Prevalence and genotype distribution of human papillomavirus infection among 66000 women from 2014 to 2023 in the plateau region of Southwest China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

[Explorations in and Practice of Integrating Ideological and Political Theories Education in Stomatology Textbooks].

Stomatology textbooks are an important carrier of integrated ideological and political education. The preparation of textbooks for the stomatology specialty in the new era is an important issue of concern for administrators and teachers of higher education institutions. Integrating ideological and political education in the instruction and practice composnents of academic courses on stomatology is an important issue to be resolved. Herein, we introduced the significance of ideological and political education and elaborated on the method of integrating ideological and political education in stomatology courses and textbooks from the perspectives of curriculum design, textbook compilation, teacher training, teaching evaluation, etc. We analyzed the different ways of integrating ideological and political education in stomatology courses and textbooks from the perspectives of classroom instruction, clinical practice, campus culture, social activities, and some other aspects.

CiteSpace-Based Visualization Analysis of Forensic Research in China from 2010 to 2019.

OBJECTIVES: To analyze the research status of forensic medicine in China from 2010 to 2019, obtain the development trend of forensic medicine and explore the hotspots and research frontiers. METHODS: The forensic medical academic papers published on China National Knowledge Infrastructure (CNKI) database from 2010 to 2019 were collected. CiteSpace 5.7.R1, an information visualization analysis software, was used to analyze publication organizations, authors, keywords, and other elements. RESULTS: The majority of the research institutions were universities, provincial and ministerial scientific research and forensic institutions. Forensic pathology was still an important branch of forensic medicine and a popular research direction. The "polymorphism" and "Y chromosome" had been the research hotspots in recent years. "Medical damage" and "standard" were the most novel studies. CONCLUSIONS: In order to provide scientific basis and research direction for forensic research, this paper analyzes the cooperation network, research hotspots and research innovation in forensic research.

Enhancement of biotransformation of ginsenosides in white ginseng roots by aerobic co-cultivation of Bacillus subtilis and Trichoderma reesei.

In the present work, the biotransformation of ginsenosides in white ginseng roots was innovatively investigated using the aerobic fermentation by the co-cultivation of Bacillus subtilis and Trichoderma reesei. It is found that in the co-cultivation mode, the optimal nitrogen source was corn steep liquor, and the loading of ginseng powder and inoculation proportion of B. subtilis and T. reesei were 15 g/L and 1:4, respectively. The total ginsenoside yield and production of minor ginsenosides in the co-cultivation mode obviously enhanced in comparison to the monoculture mode. Meanwhile, the maximal total ginsenoside yield of 21.79% and high hydrolase activities were achieved using the staged inoculation at the inoculation proportion of 1:4 in the co-cultivation mode, the production of minor ginsenosides such as Rg3 and Rh1, Rh2 was significantly strengthened, and the pharmacological activities of the fermented solution obviously improved. The enhancement of ginsenoside transformation can be mainly attributed to hydrolysis of the produced hydrolases and metabolism of two probiotics. This result clearly reveals that using the staged inoculation in co-cultivation fermentation mode was favor of the ginsenoside biotransformation in ginseng due to non-synchronous cell growth and different metabolic pathways of both probiotics. This work can provide a novel method for enhancing ginsenoside transformation of ginseng.Key points• Co-cultivation fermentation significantly promoted ginsenoside biotransformation.• The staged inoculation in co-culture mode was an optimal operation method.• The pharmacological activity of the co-cultured solution was significantly enhanced.

Inner Ear Arginine Vasopressin-Vasopressin Receptor 2-Aquaporin 2 Signaling Pathway Is Involved in the Induction of Motion Sickness.

It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus- or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness. SIGNIFICANCE STATEMENT: Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness.

Comparative Efficacy of Drugs for the Treatment of Chronic Constipation: Quantitative Information for Medication Guidelines.

