Five-Year Results of Spontaneous Isolated Superior Mesenteric Artery Dissection from Two Teaching Hospitals in China.

BACKGROUND: To present 5-year results of management on spontaneous isolated superior mesenteric artery dissection (SISMAD) from 2 teaching hospitals in China. METHODS: The clinical data of 41 patients with SISMAD were retrospectively collected from 2 teaching hospitals between December 2016 and December 2021. Therapeutic methods mainly included open surgery, endovascular management, and conservative therapy. Patients' demographics, total number of WBC (White blood cell, WBC), the percentage of NEUT (Neutrophil), the level of CRP (C-reactive protein, CRP), duration of abdominal pain on admission, YOO classification of SISMAD, angle of superior mesenteric artery to abdominal aorta (ASA), length of hospital stays, and vascular remodeling rate of SMA between endovascular and conservative groups were analyzed. RESULTS: A total of 41 patients with SISMAD were finally included in this study. Their average age was 53.4 ± 7.1 years old, ranging from 35 to 68 years old. Among these patients, 1 patient suffered emergent open surgery because of the intestinal necrosis. The other 40 patients were treated conservatively at first, but 13 of them were transitioned into endovascular management due to persistent abdominal pain. Regarding the imaging analysis, IIS and IVS types of YOO classification were more in the endovascular group (13 patients) than the conservative group (27 patients). The length of hospital stays (P = 0.003) and the vascular remodeling rate of SMA were significantly different between 2 groups (P = 0.002), while the time of abdominal pain on admission, the infection markers (WBC, CRP, NEUT) and ASA were not significantly different between the 2 groups. CONCLUSIONS: In SISMAD, patients without any signs of peritonitis and intestinal necrosis may be treated conservatively firstly, and then transitioned into endovascular management if abdominal pain is not improved within 48 hr. IIS and IVS types of YOO classification should be alerted of this potential transition. But the optimal timing of transition required more clinical studies.

[Preliminary Results of Single-cell Transcriptome Sequencing in Renal Arterial Lesions of Takayasu Arteritis].

Objective To explore the preliminary application of single-cell RNA sequencing (scRNA-seq) in the renal arterial lesions in Takayasu arteritis (TA) patients. Methods This study included 2 TA patients with renal artery stenosis treated by bypass surgery in the Department of Vascular Surgery,Beijing Hospital.The obtained 2 renal artery samples were digested with two different protocols (GEXSCOPE kit and self-made digestion liquid) before scRNA-seq and bioinformatics analysis. Results A total of 2920 cells were obtained for further analysis.After unbiased cluster analysis,2 endothelial cell subsets,2 smooth muscle cell subsets,1 fibroblast subset,2 mononuclear macrophage subsets,1 T cell subset,and 1 undefined cell subset were identified.Among them,the two subsets of smooth muscle cells were contractile and secretory,respectively.The results of scRNA-seq indicated that enzymatic hydrolysis with GEXSCOPE kit produced a large number of endothelial cells (57.46%) and a small number of immune cells (13.21%).However,immune cells (34.64%) were dominant in the cells obtained by enzymatic hydrolysis with self-made digestive liquid. Conclusion scRNA-seq can be employed to explore the cellular heterogeneity of diseased vessels in TA patients.Different enzymatic digestion protocols may impact the proportion of different cells.

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle.

