Arsenate reductase of Rufibacter tibetensis is a metallophosphoesterase evolved to catalyze redox reactions.

An arsenate reductase (Car1) from the Bacteroidetes species Rufibacter tibetensis 1351T was isolated from the Tibetan Plateau. The strain exhibits resistance to arsenite [As(III)] and arsenate [As(V)] and reduces As(V) to As(III). Here we shed light on the mechanism of enzymatic reduction by Car1. AlphaFold2 structure prediction, active site energy minimization, and steady-state kinetics of wild-type and mutant enzymes give insight into the catalytic mechanism. Car1 is structurally related to calcineurin-like metallophosphoesterases (MPPs). It functions as a binuclear metal hydrolase with limited phosphatase activity, particularly relying on the divalent metal Ni2+. As an As(V) reductase, it displays metal promiscuity and is coupled to the thioredoxin redox cycle, requiring the participation of two cysteine residues, Cys74 and Cys76. These findings suggest that Car1 evolved from a common ancestor of extant phosphatases by incorporating a redox function into an existing MPP catalytic site. Its proposed mechanism of arsenate reduction involves Cys74 initiating a nucleophilic attack on arsenate, leading to the formation of a covalent intermediate. Next, a nucleophilic attack of Cys76 leads to the release of As(III) and the formation of a surface-exposed Cys74-Cys76 disulfide, ready for reduction by thioredoxin.

Differential responses in the mirror neuron system during imitation of individual emotional facial expressions and association with autistic traits.

The mirror neuron system (MNS), including the inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and superior temporal sulcus (STS) plays an important role in action representation and imitation and may be dysfunctional in autism spectrum disorder (ASD). However, it's not clear how these three regions respond and interact during the imitation of different basic facial expressions and whether the pattern of responses is influenced by autistic traits. Thus, we conducted a natural facial expression (happiness, angry, sadness and fear) imitation task in 100 healthy male subjects where expression intensity was measured using facial emotion recognition software (FaceReader) and MNS responses were recorded using functional near-infrared spectroscopy (fNIRS). Autistic traits were measured using the Autism Spectrum Quotient questionnaire. Results showed that imitation of happy expressions produced the highest expression intensity but a small deactivation in MNS responses, suggesting a lower processing requirement compared to other expressions. A cosine similarity analysis indicated a distinct pattern of MNS responses during imitation of each facial expression with functional intra-hemispheric connectivity between the left IPL and left STS being significantly higher during happy compared to other expressions, while inter-hemispheric connectivity between the left and right IPL differed between imitation of fearful and sad expressions. Furthermore, functional connectivity changes during imitation of each different expression could reliably predict autistic trait scores. Overall, the results provide evidence for distinct patterns of functional connectivity changes between MNS regions during imitation of different emotions which are also associated with autistic traits.

Widespread Distribution of the arsO Gene Confers Bacterial Resistance to Environmental Antimony.

Microbial oxidation of environmental antimonite (Sb(III)) to antimonate (Sb(V)) is an antimony (Sb) detoxification mechanism. Ensifer adhaerens ST2, a bacterial isolate from a Sb-contaminated paddy soil, oxidizes Sb(III) to Sb(V) under oxic conditions by an unknown mechanism. Genomic analysis of ST2 reveals a gene of unknown function in an arsenic resistance (ars) operon that we term arsO. The transcription level of arsO was significantly upregulated by the addition of Sb(III). ArsO is predicted to be a flavoprotein monooxygenase but shows low sequence similarity to other flavoprotein monooxygenases. Expression of arsO in the arsenic-hypersensitive Escherichia coli strain AW3110Δars conferred increased resistance to Sb(III) but not arsenite (As(III)) or methylarsenite (MAs(III)). Purified ArsO catalyzes Sb(III) oxidation to Sb(V) with NADPH or NADH as the electron donor but does not oxidize As(III) or MAs(III). The purified enzyme contains flavin adenine dinucleotide (FAD) at a ratio of 0.62 mol of FAD/mol protein, and enzymatic activity was increased by addition of FAD. Bioinformatic analyses show that arsO genes are widely distributed in metagenomes from different environments and are particularly abundant in environments affected by human activities. This study demonstrates that ArsO is an environmental Sb(III) oxidase that plays a significant role in the detoxification of Sb(III).

