositional changes were caused by changes in the abundance of species with similar functional traits through time. Temporal functional turnover in small trees was random in most quadrats, suggesting that the recruits came from the equal proportions of surviving trees and new individuals of fast-growing species, which increased rapidly after fires. On the other hand, functional composition in big trees was more likely determined by surviving trees which maintained higher functional similarities than small trees through time. Fire disturbance is important for ecosystem functions, as changing forest fire frequency may alter forest turnover, particularly in functional composition in the new recruits of this forest.

The Perception of Lexical Tone and Intonation in Whispered Speech by Mandarin-Speaking Congenital Amusics.

PURPOSE: A fundamental feature of human speech is variation, including the manner of phonation, as exemplified in the case of whispered speech. In this study, we employed whispered speech to examine an unresolved issue about congenital amusia, a neurodevelopmental disorder of musical pitch processing, which also affects speech pitch processing such as lexical tone and intonation perception. The controversy concerns whether amusia is a pitch-processing disorder or can affect speech processing beyond pitch. METHOD: We examined lexical tone and intonation recognition in 19 Mandarin-speaking amusics and 19 matched controls in phonated and whispered speech, where fundamental frequency (f o) information is either present or absent. RESULTS: The results revealed that the performance of congenital amusics was inferior to that of controls in lexical tone identification in both phonated and whispered speech. These impairments were also detected in identifying intonation (statements/questions) in phonated and whispered modes. Across the experiments, regression models revealed that f o and non-f o (duration, intensity, and formant frequency) acoustic cues predicted tone and intonation recognition in phonated speech, whereas non-f o cues predicted tone and intonation recognition in whispered speech. There were significant differences between amusics and controls in the use of both f o and non-f o cues. CONCLUSION: The results provided the first evidence that the impairments of amusics in lexical tone and intonation identification prevail into whispered speech and support the hypothesis that the deficits of amusia extend beyond pitch processing. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19302275.

YB-1 Recruits Drosha to Promote Splicing of pri-miR-192 to Mediate the Proangiogenic Effects of H2S.

Aims: The genes targeted by miRNAs have been well studied. However, little is known about the feedback mechanisms to control the biosynthesis of miRNAs that are essential for the miRNA feedback networks in the cells. In this present study, we aimed at examining how hydrogen sulfide (H2S) promotes angiogenesis by regulating miR-192 biosynthesis. Results: H2S promoted in vitro angiogenesis and angiogenesis in Matrigel plugs embedded in mice by upregulating miR-192. Knockdown of the H2S-generating enzyme cystathionine γ-lyase (CSE) suppressed in vitro angiogenesis, and this suppression was rescued by exogenous H2S donor NaHS. Plakophilin 4 (PKP4) served as a target gene of miR-192. H2S up-regulated miR-192 via the VEGFR2/Akt pathway to promote the splicing of primary miR-192 (pri-miR-192), and it resulted in an increase in both the precursor- and mature forms of miR-192. H2S translocated YB-1 into the nuclei to recruit Drosha to bind with pri-miR-192 and promoted its splicing. NaHS treatment promoted angiogenesis in the hindlimb ischemia mouse model and the skin-wound-healing model in diabetic mice, with upregulated miR-192 and downregulated PKP4 on NaHS treatment. In human atherosclerotic plaques, miR-192 levels were positively correlated with the plasma H2S concentrations. Innovation and Conclusion: Our data reveal a role of YB-1 in recruiting Drosha to splice pri-miR-192 to mediate the proangiogenic effect of H2S. CSE/H2S/YB-1/Drosha/miR-192 is a potential therapeutic target pathway for treating diseases, including organ ischemia and diabetic complications. Antioxid. Redox Signal. 36, 760-783. The Clinical Trial Registration number is 2016-224.

Trans-anethole attenuates diet-induced nonalcoholic steatohepatitis through suppressing TGF-ß-mediated fibrosis.

BACKGROUND: Nonalcoholic Steatohepatitis (NASH) is the most severe type of non-alcoholic fatty liver disease (NAFLD) and one of the most common chronic liver diseases, leading to the increased risk of liver failure, cirrhosis and hepatocellular carcinoma. Trans-anethole was reported to have anti-inflammatory, anti-obesity and anti-diabetic activities. However, its role in NASH remains unknown. Therefore, we aimed to explore the effect of Trans-anethole on NASH. METHODS: Eight-week-old C57BL/6 mice were fed on a methionine- and choline-deficient (MCD) diet for 8 weeks to induce NASH in mice, and on the meanwhile, mice were also orally administrated with or without 100 mg/kg Trans-anethole daily to evaluate the effect of Trans-anethole on NASH. RESULTS: Trans-anethole dose-dependently ameliorated liver injury in MCD diet-fed mice, then the most effective dose of Trans-anethole 100 mg/kg was chosen. Trans-anethole significantly attenuated hepatic steatosis, inflammation and hepatic fibrosis in MCD diet-induced NASH mice. Moreover, Trans-anethole reduced hepatic fibrosis by inhibiting transforming growth factor-beta signaling pathway both in vivo and in vitro. CONCLUSION: Trans-anethole effectively ameliorated NASH in MCD diet-fed mice, which suggested that Trans-anethole might serve as a therapeutic strategy for NASH.