In this study, we used the nanoparticle delivery system to reduce the side effect of conventional cancer treatment- radiation therapy and chemotherapy. We used rice husk silicon source mesoporous silica nanoparticle doped in Eu3+ and Gd3+ as the carrier in the delivery system and to enable fluorescence and MRI dual-imaging functions for follow-up therapy. In addition, we choose a popular seaweed extract-fucoidan was extracted from the same brown algae-Sargassum aquifolium collected from Taiwan-Pingtung-Kenting-Chuanfan Rock. In this research, we used acid hydrolysis to prepared two different molecular weight fucoidan, the small molecular fucoidan (Fus) as drug, and the molecular weight approximately 1 kDa fucoidan (Ful) as the nanoparticle gatekeeper, and as targeting molecule for overexpressed P-selectin on the surface of the metastatic tumors. The results of the cell cytotoxicity experiment showed that HCT116 cancer cells have a survival rate of approximately 58.12% when treated with 200 µg/mL fucoidan. Dual-imaging rice husk mesoporous silica nanoparticles (rMSN-EuGd) were modified with 1 kDa fucoidan (Ful) as the gatekeeper and target, and the small molecule fucoidan (Fus) was loaded into nanoparticles (Ful-Fus@rMSN-EuGd) at a concentration of 200 µg/mL. The HCT116 cancer cells had a survival rate of approximately 55.56%. The cell cytotoxicity experiment results show that Ful-Fus@rMSN-EuGd can improve the anticancer effect of fucoidan, and the nanoparticle drug delivery system using fucoidan as a drug, target, and gatekeeper was successfully synthesized.

Retrograde Recanalization for Proximal Occlusion of the Right Renal Artery through a Compensated Collateral Artery in a 10-year-old Patient.

BACKGROUND: To describe a retrograde recanalization for the proximal occluded lesion in right renal artery (RRA) in young patient with fibromuscular dysplasia (FMD). METHODS: A 10-year-old girl presented to our hospital with proximal RRA occlusion and refractory hypertension though she took anti-hypertension medicines. Her renin and aldosterone were beyond the normal level in both base state and excited state. Her glomerular filtration rate at right kidney was only 18.4 ml/min. Angiography revealed proximal RRA occlusion and a compensated collateral artery (CCA) from the infrarenal aorta to the RRA. She was thus diagnosed with focal FMD. A retrograde recanalization was performed through this CCA. RESULTS: Angioplasty and stenting were successfully performed to treat the proximal RRA occlusion. Postoperatively, the glomerular filtration rate in the right kidney improved. One-year follow-up revealed that, the blood pressure maintained at normal range without any antihypertensive agents. No other discomfort was complained. CONCLUSIONS: It is feasible to establish a working pathway with patient's compensated collateral artery to treat the renal artery occlusion.

Total Aortic and Branches Repair with Hybrid Therapy in the setting of Marfan Syndrome: A Case Report.

OBJECTIVE: Currently, no standard treatment has been established for the total lesion in patient with Marfan Syndrome (MFS). This case report aims to present a total aortic and branches repair with hybrid therapy in a young patient with MFS. METHODS: Clinical data including imaging manifestation, surgical document, and follow-up results were retrospectively collected and presented. RESULTS: A young patient with MFS underwent multi-stage endovascular aortic management and open surgical repair. On-the-table fenestration technique was applied to reconstruct the branches of the abdominal aorta. A bypass from superior mesenteric artery to celiac trunk was performed. A Bentall operation was conducted to repair his ascending aorta and aortic valves. Finally, in situ fenestration technique was adopted to recanalize the branches of aortic arch. The 18 month follow-up computed tomography angiography demonstrated patency of all the aorta branches. CONCLUSION: It may be feasible to perform the total aortic and branches repair with hybrid therapy in patients with MFS.

Aortic Intimo-intimal Intussusception: A Pooled Analysis of Published Reports.