Depression mediates the association between insula-frontal functional connectivity and social interaction anxiety.

High rates of comorbidity between depression and anxiety are frequently observed. However, few studies have investigated the relationship between depression and social interaction anxiety using a dimensional approach. The current study aimed to explore the associations between depression and social interaction anxiety with a multivariate approach in a comparably large dataset (n = 194, 95 males). All participants completed a structural and a resting-state functional magnetic resonance imaging (fMRI) scan and self-report measures of depression via Beck's Depression Inventory II and social interaction anxiety by social interaction anxiety scale. Voxel-based morphometry (VBM) results first identified grey matter volumes of insula were positively correlated with depression dimension scores. Next, whole brain seed-to-voxel analyses were conducted using a VBM-identified insula as a seed region to examine associations between depression/social anxiety and functional connectivity. The results suggested that a significant positive effect of depression/social anxiety was found on the connectivity between insula and dorsal lateral prefrontal cortex (dlPFC). Moreover, variations in depression meditated the association between insula-dlPFC connectivity and social interaction anxiety. Overall, the results indicate that individual differences in depression relate more to insula-dlPFC coupling compared to social interaction anxiety.

Experimental and modeling studies of competitive Pb (II) and Cd (II) bioaccumulation by Aspergillus niger.

Co-existence of toxic metals causes complex toxicity to microorganisms during bioremediation in water and soil. This study investigated the immobilization of Pb2+ and Cd2+ by fungus Aspergillus niger, which has been widely applied to environmental remediation. Five treatments were set, i.e., CK (no toxic metals), Pb2+ only, Cd2+ only, Pb2+/Cd2+ = 1:1(molar ratio), and Pb2+/Cd2+ = 2:1. Cadmium induced strong toxicity to the fungus, and maintained the high toxicity during incubation. However, as Pb/Cd ratio increased from 0 to 2, the removal rates of Cd2+ by A. niger were raised from 30 to 50%. The elevated activities of pyruvate dehydrogenase (PDH) and citrate synthetase (CS) enzymes confirmed that Pb addition could stimulate the growth of A. niger. For instance, citric acid concentrations and CS activities were 463.22 mg/L and 78.37 nmol/min/g, respectively, during 3-day incubation as Pb/Cd = 1. However, these two values were as low as ~ 50 with addition of only Cd. It was hence assumed that appropriate co-existence of Pb2+ enhanced microbial activity by promoting TCA cycle of the fungus. Moreover, the SEM analysis and geochemical modeling demonstrated that Pb2+ cations were more easily adsorbed and mineralized on A. niger with respect to Cd2+. Therefore, instead of intensifying metal toxicity, the addition of appropriate Pb actually weakened Cd toxicity to the fungus. This study sheds a bright future on application of A. niger to the remediation of polluted water with co-existence of Pb and Cd. KEY POINTS: • Cd2+ significantly inhibited P consumption, suggesting its high toxicity to A. niger. • Pb2+ stimulated the growth of A. niger by promoting TCA cycle in the cells. • Cd2+ removal by A. niger were improved with co-existence of Pb2+.

An experimental study on the use of a sequencing-batch membrane bioreactor (SBMBR) for the treatment of mixed municipal wastewater.

Several water treatment techniques have been combined using the sequencing batch reactor with the membrane bioreactor for addressing water pollution. However, cleaning of the membrane is dependent on the approach involved as well as the operating conditions. In the present study, the sequencing-batch membrane bioreactor was used to treat real mixed municipal wastewater. The pollutant removal and membrane filtration performances were examined. The results show that the average removal rates of chemical oxygen demand (COD), total nitrogen, NH3-N, total phosphorus, and turbidity were 90.75, 63.52, 92.85, 87.58, and 99.48%, respectively, when the system was in continuous operation for 95 days. The membrane had a significant effect on COD and turbidity removal and provided stable performances for nitrogen and phosphorus removal. By observing the appearance of the membrane modules before and after the cleaning operation, it was concluded that the deposited sludge and granular sediment on the membrane surface can be effectively removed by hydraulic cleaning. In addition, recovery of membrane filtration performance to 60% of that of a new membrane can be achieved. Furthermore, we found that different sequences and duration of cleaning have different effects on the recovery of membrane filtration performance.