BACKGROUND: Quantitative information is scarce with regard to guidelines for currently prescribed medications for constipation. Furthermore, these guidelines do not reflect the differences in the number of bowel movements caused by each drug. GOALS: In this study, we used a model-based meta-analysis to quantitatively estimate the deviations from the baseline number of spontaneous bowel movements (SBMs) and complete spontaneous bowel movements (CSBMs) associated with pharmacotherapy for chronic constipation to bridge the knowledge gap in the guidelines for current medications. STUDY: A comprehensive survey was conducted using literature databases. In this study, we also included randomized placebo-controlled trials on chronic constipation. Pharmacodynamic models were established to describe the time course of the numbers of SBMs and CSBMs produced by each drug. RESULTS: Data from 20 studies (comprising 9998 participants and 8 drugs) were used to build this model. The results showed that bisacodyl had the greatest effect on increasing the frequency of bowel movements, whereas plecanatide yielded the lowest increase in the number of SBMs and CSBMs. After eliminating the placebo effect, the maximal increase in bowel movement frequency associated with bisacodyl was 6.8 for SBMs (95% confidence interval: 6.1-7.6) and 4.7 for CSBMs (95% confidence interval: 4.3-5.1) per week. These numbers are ∼4 times higher than the number of bowel movements produced by plecanatide. The change in the frequency of SBMs and CSBMs for other drugs, such as sodium picosulfate, velusetrag, linaclotide, elobixibat, lubiprostone, and prucalopride, was similar. The highest increases in the frequency of SBM and CSBM were 2.5 to 4 and 1 to 2.1 per week, respectively. Bisacodyl had the most noticeable loss of efficacy between week 1 and week 4; it reduced the frequencies of SBMs and CSBMs by 2.3 and 2.2, respectively. By contrast, the changes in the frequencies of SBMs and CSBMs were not as great with other drugs. CONCLUSIONS: The data provided in this study may be a valuable supplement to the medication guidelines for the treatment of chronic constipation.

The rearranged mitochondrial genome of Podagrion sp. (Hymenoptera: Torymidae), a parasitoid wasp of mantis.

The complete sequence of the mitochondrial genome of Podagrion sp. (Hymenoptera: Torymidae) is described. The mitogenome was 15,845 bp in size, and contained typical sets of mitochondrial genes. The base composition of the Podagrion sp. mitogenome was also biased toward A + T bases (81.8%). The mitochondrial genome of Podagrion sp. has a weak AT skew (0.07) and a strong GC skew (-0.26). Podagrion sp. exhibits a novel rearrangement compared with the ancestral order, including six protein-coding genes (nad3, cox3, atp6, atp8, cox2 and cox1), which have inverted to the minor strand from the major strand. The A + T-rich region of Podagrion sp., which is located between trnN and trnI, have five tandem repeats. The apomorphic rearrangements, including the conserved block "cox3-atp6-atp8-cox2-cox1-nad5-nad4-nad4l-nad6-cob" and the special locations of trnV and trnA, were mapped onto the phylogeny of Proctotrupomorpha.

Effect of Cognitive Behavioral Therapy on Improving the Cognitive Function in Major and Minor Depression.

The aim of this study was to investigate the effectiveness of cognitive behavioral therapy (CBT) on improving the cognitive function in minor depression (MiD) and major depression (MaD). The study will constitute a placebo-controlled single-blind parallel-group randomized controlled trial. The selected participants will be randomly allocated into one of two parallel groups with a 1:1 ratio: the CBT-based group and the general health education group. CBT significantly alleviated depressive symptoms of MiD and MaD at 12 weeks (p < 0.001), and the treatment effect was maintained for at least 12 months (p < 0.001). Interestingly, CBT significantly promotes more cognitive function of MiD and partial cognitive function of MaD at 12 weeks in the intervention group than in the control group (p < 0.01). CBT can alleviate depressive symptoms of both minor and MaDs. The effectiveness of CBT is different on improving the cognitive function in MiD and MaD.

9-PAHSA promotes browning of white fat via activating G-protein-coupled receptor 120 and inhibiting lipopolysaccharide / NF-kappa B pathway.