AIM: Aortic intimo-intimal intussusception (AoII) is a rare manifestation of aortic dissection with high mortality. This study aimed to obtain a comprehensive understanding of AoII. METHODS: Three databases (PubMed, Scopus, Embase) were searched with predefined search terms ["intimal intussusception", "aortic intussusception", "(circumferential) AND (intimal dissection)" and "(circumferential) AND (aortic dissection)"]. Demographics, clinical manifestations, imaging methods, therapies, and follow-up data were recorded and analyzed. RESULTS: The literature search finally identified 81 papers comprising 87 patients (Mean age: 53.7 ± 14.9 years old; male: n = 63). According to morphologic criteria (orientation of AoII intimal flap), patients were divided into three groups: antegrade (n = 37), retrograde (n = 49) and bidirectional (n = 1) orientation. The most frequent symptoms in antegrade group were chest pain (62.2%), syncope (27%), and unconsciousness (21.6%), while in retrograde group, they were chest pain (71.4%), dyspnea (20.4%), and back pain (16.3%). Regarding applied imaging modalities, 67.5% of patients in antegrade group were diagnosed with≥2 methods, comparing with 87.7% in retrograde group. A total of 21 patients (24.1%) with AoII finally died, among which 13.8% (12/87) died before surgery. CONCLUSION: AoII is a rare form of aortic dissection with high mortality. Antegrade orientation of the intima flap was more accompanied with neurological disorders and asymmetric blood pressure, while retrograde orientation mostly manifested with aortic regurgitation. Application of multiple imaging examinations may detect this rare entity in time.

The Role of H2S in the Metabolism of Glucose and Lipids.

Glucose and lipids are essential elements for maintaining the body's homeostasis, and their dysfunction may participate in the pathologies of various diseases, particularly diabetes, obesity, metabolic syndrome, cardiovascular ailments, and cancers. Among numerous endogenous mediators, the gasotransmitter hydrogen sulfide (H2S) plays a central role in the maintenance of glucose and lipid homeostasis. Current evidence from both pharmacological studies and transgenic animal models suggest a complex relationship between H2S and metabolic dysregulation, especially in diabetes and obesity. This notion is achieved through tissue-specific expressions and actions of H2S on target metabolic and hormone organs including the pancreas, skeletal muscle, livers, and adipose. In this chapter, we will summarize the roles and mechanisms of H2S in several metabolic organs/tissues that are necessary for glucose and lipid metabolic homeostasis. In addition, future research directions and valuable therapeutic avenues around the pharmacological regulation of H2S in glycolipid metabolism disorder will be also discussed.

Role of nitroxyl (HNO) in cardiovascular system: From biochemistry to pharmacology.

Cardiovascular diseases are recognized to be a major cause of people morbidity and mortality. A host of stress signals contribute to the pathogenesis of cardiovascular disorders. Deficiency of hydrogen sulfide (H2S) or nitric oxide (NO) coordinately plays essential roles in the development of cardiovascular diseases. Recent studies have shown that interaction between the two gaseostransmitters, H2S and NO, may give rise to nitroxyl (HNO), one-electron-reduced product of NO. HNO is found to exhibit a variety of biological and pharmacological properties including positive inotropy and cardiovascular protective effects, etc. In this review, recent progresses regarding HNO generation, detection, biochemical and pharmacological functions are discussed.

Polysulfide and Hydrogen Sulfide Ameliorate Cisplatin-Induced Nephrotoxicity and Renal Inflammation through Persulfidating STAT3 and IKKß.

Cisplatin, a widely used chemotherapy for the treatment of various tumors, is clinically limited due to its extensive nephrotoxicity. Inflammatory response in tubular cells is a driving force for cisplatin-induced nephrotoxicity. The plant-derived agents are widely used to relieve cisplatin-induced renal dysfunction in preclinical studies. Polysulfide and hydrogen sulfide (H2S) are ubiquitously expressed in garlic, and both of them are documented as potential agents for preventing and treating inflammatory disorders. This study was designed to determine whether polysulfide and H2S could attenuate cisplatin nephrotoxicity through suppression of inflammatory factors. In renal proximal tubular cells, we found that sodium tetrasulfide (Na2S4), a polysulfide donor, and sodium hydrosulfide (NaHS) and GYY4137, two H2S donors, ameliorated cisplatin-caused renal toxicity through suppression of the massive production of inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Mechanistically, the anti-inflammatory actions of Na2S4 and H2S may be mediated by persulfidation of signal transducer and activator of transcription 3 (STAT3) and inhibitor kappa B kinase ß (IKKß), followed by decreased phosphorylation of STAT3 and IKKß. Moreover, the nuclear translocation of nuclear transcription factor kappa B (NF-κB), and phosphorylation and degradation of nuclear factor kappa B inhibitor protein alpha (IκBα) induced by cisplatin, were also mitigated by both polysulfide and H2S. In mice, after treatment with polysulfide and H2S donors, cisplatin-associated renal dysfunction was strikingly ameliorated, as evidenced by measurement of serum blood urea nitrogen (BUN) and creatinine levels, renal morphology, and the expression of renal inflammatory factors. Our present work suggests that polysulfide and H2S could afford protection against cisplatin nephrotoxicity, possibly via persulfidating STAT3 and IKKß and inhibiting NF-κB-mediated inflammatory cascade. Our results might shed light on the potential benefits of garlic-derived polysulfide and H2S in chemotherapy-induced renal damage.