Cloning and transcription analysis of the nitrate reductase gene from Haematococcus pluvialis.

OBJECTIVES: To optimize the cultivation media for the growth rate of Haematococcus pluvialis and to study the transcription regulation of the algal nitrate reductase (NR), a key enzyme for nitrogen metabolism. RESULTS: The NR gene from H. pluvialis hd7 consists of 5636 nucleotides, including 14 introns. The cDNA ORF is 2718 bp, encoding a 905 aa protein with three conserved domains. The NR amino acids of H. pluvialis hd7 are hydrophilic and have similarity of 72% compared to that of Dunaliella. NR transcription increased with an increase of nitrate concentration from 0.4 to 1 g/l. A deficiency of nitrogen increased NR transcription significantly. The transcription level of NR increased at phosphorus concentrations from 0.08 to 0.2 g/l, with a maximum at 0.08 g/l. The optimum parameters of medium component for transcription of NR and growth of H. pluvialis were 0.3 g NaNO3/l, 0.045 g KH2PO4/l and 1.08 g sodium acetate/l. CONCLUSIONS: This study provides a better understanding of nitrate regulation in H. pluvialis.

Successful complementary therapy with traditional Chinese medicine in a patient with Qi and Jin deficiency symptoms from adult-onset Still's disease: A case report.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare yet well-documented polygenic and systemic autoinflammatory disease characterized by recurrent spiking fever, transient skin rash, arthralgia, and sore throat. Traditional Chinese medicine (TCM) holds a significant role in complementary and alternative medicine. This study presents a unique case of a female AOSD patient with concurrent Qi and fluid deficiency syndrome who received combined treatment with formulated Zhu Ye Shi Gao Decoction (ZYSGD). CASE PRESENTATION: In this case, a 28-year-old female patient presented with a 15-day history of fever and skin rash accompanied by sore throat, fatigue, myalgia, and arthralgia. Additionally, leucocytosis, aminotransferase abnormalities, and elevated inflammatory factor levels were observed. Infectious diseases, solid tumors, and hematological disorders were all ruled out. Anti-infective treatments proved ineffective, leading to the final diagnosis of AOSD. Glucocorticoid therapy provided only partial relief. Consequently, formulated ZYSGD and hepatoprotective drugs were added to the glucocorticoid treatment. Subsequently, the patient's symptoms and inflammatory biomarkers showed improvement. After discharge, the patient's condition remained stable while continuing the formulated ZYSGD in combination with 4 mg of Medrolol (qd) during a 10-month follow-up period. CONCLUSION: This case report suggests that formulated ZYSGD could be a viable option for complementary and alternative therapy for late-stage AOSD, especially in cases involving both Qi and body fluid imbalances.

Prospects for the Application of Transplantation With Human Amniotic Membrane Epithelial Stem Cells in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multi-organ and systemic autoimmune disease characterized by an imbalance of humoral and cellular immunity. The efficacy and side effects of traditional glucocorticoid and immunosuppressant therapy remain controversial. Recent studies have revealed abnormalities in mesenchymal stem cells (MSCs) in SLE, leading to the application of bone marrow-derived MSCs (BM-MSCs) transplantation technique for SLE treatment. However, autologous transplantation using BM-MSCs from SLE patients has shown suboptimal efficacy due to their dysfunction, while allogeneic mesenchymal stem cell transplantation (MSCT) still faces challenges, such as donor degeneration, genetic instability, and immune rejection. Therefore, exploring new sources of stem cells is crucial for overcoming these limitations in clinical applications. Human amniotic epithelial stem cells (hAESCs), derived from the eighth-day blastocyst, possess strong characteristics including good differentiation potential, immune tolerance with low antigen-presenting ability, and unique immune properties. Hence, hAESCs hold great promise for the treatment of not only SLE but also other autoimmune diseases.

Oral Oxytocin Blurs Sex Differences in Amygdala Responses to Emotional Scenes.