Browning of white adipose tissue is a novel mechanism to counteract obesity in view of its thermogenic activity. Activation of G-protein-coupled receptor 120 (GPR120) can promote the browning of white fat. 9-PAHSA, an endogenous mammalian lipid, which is acting as the ligand of GPR120 to enhance glucose uptake and exert anti-inflammatory effect. In the study, we would like to investigate the biological effects of 9-PAHSA on adipocyte browning. Here, we show that 9-PAHSA induces browning of 3T3-L1 adipocytes via enhanced expression of brown fat specific genes. 9-PAHSA-induced browning in white adipocytes of WT mice and ob/ob mice was investigated by determining expression levels of brown adipocyte-specific genes/proteins by quantitative real-time polymerase chain reaction analysis, immunoblot analysis and immunochemical staining. The effects of 9-PAHSA on brown fat markers in 3T3-L1 cells were decreased when GPR120 gene was silenced. To investigate the molecular mechanism of 9-PAHSA on adipocyte browning, lipopolysaccharide (LPS)-induced inflammatory model was conducted. 9-PAHSA treatment abolished LPS-induced NF-kappa B (NF-κB) activation and inflammatory cytokine secretion. But these anti-inflammatory effects of 9-PAHSA were attenuated by GPR120 knockdown. Our finding demonstrated that the browning of adipocyte was induced by 9-PAHSA through activating GPR120 and inhibiting the LPS/NF-κB pathway. This promising result will help to reveal the potential pathogenesis of obesity.

Adipocyte differentiation is regulated by mitochondrial trifunctional protein α-subunit via sirtuin 1.

Mitochondrial trifunctional protein α-subunit (MTPα) is involved in the fatty acid ß-oxidation (FAO) pathway. Two MTPα activities, 3-hydroxyacyl-CoA dehydrogenase and long-chain hydratase, have been linked with the occurrence and development of obesity and obesity-related disorders. These activities catalyze two steps in the FAO pathway (the second and third reactions). However, the role of MTPα in the pathogenesis of obesity has not been evaluated, and the functional role of MTPα in adipocyte differentiation has not been determined. Here, we analyzed the functional role of MTPα using in vitro and in vivo models of adipogenesis. MTPα expression was upregulated during the differentiation of 3T3-L1 preadipocyte cells into adipocytes. MTPα gene silencing stimulated peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT-enhancer-binding protein alpha(C/EBPα) expression, which promoted adipocyte differentiation. By contrast, MTPα overexpression blocked adipogenesis in 3T3-L1 cells. Further analysis showed that MTPα positively regulated sirtuin 1 (SIRT1). Injection of preadipocytes overexpressing MTPα into athymic mice significantly impaired de novo fat pad formation compared with that of the control, and furthermore MTPα knockdown enhances fat pad formation at a time point earlier than 5-week, such as week-2 and week-3, when the control fat pad is not fully developed. In summary, our data indicate that MTPα is a novel factor that negatively regulates adipocyte differentiation. We propose a pathway in which MTPα inhibits adipogenesis by promoting SIRT1 expression, which represses PPARγ and attenuates adipogenesis.

Orexin-A increases the activity of globus pallidus neurons in both normal and parkinsonian rats.