Endovascular Repair of Complex Aortoiliac Aneurysm with the Sandwich Technique in Sixteen Patients.

BACKGROUND: This study aimed to evaluate the safety and efficiency of the sandwich technique in endovascular repair of complex aortoiliac aneurysm. METHODS: Sixteen patients (mean age 69.6 years, ranging from 58 to 78 years) with complex aortoiliac aneurysm were studied retrospectively from October 2013 to September 2017 in two vascular centers of teaching hospitals. Computed tomography angiography (CTA) was performed to make individual therapy. They were all performed endovascular repair with sandwich technique, including one with the sandwich, chimney, and fenestrated techniques during the same procedure. All patients were followed up at 1 month, 3 months, 6 months, 12 months, and yearly thereafter with X-ray, ultrasound, and/or CTA. RESULTS: The initial technical success was 81.25%, and the assisted technical success was 100%. At final angiography, little flow of a type I and a type III endoleak was found in two patients with observation. Two type II endoleaks were also detected. During the perioperative period, two patients suffered myocardial infarction. One pulmonary infection and one urinary infection happened. No death or cerebrovascular events occurred. During the follow-up (mean 18 months, ranging from 2 to 45 months), three stent occlusions were detected. One case got reintervened for his external iliac artery stent thrombosis in the first month postoperatively. The other two were under observation. A readmission happened to one man for his right brachial artery pseudoaneurysm in the third month postoperatively. One patient died of nonaneurysmal related reason in the eighth month. No aneurysmal related death, rupture, or new endoleak was found. No paralysis, claudication, or bowel ischemia was complained of. The primary patency of the preserved branches were 94.7%, 92.0%, 92.0%, 92.0%, 92.0% separately in first, sixth, 12th, 24th, and 36th month. CONCLUSIONS: For patients who are not candidates for open surgery or conventional endovascular repair with complex aortoiliac aneurysm, the sandwich technique is a feasible alternative to management.

Hydrogen Sulfide Prevents Elastin Loss and Attenuates Calcification Induced by High Glucose in Smooth Muscle Cells through Suppression of Stat3/Cathepsin S Signaling Pathway.

Vascular calcification can be enhanced by hyperglycemia. Elastin loss in tunica media promotes the osteogenic transformation of smooth muscle cells (SMCs) and involves arterial medial calcification (AMC) that is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes. Here, we tested whether hydrogen sulfide (H2S), an endogenous gaseous mediator, can prevent elastin loss and attenuate calcification induced by high glucose in SMCs. Calcification was induced by high glucose (4500 mg/L) in human aortic SMCs (HASMCs) under the condition of calcifying medium containing 10 mM ß-glycerophosphate (ß-GP). The experiments showed that NaHS (an H2S donor, 100 µM) mitigated the calcification of HASMCs treated with high glucose by decreasing calcium and phosphorus levels, calcium deposition and ALP activity and inhibited osteogenic transformation by increasing SMα-actin and SM22α, two phenotypic markers of smooth muscle cells, and decreasing core binding factor α-1 (Cbfα-1), a key factor in bone formation, protein expressions in HASMCs. Moreover, NaHS administration inhibited the activation of Stat3, cathepsin S (CAS) activity and its expression, but increased the level of elastin protein. Pharmacological inhibition or gene silencing Stat3 not only reversed elastin loss, but also attenuated CAS expression. Inhibition of CAS alleviated, while CAS overexpression exacerbated, elastin loss. Interestingly, overexpression of wild type (WT)-Stat3, but not its mutant C259S, elevated CAS protein expression and reduced elastin level. Moreover, NaHS induced S-sulfhydration in WT, but not in the C259S Stat3. These data suggest that H2S may directly regulate Cys259 residue in Stat3 and then impair its signaling function. Our data indicate that H2S may attenuate vascular calcification by upregulating elastin level through the inhibition of Stat3/CAS signaling.