BACKGROUND: Sex differences are shaped both by innate biological differences and the social environment and are frequently observed in human emotional neural responses. Oral administration of oxytocin (OXT), as an alternative and noninvasive intake method, has been shown to produce sex-dependent effects on emotional face processing. However, it is unclear whether oral OXT produces similar sex-dependent effects on processing continuous emotional scenes. METHODS: The current randomized, double-blind, placebo-controlled neuropsychopharmacological functional magnetic resonance imaging experiment was conducted in 147 healthy participants (OXT = 74, men/women = 37/37; placebo = 73, men/women = 36/37) to examine the oral OXT effect on plasma OXT concentrations and neural response to emotional scenes in both sexes. RESULTS: At the neuroendocrine level, women showed lower endogenous OXT concentrations than men, but oral OXT increased OXT concentrations equally in both sexes. Regarding neural activity, emotional scenes evoked opposite valence-independent effects on right amygdala activation (women > men) and its functional connectivity with the insula (men > women) in men and women in the placebo group. This sex difference was either attenuated (amygdala response) or even completely eliminated (amygdala-insula functional connectivity) in the OXT group. Multivariate pattern analysis confirmed these findings by developing an accurate sex-predictive neural pattern that included the amygdala and the insula under the placebo but not the OXT condition. CONCLUSIONS: The results of the current study suggest a pronounced sex difference in neural responses to emotional scenes that was eliminated by oral OXT, with OXT having opposite modulatory effects in men and women. This may reflect oral OXT enhancing emotional regulation to continuous emotional stimuli in both sexes by facilitating appropriate changes in sex-specific amygdala-insula circuitry.

[Treatment of severe active systemic lupus erythematosus by PMC therapy combined langchuang fuzheng jiedu capsule: a clinical observation].

OBJECTIVE: To evaluate the efficacy and safety of PMC therapy (Prednisone, Methotrexate, Chloroquine) combined Langchuang Fuzheng Jiedu Capsule (LFJC), thus choosing a better therapy of integrative medicine for SLE in the period of glucocorticoid use. METHODS: Sixty active SLE patients were randomly assigned to two groups, the control group and the treatment group. Those in the control group received PMC therapy (As for Prednisone, it was given at the daily dose of 1 mg/kg till 2 weeks after the condition being stable or after 8 weeks of treatment. Then the dose was reduced by 10% every two weeks. When the dose was reduced to 0.5 mg/kg daily, it was reduced by 2.5 mg per two weeks. When the dose was reduced to 15 mg daily, the dose was reduced to 2.5 mg per four weeks. As for Methotrexate, 10 mg each time, once a week. As for Chloroquine, 100 mg each time, twice daily), while those in the treatment group received PMC therapy (the same way as that for the control group) combined with LFJC (consisting of Astragalus membranaceus 50 g, Angelica sinensis 20 g, Ligusticum Chuanxiong 20 g, prepared Rehmannia Rhizome 30 g, Herba Serissae 30 g, Centella 30 g, centipede 4 g, scorpions 10 g, nidus versace 12 g, et al., 0.5 g per pill, containing 5.7 g crude drug. When the hormone was given at a large dose, LFJC was administered at 12 pills each time, three times daily). When the hormone was given at a middle dose, LFJC was administered at 8 pills each time, three times daily. When the hormone was given at a small dose, LFJC was administered at 6 pills each time, three times daily. The treatment course was six months. The improvement of symptoms and signs between before and after treatment, SLE disease activity index (SLEDAI), efficacy of Chinese medical syndrome, UPro quantitation, erythrocyte sedimentation rate (ESR), complement 3 (C3), C-reactive protein (CRP), the reduction and withdrawal of hormones, and infection of the respiratory tract were observed. RESULTS: The difference in post-SLEDAI was obviously larger in the treatment group than in the control group (P < 0.05). The fatigue severity scale (FSS) was less after treatment than before treatment in the treatment group, showing statistical difference when compared with that of the control group (P < 0.05). The total effective rate was 93.33% in the treatment group, showing statistical difference when compared with that of the control group (86.66%; chi2 = 6.736, P < 0.05). The ESR decreased after treatment in the treatment group, showing statistical difference when compared with that of the control group (P < 0.01). C3 increased after treatment in the treatment group, showing statistical difference when compared with that of the control group (P < 0.05). The hormone was reduced to (13.70 +/- 5.42) mg/d by the end of the therapeutic course in the treatment group, obviously less than that of the control group [(17.63 +/- 7.80) mg/d, P < 0.05). Seven patients suffered from secondary infection of the respiratory tract infection in the treatment group (5 from upper respiratory tract infection and 2 from lower respiratory tract infection), obviously less than those of the control group (25 from upper respiratory tract infection and 10 from lower respiratory tract infection) (P < 0.05). CONCLUSIONS: PMC combined LFJC was a better treatment program for severe active SLE (SLEDAI > or = 15). It was more safe and effective when compared with using Western medicine alone. It could enhance the efficacy of hormones and help reduction/withdrawal of hormones.