Orexin is a member of neuropeptides which was first identified in the hypothalamus. The globus pallidus is a key structure in the basal ganglia, which is involved in both normal motor function and movement disorders. Morphological studies have shown the expression of both OX1 and OX2 receptors in the globus pallidus. Employing single unit extracellular recordings and behavioural tests, the direct in vivo electrophysiological and behavioural effects of orexin-A in the globus pallidus were studied. Micro-pressure administration of orexin-A significantly increased the spontaneous firing rate of pallidal neurons. Correlation analysis revealed a negative correlation between orexin-A induced excitation and the basal firing rate. Furthermore, application of the specific OX1 receptor antagonist, SB-334867, decreased the firing rate of pallidal neurons, suggesting that endogenous orexinergic systems modulate the firing activity of pallidal neurons. Orexin-A increased the excitability of pallidal neurons through both OX1 and OX2 receptors. In 6-hydroxydopamine parkinsonian rats, orexin-A-induced increase in firing rate of pallidal neurons was stronger than that in normal rats. Immunostaining revealed positive OX1 receptor expression in the globus pallidus of both normal and parkinsonian rats. Finally, postural test showed that unilateral microinjection of orexin-A led to contralateral deflection in the presence of systemic haloperidol administration. Further elevated body swing test revealed that pallidal orexin-A and SB-334867 induced contralateral-biased swing and ipsilateral-biased swing respectively. Based on the electrophysiological and behavioural findings of orexin-A in the globus pallidus, the present findings may provide a rationale for the pathogenesis and treatment of Parkinson's disease.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate firing of globus pallidus neurons in vivo.

The globus pallidus plays a significant role in motor control under both health and pathological states. Recent studies have revealed that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels occupy a critical position in globus pallidus pacemaking activity. Morphological studies have shown the expression of HCN channels in the globus pallidus. To investigate the in vivo effects of HCN channels in the globus pallidus, extracellular recordings and behavioral tests were performed in the present study. In normal rats, micro-pressure ejection of 0.05mM ZD7288, the selective HCN channel blocker, decreased the frequency of spontaneous firing in 21 out of the 40 pallidal neurons. The average decrease was 50.4±5.4%. Interestingly, in another 18 out of the 40 pallidal neurons, ZD7288 increased the firing rate by 137.1±27.6%. Similar bidirectional modulation on the firing rate was observed by a higher concentration of ZD7288 (0.5mM) as well as another HCN channel blocker, CsCl. Furthermore, activation of HCN channels by 8-Br-cAMP increased the firing rate by 63.0±9.3% in 15 out of the 25 pallidal neurons and decreased the firing rate by 46.9±9.4% in another 8 out of the 25 pallidal neurons. Further experiments revealed that modulation of glutamatergic but not GABAergic transmission may be involved in ZD7288-induced increase in firing rate. Consistent with electrophysiological results, further studies revealed that modulation of HCN channels also had bidirectional effects on behavior. Taken together, the present studies suggest that HCN channels may modulate the activity of pallidal neurons by different pathways in vivo.

[Effect of Modified Hangqi Chifeng Decoction Containing Serum on the Expression of Col IV, MMP-2, and TIMP-2 in Glomerular Mesangial Cells Induced by LPS].

OBJECTIVE: To explore the effect of Modified Hangqi Chifeng Decoction (MHCD) on levels of collagen type IV (Col IV), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) in extracellular matrix (ECM) of glomerular mesangial cells (GMCs) in LPS induced mice. METHODS: Normal serum and telmisartan, high, medium, low dose MHCD containing serums were prepared by using serum pharmacology method. GMCs were cultured in vitro. The proliferation of mesangial cells were induced using LPS as stimulating factor. GMCs were divided into six groups, i.e., the normal group, the model group, the telmisartan group, high, medium and low dose MHCD groups. Col IV content in the supernatant of mesangial cells was detected using ELISA. Protein expressions of MMP-2 and TIMP-2 were detected using Western blot. RESULTS: Compared with the normal group, Col IV content obviously increased in the model group after 72-h LPS stimulation; protein expressions of MMP-2 and TIMP-2 were obviously up-regulated, and MMP-2/TIMP-2 ratio was down-regulated in the model group (P < 0.01). Compared with the model group, Col IV content obviously decreased in high and medium dose MHCD groups and the telmisartan group (P < 0.01); protein expressions of MMP-2 were obviously down-regulated in medium and low dose MHCD groups (P < 0.01, P < 0.05); the protein expression of TIMP-2 was obviously down-regulated in high, medium, low dose MHCD groups and the telmisartan group (P < 0.01). The pro- tein expression of TIMP-2 was obviously lower in the high dose MHCD group than in the low dose MHCD group (P < 0.01). MMP-2/TIMP-2 ratio was obviously up-regulated in the telmisartan group, high and medium dose MHCD groups (P < 0.01). CONCLUSION: MHCD could regulate disordered MMP-2/TIMP-2 ratio in LPS induced ECM, inhibit excessive production of Col IV in ECM, promote the degradation of ECM, reduce the accumulation of ECM, thereby, delaying the process of glomerular sclerosis.