Hydrogen Sulfide: Recent Progression and Perspectives for the Treatment of Diabetic Nephropathy.

Diabetic kidney disease develops in approximately 40% of diabetic patients and is a major cause of chronic kidney diseases (CKD) and end stage kidney disease (ESKD) worldwide. Hydrogen sulfide (H2S), the third gasotransmitter after nitric oxide (NO) and carbon monoxide (CO), is synthesized in nearly all organs, including the kidney. Though studies on H2S regulation of renal physiology and pathophysiology are still in its infancy, emerging evidence shows that H2S production by renal cells is reduced under disease states and H2S donors ameliorate kidney injury. Specifically, aberrant H2S level is implicated in various renal pathological conditions including diabetic nephropathy. This review presents the roles of H2S in diabetic renal disease and the underlying mechanisms for the protective effects of H2S against diabetic renal damage. H2S may serve as fundamental strategies to treat diabetic kidney disease. These H2S treatment modalities include precursors for H2S synthesis, H2S donors, and natural plant-derived compounds. Despite accumulating evidence from experimental studies suggests the potential role of the H2S signaling pathway in the treatment of diabetic nephropathy, these results need further clinical translation. Expanding understanding of H2S in the kidney may be vital to translate H2S to be a novel therapy for diabetic renal disease.

Hydrogen sulfide inhibits ATP-induced neuroinflammation and Aß1-42 synthesis by suppressing the activation of STAT3 and cathepsin S.

Neuroinflammation and excessive ß-amyloid1-42 (Aß1-42) generation contribute to the pathogenesis of Alzheimer's disease (AD). Emerging evidence has demonstrated that hydrogen sulfide (H2S), an endogenous gasotransmitter, produces therapeutic effects in AD; however, the underlying mechanisms remain largely elusive. In the present study, we investigated the effects of H2S on exogenous ATP-induced inflammation and Aß1-42 production in both BV-2 and primary cultured microglial cells and analyzed the potential mechanism(s) mediating these effects. Our results showed that NaHS, an H2S donor, inhibited exogenous ATP-stimulated inflammatory responses as manifested by the reduction of pro-inflammatory cytokines, ROS and activation of nuclear factor-κB (NF-κB) pathway. Furthermore, NaHS also suppressed the enhanced production of Aß1-42 induced by exogenous ATP, which is probably due to its inhibitory effect on exogenous ATP-boosted expression of amyloid precursor protein (APP) and activation of ß- and γ-secretase enzymes. Thereafter, we found that exogenous ATP-induced inflammation and Aß1-42 production requires the activation of signal transducer and activator of transcription 3 (STAT3) and cathepsin S (Cat S) as inhibition of the activity of either proteins attenuated the effect of exogenous ATP. Intriguingly, NaHS suppressed exogenous ATP-induced phosphorylation of STAT3 and the activation of Cat S. In addition, we observed that NaHS led to the persulfidation of Cat S at cysteine-25. Importantly, mutation of cysteine-25 into serine attenuated the activity of Cat S stimulated by exogenous ATP and subsequent inflammation and Aß1-42 production, indicating its involvement in H2S-mediated effect. Taken together, our data provide a novel understanding of H2S-mediated effect on neuroinflammation and Aß1-42 production by suppressing the activation of STAT3 and Cat S.