Public exposure to broadband electromagnetic fields and its association with population density and building density: The case study of Beijing.

The gradual increase in electromagnetic field (EMF) exposure levels poses a potential threat to human health and the normal operation of electronic systems. In order to know the environmental EMF conditions, measurements were carried out on roads of about 400 km in the urban area of Beijing, China. The measurement results show that the electric field strength of about 89% of the sampling points is within 3 V/m, and the electric field strength of other sampling points is relatively high. Combined with further spectrum analysis, it was found that the electric field strength of one road section exceeded the national standard limits. In addition, to help quickly identify the general condition of the environmental EMF, a set of procedures for mining the association rules between the electric field strength and population density and building density is proposed in this paper. The final association rules show that the electric field strength is usually lower than 1.5 V/m in areas with medium or lower population density and areas with low building density; the electric field strength in areas with extremely high population density and areas with high building density is usually 1.5-4 V/m; while the electric field strength higher than 4 V/m mainly occurs in areas with extremely high population density. It is recommended to focus on strengthening the monitoring of EMF in areas with extremely high population density, and at the same time continuously pay attention to the trend of the urban EMF levels, so as to achieve early warning and treatment of relevant risks.

Ecological drivers and potential functions of viral communities in flooded arsenic-contaminated paddy soils.

This work revealed the profile of viral communities in paddy soils with different levels of arsenic (As) contamination during the flooded period. The structure of viral communities differed significantly in highly and moderately As-contaminated soils. The diversity of soil viral communities under high As contamination decreased. Siphoviridae, Podoviridae, Myoviridae, and Microviridae were the dominant viral families in all samples, and the relative abundances of five of the top 20 viral genera were significantly different between highly and moderately As-contaminated groups. Seventeen dissimilatory As(V)-reducing bacteria were predicted to host 161 viral operational taxonomic units (vOTUs), mainly affiliated with the genera of Sulfurospirillum, Deferribacter, Bacillus and Fusibacter. Among them, 28 vOTUs were also associated with Fe(III)-reducing bacteria, which belonged to different species of the genus Shewanella. Procrustes analysis showed that the community structure of soil viruses was strongly correlated with both prokaryotic community structure and geochemical properties. Random forest analyses revealed that the Total-Fe, DCB-Fe and oxalate-Fe were the most significant variables on viral community richness, while the total-As concentration was an important factor on the Shannon index. Furthermore, As resistance genes (ArsC, ArsR and ArsD), As methylation genes (arsM) and As transporter genes (Pst and Pit) were identified among the auxiliary metabolic genes (AMGs) of the virome. This work revealed that the viruses might influence microbial adaptation in response to As-induced stress, and provided a perspective on the potential virus-mediated biogeochemical cycling of As.

Regional superficial amygdala resting-state functional connectivity in adults infers childhood maltreatment severity.