[Anti-renal Fibrosis Mechanism of Modified Huangqi Chifeng Decoction Based on TGF-p1/Smad Signal Pathway].

Objective To observe the effect of Modified Huangqi Chifeng Decoction (MHCD) on TGF-ß1/Smad signal pathway, and to explore its anti-renal fibrosis mechanism. Methods Adopting ser- um pharmacology method, rats were intragastrically administered with MHCD and telmisartan to prepare drug containing serum. Mouse mesangial cells were cultured in vitro, using lipopolysaccharides (LPS) as stimulating factor. The cells were divided into six groups, i.e., the normal group, the model group, the telmisartan group, high, medium and low dose MHCD groups. The cell supernatant was collected in each group after mouse mesangial cells were intervened by drug containing serum for 72 h. Contents of laminin (LN) and fibronectin (FN) were measured using ELISA. Protein expression levels of TGF-P, , p-Smad2/3, Smad7, and connective tissue growth factor (CTGF) were detected using Western blot. Results (1) Compared with the normal group, contents of LN and FN in supernatant significantly increased in the model group (P <0. 01). Compared with the model group, contents of LN and FN were significantly reduced in the telmisartan group and the medium dose MHCD group (P <0. 05, P <0. 01). FN content in su- pernatant significantly decreased in the low dose MHCD group (P <0. 01). (2) Compared with the normal group, protein expressions of TGF-ß1 , p-Smad2/3, and CTGF were significantly increased, Smad7 protein expression significantly decreased in the model group, with statistical difference (P <0. 01). Compared with the model group, protein expressions of TGF-ß1 and CTGF significantly decreased in the telmisartan group and 3 MHCD groups (P <0. 01 , P <0. 05) ; protein expression of p-Smad23 significantly decreased in the telmisartan group, high and medium dose MHCD groups (P <0.01); Smad7 protein expression were significantly increased in high and medium dose MHCD groups (P <0. 05). Conclusion MHCD could inhibit increased inflammatory factors induced secretion of extracellular matrix in glomerular mesangial cells, and restrain excessive activation of TGF-ß1/Smad signal pathways, which might be one of its anti-renal fibrosis mechanisms.

[Exploration of visual check approaches in clinical data management].

Due to a great amount of data in clinical trials, the data cleansing needs to adopt a variety of measures, including the latest developed visual check approach. According to the different types of clinical data and the different stages in the course of clinical data management, this study reviews 8 types of visual graphics that show the relevance and trend among the data. The series of graphics can rapidly detect abnormal data, monitor clinical research in real-time, make the data management process much easier and improve the clinical trial efficiency and data quality.

[Comparison of paper and electronic data management in clinical trials].

Electronic case report forms (eCRFs) instead of the traditional paper case report forms (pCRFs) are increasingly used by investigators and sponsors of clinical research. We include a total of 14 phase III studies (8 pCRF, 6 eCRF) to compare paper and electronic data documentation both quantitatively and qualitatively in clinical studies. The result suggests that adaptions of electronic data capture (EDC) in clinical trials have the advantages in optimization of data capture process, improvement of data quality and earlier clinical decision compared to paper-based methods. Furthermore, the successful implementation of EDC requires accouplements with corresponding data management processes and reallocation of resources.

[Quality control of clinical data management based on EDC].

With the wide application of electronic data management (EDC), the data management is shifting to a new mode. In order to recognize the advantages of EDC, we choose 20 representative registered clinical trials, which involve 5 404 subjects and 321 sites. We found that EDC has many beneficial impacts on the course of clinical trial data management, including the process of data collection, data cleaning, data quality control and clinical trial decision-making. The result also provides a reference for the adoption of EDC in clinical trials.