Higher Serum Fibroblast Growth Factor-23 Levels and the Risk of Stroke and Its Subtypes: Evidence From a Meta-Analysis of Prospective Studies.

BACKGROUND: Epidemiologic studies have indicated conflicting associations of fibroblast growth factor-23 (FGF23) with the risk of stroke. To this end, a meta-analysis of prospective studies was conducted to assess the association. METHODS: Relevant studies were identified by searching PubMed and Embase databases to March 23, 2018. Relative risks (RRs) with 95% confidence intervals (CIs) were combined with the fixed-effects model or random-effects model according to the degree of heterogeneity. Moreover, stratified analyses and sensitivity analysis were carried out for further analysis. RESULTS: Seven prospective studies involving 1988 stroke events among 18048 participants were eligible for our meta-analysis. The combined RRs for total stroke were 1.29 (95% CI: 1.10, 1.52) for the highest versus lowest category of FGF23, with low heterogeneity among studies (Pheterogeneity = 0.38, I2 = 6.1%). Stratified analyses showed that the combined RRs for ischemic stroke (IS) and hemorrhagic stroke (HS) risk were 1.12 (95% CI: 0.92, 1.37) and 2.63 (95% CI: 1.61, 4.30), respectively. In the stratification by geographic areas, the association between higher FGF23 and stroke was similar with studies performed in the United States (RR = 1.24, 95%CI: 1.03, 1.49) and Europe (RR = 1.88, 95%CI: 0.77, 4.55); however, only the results in the United States were statistically significant. Sensitivity analysis indicated the combined results were robust. CONCLUSIONS: Our meta-analysis showed that higher FGF23 levels were associated with an increased risk of stroke. The positive association consistently existed in HS rather than in IS. Further studies are required to confirm these causal associations and to investigate the mechanisms.

Human Umbilical Cord Blood CD34+Cells InducedAngiogenesis in Ischemic Limb of Mice.

Objective To observe the effect of the expanded human umbilical cord blood CD34+cells in ischemic limb of mice and analyse the relationship between the CD34+cells and angiogenesis. Methods Human umbilical cord blood was collected and CD34+cells were separated for expanding. Mice limbs ischemia models were established (n=15) and randomly divided into three groups:expanded CD34+cells group (n=5),fresh CD34+cells group (n=5),and control group(n=5). CD34+cells were detected by DiI dye tracing and antihuman nuclear antigen antibody(HNA) immunohistochemical staining. The improvement of blood reperfusion was evaluated by indicators including limb temperature,CD31 staining,and transforming growth factor-ß1 (TGF-ß1) mRNA expression. Results On days 14 (t=5.421,P=0.001;t=0.616,P=0.000) and 28(t=10.780,P=0.000; t=12.123,P=0.000),both expanded CD34+cells group and fresh CD34+cells group enjoyed better temperature improvement. Days 28 later,the vascular densities in the expanded CD34+cells group and the fresh CD34+cells group were 592.3±24.6 (t=26.386,P=0.000) and 530.7±25.5 (t=21.502,P=0.000),which were significantly higher than that in control group 219.7±19.9. The TGF-ß1 mRNA expression in the expanded CD34+cells group and the fresh CD34+cells group were (0.578±0.050) copies (t=12.376,P=0.000) and (0.504±0.080) copies (t=7.098,P=0.000),both over control group [(0.224±0.040)copies]. Conclusions In vitro culture of cord blood CD34+cells can emigrate to ischemic zone and induce angiogenesis to alleviate ischemia. Thus,it may provide a treatment option for lower limb ischemia.

Serum leptin levels may be correlated with cerebral infarction.