Background: Childhood maltreatment (CM) is a potential risk factor for some neuropsychiatric disorders in adulthood (e.g. depression and anxiety) and alters trajectories of brain development. Accumulating evidence suggests that functional connectivity of the limbic system, especially the amygdala, is highly associated with childhood maltreatment, although not all studies have found this. These inconsistent results may be due to differential alterations of amygdala resting-state functional connectivity (rsFC) following childhood maltreatment. Objective: Our aim was to investigate the relationship between the rsFC of amygdala subregions and CM severity, as well as to develop a stable rsFC-based model for inferring the severity of CM. Methods: In this study, we employed the Childhood Trauma Questionnaire (CTQ) to assess CM severity in each individual. We explored the relationship between the rsFC of amygdala subregions (i.e. centromedial -CMA, basolateral -BLA, superficial-SFA amygdala) and CM experience in a discovery dataset of n = 110 healthy Chinese participants by linear multiple regression analysis. Subsequent dimensional and categorical approach were performed to elucidate the relationship between rsFCs and CM severity and CM subtypes, respectively. A support vector regression model was then conducted to validate the associations between rsFCs and total CTQ scores. Moreover, we also verified the model into another independent replication dataset (n = 38). Results: Our findings suggested that childhood maltreatment was negatively associated with rsFC between the right superficial amygdala and perigenual anterior cingulate cortex (pgACC)/postcentral gyrus (PCG) but not the other two amygdala subregions. Moreover, SFA-pgACC coupling was more associated with physical neglect whereas the SFA-PCG was more related to emotional neglect. In addition, supervised machine learning confirmed that using these two rsFCs as predictors could stably estimate continuous maltreatment severity in both discovery and replication datasets. Conclusion: The current study supports that the rsFCs of superficial amygdala are related to childhood maltreatment and which may be a potential biomarker for the effects of childhood maltreatment-related psychiatric disorders (i.e. depression and anxiety).

Fear of missing out (FOMO) associates with reduced cortical thickness in core regions of the posterior default mode network and higher levels of problematic smartphone and social media use.

BACKGROUND AND AIMS: Fear of missing out (FOMO) promotes the desire or urge to stay continuously connected with a social reference group and updated on their activities, which may result in escalating and potentially addictive smartphone and social media use. The present study aimed to determine whether the neurobiological basis of FOMO encompasses core regions of the reward circuitry or social brain, and associations with levels of problematic smartphone or social media use. METHODS: We capitalized on a dimensional neuroimaging approach to examine cortical thickness and subcortical volume associations in a sample of healthy young individuals (n = 167). Meta-analytic network and behavioral decoding analyses were employed to further characterize the identified regions. RESULTS: Higher levels of FOMO associated with lower cortical thickness in the right precuneus. In contrast, no associations between FOMO and variations in striatal morphology were observed. Meta-analytic decoding revealed that the identified precuneus region exhibited a strong functional interaction with the default mode network (DMN) engaged in social cognitive and self-referential domains. DISCUSSION AND CONCLUSIONS: Together the present findings suggest that individual variations in FOMO are associated with the brain structural architecture of the right precuneus, a core hub within a large-scale functional network resembling the DMN and involved in social and self-referential processes. FOMO may promote escalating social media and smartphone use via social and self-referential processes rather than reward-related processes per se.

Analysis on the interactions between the first introns and other introns in mitochondrial ribosomal protein genes.

It is realized that the first intron plays a key role in regulating gene expression, and the interactions between the first introns and other introns must be related to the regulation of gene expression. In this paper, the sequences of mitochondrial ribosomal protein genes were selected as the samples, based on the Smith-Waterman method, the optimal matched segments between the first intron and the reverse complementary sequences of other introns of each gene were obtained, and the characteristics of the optimal matched segments were analyzed. The results showed that the lengths and the ranges of length distributions of the optimal matched segments are increased along with the evolution of eukaryotes. For the distributions of the optimal matched segments with different GC contents, the peak values are decreased along with the evolution of eukaryotes, but the corresponding GC content of the peak values are increased along with the evolution of eukaryotes, it means most introns of higher organisms interact with each other though weak bonds binding. By comparing the lengths and matching rates of optimal matched segments with those of siRNA and miRNA, it is found that some optimal matched segments may be related to non-coding RNA with special biological functions, just like siRNA and miRNA, they may play an important role in the process of gene expression and regulation. For the relative position of the optimal matched segments, the peaks of relative position distributions of optimal matched segments are increased during the evolution of eukaryotes, and the positions of the first two peaks exhibit significant conservatism.

Eltrombopag improves refractory thrombocytopenia in patients with Sjögren's syndrome.