The role of cystathionine ß-synthase in cancer.

Cystathionine ß-synthase (CBS) occupies a key position as the initiating and rate-limiting enzyme in the sulfur transfer pathway and plays a vital role in health and disease. CBS is responsible for regulating the metabolism of cysteine, the precursor of glutathione (GSH), an important antioxidant in the body. Additionally, CBS is one of the three enzymes that produce hydrogen sulfide (H2S) in mammals through a variety of mechanisms. The dysregulation of CBS expression in cancer cells affects H2S production through direct or indirect pathways, thereby influencing cancer growth and metastasis by inducing angiogenesis, facilitating proliferation, migration, and invasion, modulating cellular energy metabolism, promoting cell cycle progression, and inhibiting apoptosis. It is noteworthy that CBS expression exhibits complex changes in different cancer models. In this paper, we focus on the CBS synthesis and metabolism, tissue distribution, potential mechanisms influencing tumor growth, and relevant signaling pathways. We also discuss the impact of pharmacological CBS inhibitors and silencing CBS in preclinical cancer models, supporting their potential as targeted cancer therapies.

Exploring the impact of hydrogen sulfide on hematologic malignancies: A review.

Hydrogen sulfide (H2S) is one of the three most crucial gaseous messengers in the body. The discovery of H2S donors, coupled with its endogenous synthesis capability, has sparked hope for the treatment of hematologic malignancies. In the last decade, the investigation into the impact of H2S has expanded, particularly within the fields of cardiovascular function, inflammation, infection, and neuromodulation. Hematologic malignancies refer to a diverse group of cancers originating from abnormal proliferation and differentiation of blood-forming cells, including leukemia, lymphoma, and myeloma. In this review, we delve deeply into the complex interrelation between H2S and hematologic malignancies. In addition, we comprehensively elucidate the intricate molecular mechanisms by which both H2S and its donors intricately modulate the progression of tumor growth. Furthermore, we systematically examine their impact on pivotal aspects, encompassing the proliferation, invasion, and migration capacities of hematologic malignancies. Therefore, this review may contribute novel insights to our understanding of the prospective therapeutic significance of H2S and its donors within the realm of hematologic malignancies.

microRNA 21-mediated suppression of Sprouty1 by Pokemon affects liver cancer cell growth and proliferation.

Transcriptional repressor Pokemon is a critical factor in embryogenesis, development, cell proliferation, differentiation, and oncogenesis, thus behaving as an oncogene. Oncomine database suggests a potential correlation between the expressions of Pokemon and Sprouty1. This study investigated the regulatory role of Pokemon in Sprouty1 expression and the effect on liver cancer cell growth and proliferation, revealing a novel miR-21-mediated regulatory circuit. In normal (HL-7702) and cancer (QGY-7703) liver cell lines, Sprouty1 expression is inversely correlated with Pokemon levels. Targeted expression or siRNA-mediated silencing showed that Pokemon is a repressor of Sprouty1 expression at both mRNA and protein levels, but Pokemon cannot affect the promoter activity of Sprouty1. Sprouty1 is a target of miR-21 and interestingly, we found that miR-21 is up-regulated by Pokemon in liver cancer cells. Luciferase reporter assays showed that Pokemon up-regulated miR-21 transcription in a dose-dependent manner, and ChIP assay exhibited a direct binding of Pokemon to the miR-21 promoter at -747 to -399 bp. Site-directed mutagenesis of the GC boxes at -684 to -679 bp and -652 to -647 bp of miR-21 promoter abolished the regulatory activity by Pokemon. Furthermore, we found that the modulation of Pokemon and miR-21 expression affected the growth and proliferation of liver cancer cells QGY-7703. In summary, our findings demonstrate that Pokemon suppresses Sprouty1 expression through a miR-21-mediated mechanism, affecting the growth and proliferation of liver cancer cells. This study recognized miR-21 and Sprouty1 as novel targets of the Pokemon regulatory network.