BACKGROUND: To investigate the relation between serum leptin levels and cerebral infarction (CI) by meta-analysis. MATERIALS AND METHODS: Scientific literature databases were searched for studies published in Chinese and English. After retrieving relevant articles through database searches and screening using predefined selection criteria, high-quality studies related to our research topic were selected for inclusion in this meta-analysis. All statistical analyses were conducted using Comprehensive Meta-Analysis 2.0 (CMA 2.0, Biostat Inc., Englewood, New Jersey, USA). RESULTS: The study results revealed that serum leptin levels were significantly higher in CI patients as compared to normal controls. The outcomes of subgroup analysis by ethnicity suggested that the serum leptin levels in CI patients were significantly higher than normal controls in both Asian and Caucasian populations. Further, subgroup analysis based on the detection method indicated that the serum leptin levels in CI patients were significantly higher compared with normal controls when measured by radioimmunoassay (RIA) but enzyme-linked immunosorbent assay (ELISA)-based measurements did not show such statistically significant differences. CONCLUSION: Our meta-analysis results suggest that serum leptin levels in CI patients may be closely correlated with CI risks.

Hydrogen sulfide inhibits opioid withdrawal-induced pain sensitization in rats by down-regulation of spinal calcitonin gene-related peptide expression in the spine.

Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we found that three hourly injections of DAMGO (a µ-opioid receptor agonist) followed by naloxone administration at the fourth hour significantly decreased rat paw nociceptive threshold, indicating the induction of withdrawal hyperalgesia. Application of NaHS (a hydrogen sulfide donor) together with each injection of DAMGO attenuated naloxone-precipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In SH-SY5Y neuronal cells, NaHS inhibited forskolin-stimulated cAMP production and adenylate cyclase (AC) activity. Moreover, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. Our data suggest that H2S prevents the development of opioid withdrawal-induced hyperalgesia via suppression of synthesis of CGRP in spine through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways.

Anti-inflammatory diterpenoids from the root bark of Acanthopanax gracilistylus.

Five new ent-pimarane (1-3, 7, and 8) and three new ent-kaurane diterpenoids (4-6) and a new oleanane triterpene acid (9), together with 22 known compounds, were isolated from the root bark of the medicinal herb Acanthopanax gracilistylus. The structures of 1-9 were established based on the interpretation of high-resolution MS and 1D- and 2D-NMR data. The absolute configurations of 7 and 11 were determined by single-crystal X-ray diffraction and electronic circular dichroism analysis. Compounds 7 and 8 represent rare naturally occurring structures based on the devinyl ent-pimarane skeleton. Compounds 3, 10, 14, 16, and 17 exhibited potent inhibitory effects on the release of interleukin-1ß (IL-1ß), interleukin-8 (IL-8), and tumor necrosis factor (TNF-α) in lipopolysaccharide-stimulated peripheral blood mononuclear cells.

1D Cu(I)-based chiral organic-inorganic hybrid material with second harmonic generation and circular polarized luminescence.

In recent years, organic-inorganic hybrid materials have demonstrated exceptional performance in nonlinear optics, attracting widespread attention. However, there are relatively few examples of coordination compounds synthesized with Cu as the metal center that exhibit excellent nonlinear optical properties. In this study, we successfully synthesized a pair of enantiomers named R/S-Cu2I2 by reacting chiral ligands with CuI. The crystal structure reveals a one-dimensional copper-iodide chain structure built by Cu2I2 clusters, and its ordered arrangement in space provides not only a strong second harmonic generation (SHG) signal (1.24 × KDP) but also a large birefringence (0.15@1064 nm). Under excitation at 395 nm, the crystals exhibit red fluorescence peaked at 675 nm. The CD spectra of R/S-Cu2I2 show a distinct mirror-symmetric Cotton effect, and their CPL signals are corresponding and opposite in the emission range, with a maximum glum of approximately ±2.5 × 10-3. Theoretical calculations using density functional theory were also carried out to enhance our understanding of the correlation between their structures and optical properties.

Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.