INTRODUCTION: Eltrombopag, a kind of thrombopoietin (TPO) receptor agonist, plays the role on the megakaryocyte to activate the platelet production and rapidly increase the number of circulating platelets in patients with primary immune thrombocytopenia (ITP). Eltrombopag provides an opportunity for rapid tapering and/or cessation of corticosteroid therapy. However, it is not clear about the platelet response to Eltrombopag in ITP associated with Sjögren's Syndrome(SS). METHODS: A retrospective research was conducted on the clinical course of three patients, each with ITP secondary to SS, and initially received therapy of corticosteroids or other immunomodulatory. They took this drug for bleeding diseases. Referring to the description, Eltrombopag was prescribed and adjusted with an initial dose of 25 mg daily, then weekly, then monthly according to the monitoring of platelet counts. RESULTS: All patients maintained a satisfactory level of platelet counts (>100,000/mm3 for >2 years) following corticosteroid withdrawal. Meanwhile, Eltrombopag was well-tolerated, and there were no adverse effects, such as thrombotic events. CONCLUSIONS: Eltrombopag is effective and safe for patients with ITP associated with SS during corticosteroid withdrawal. Thus it may be a crucial therapeutic strategy for reducing corticosteroid-related side effects in SS patients with ITP.

Investigation of the mechanism of action of Shengxuexiaoban Capsules against primary immune thrombocytopenia using network pharmacology and experimental validation.

BACKGROUND: Shengxuexiaoban Capsules (SC) is a classical prescription in traditional Chinese medicine (TCM) and has been clinically adopted in the treatment of primary immune thrombocytopenia (ITP) in China. However, the underlying mechanisms of the actions of SC on ITP remain clear. METHODS: A network pharmacology approach was adopted to investigate the underlying molecular mechanism of SC in treating ITP, and the effects of SC on the proliferation, differentiation, and apoptosis of megakaryocyte (MK) and on the ITP animal model were investigated. RESULTS: Network pharmacology analysis found 128 active compounds and 268 targets of these compounds in SC, as well as 221 ITP-related targets. The topological analysis found a central network containing 82 genes, which were significantly associated with the regulation of transcription, cell proliferation, apoptosis processes, the PI3K-AKT signaling pathway, the MAPK signaling pathway, and the ERK1 and ERK2 cascades. It showed that SC increased the proliferation and differentiation of MK, but had no significant impact on MK apoptosis in vivo. The addition of SC increased the gene expression of several potential targets, including STAT3, KDR, CASP3, and TGFB1. In addition, SC administration elevated the protein expression of p-AKT and inhibit the protein expression of p-ERK, but has no impact on the protein expression of p-P38. Moreover, SC could improve haemogram parameters, coagulation indicators, and the proliferation and differentiation of MK in the ITP animal model. CONCLUSIONS: The present study systematically elucidated the underlying mechanisms of SC against ITP and provided an efficient strategy to discover the pharmacological mechanism of TCM. It may strengthen the understanding of SC and facilitate more application of this formula in the treatment of ITP.

Scorpion venom polypeptide governs alveolar macrophage M1/M2 polarization to alleviate pulmonary fibrosis.

The onset of connective tissue disease-related interstitial lung disease (CTD-ILD) is generally insidious and progressive, with pulmonary fibrosis in the middle stage, and eventually respiratory failure and death. This study aimed to explore the role of scorpion venom polypeptide (SVP), the primary active constituent of the entire scorpion, in alveolar macrophages and pulmonary fibrosis. Pulmonary fibrosis mouse models were established, and then SVP and JAK inhibitor (tofacitinib) was used to treat models. Alveolar macrophages were isolated and the impacts of SVP on M1/M2 polarization and the JAK/STAT6 pathway in vitro were assessed. H&E and Masson staining revealed that SVP and tofacitinib treatment alleviated lung damage and fibrosis. They also hindered the M2-polarization of macrophages in lung tissue and declined cytokine levels associated with M2 polarization (IL-4, IL-13) and fibrosis drivers (TGF-ß, VEGF) in mice. Consistent with the trend presented by tofacitinib treatment, SVP suppressed the phosphorylation of proteins in the JAK/STAT6 pathway. In addition, the in vitro treatment of SVP on the isolated macrophages represented consistent results with in vivo experiments. The findings of the present study indicated that SVP suppressed the JAK/STAT6 signaling pathway, hindered alveolar macrophage M2-type polarization, and possessed the potential to ameliorate pulmonary fibrosis.