Role of hydrogen sulfide-microRNA crosstalk in health and disease.

The mutual regulation between hydrogen sulfide (H2S) and microRNA (miRNA) is involved in the development of many diseases, including cancer, cardiovascular disease, inflammatory disease, and high-risk pregnancy. Abnormal expressions of endogenous H2S-producing enzyme and miRNA in tissues and cells often indicate the occurrence of diseases, so the maintenance of their normal levels in the body can mitigate damages caused by various factors. Many studies have found that H2S can promote the migration, invasion, and proliferation of cancer cells by regulating the expression of miRNA, while many H2S donors can inhibit cancer progression by interfering with the proliferation, apoptosis, cell cycle, metastasis, and angiogenesis of cancer cells. Furthermore, the mutual regulation between H2S and miRNA can also prevent cell injury in cardiovascular disease and inflammatory disease through anti-inflammation, anti-oxidation, anti-apoptosis, and pro-autophagy. In addition, H2S can promote angiogenesis and relieve vasoconstriction by regulating the expression of miRNA, thereby improving fetal growth in high-risk pregnancy. In this review, we discuss the mechanism of mutual regulation between H2S and miRNA in various diseases, which may provide reliable therapeutic targets for these diseases.

Emerging roles of hydrogen sulfide in colorectal cancer.

Hydrogen sulfide (H2S), an endogenous gasotransmitter, plays a key role in several critical physiological and pathological processes in vivo, including vasodilation, anti-infection, anti-tumor, anti-inflammation, and angiogenesis. In colorectal cancer (CRC), aberrant overexpression of H2S-producing enzymes has been observed. Due to the important role of H2S in the proliferation, growth, and death of cancer cells, H2S can serve as a potential target for cancer therapy. In this review, we thoroughly analyzed the underlying mechanism of action of H2S in CRC from the following aspects: the synthesis and catabolism of H2S in CRC cells and its effect on cell signal transduction pathways; the inhibition effects of exogenous H2S donors with different concentrations on the growth of CRC cells and the underlying mechanism of H2S in garlic and other natural products. Furthermore, we elucidate the expression characteristics of H2S in CRC and construct a comprehensive H2S-related signaling pathway network, which has important basic and practical significance for promoting the clinical research of H2S-related drugs.

Hydrogen Sulfide in Musculoskeletal Diseases: Molecular Mechanisms and Therapeutic Opportunities.

SIGNIFICANCE: Musculoskeletal diseases seriously affect global health, but their importance is greatly underestimated. These diseases often afflict the elderly, leading to disability, paralysis, and other complications. Hydrogen sulfide (H2S) plays an important role in the occurrence and development of musculoskeletal diseases, which may have potential ther-apeutic significance for these diseases. RECENT ADVANCES: Recently, it has been found that many musculoskeletal diseases, such as osteoporosis, periodontitis, muscle atrophy, muscle ischemia-reperfusion injury, mus-cle contraction under high fever, arthritis, and disc herniation, can be alleviated by sup-plementing H2S. H2S may be conducive to the development of multiple myeloma. The mechanism of H2S effect on the musculoskeletal system has been elucidated. A variety of H2S donors and nano-delivery systems provide prospects for H2S-based therapies. CRITICAL ISSUES: Related research remains at the level of cell or animal experiments, and clinical research is lacking. The role of H2S in more musculoskeletal disorders remains largely unknown. The importance of musculoskeletal diseases has not been widely con-cerned. Targeted delivery of H2S remains a challenging task. FUTURE DIRECTION: Develop therapeutic drugs for musculoskeletal diseases based on H2S and test their safety, efficacy, and tolerance. Explore the combination of current musculo-skeletal disease drugs with H2S releasing components to improve efficacy and avoid side effects. Carry out relevant clinical trials to verify the possibility of its widespread use.

Recent advances in the role of hydrogen sulfide in age-related diseases.

In recent years, the impact of age-related diseases on human health has become increasingly severe, and developing effective drugs to deal with these diseases has become an urgent task. Considering the essential regulatory role of hydrogen sulfide (H2S) in these diseases, it is regarded as a promising target for treatment. H2S is a novel gaseous transmitter involved in many critical physiological activities, including anti-oxidation, anti-inflammation, and angiogenesis. H2S also regulates cell activities such as cell proliferation, migration, invasion, apoptosis, and autophagy. These regulatory effects of H2S contribute to relieving and treating age-related diseases. In this review, we mainly focus on the pathogenesis and treatment prospects of H2S in regulating age-related diseases.

Role of hydrogen sulfide in dermatological diseases.

Hydrogen sulfide (H2S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H2S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H2S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H2S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H2S in normal skin, the role of altering H2S metabolism in dermatological diseases, and the therapeutic potential of diverse H2S donors for the treatment of dermatological diseases.

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.

Novel Small Molecule Matrix Screening for Simultaneous MALDI Mass Spectrometry Imaging of Multiple Lipids and Phytohormones.

Most of the traditional matrices cannot simultaneously image multiple lipids and phytohormones, so screening and discovery of novel matrices stand as essential approaches for broadening the application scope of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). In this work, 12 organic small molecule compounds were comprehensively screened and investigated as potential MALDI matrices for simultaneous imaging analysis of various lipids and phytohormones. In the positive ionization mode, p-nitroaniline, m-nitroaniline, and 2-aminoterephthalic acid displayed good performance for the highly sensitive detection of lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), and triacylglycerols (TGs). Furthermore, p-nitroaniline possessed excellent characteristics of strong ultraviolet absorption and homogeneous cocrystallization, making it a desirable matrix for MALDI-MSI analysis of eight plant hormones. Compared with conventional matrices (2,5-dihydroxybenzoic acid (DHB), α-cyano-4-hydroxycinnamic acid (CHCA), and 9-aminoacridine (9-AA), the use of p-nitroaniline resulted in higher ionization efficiency, superior sensitivity, and clearer imaging images in dual polarity mode. Our research offers valuable guidance and new ideas for future endeavors in matrix screening.

The potential role of hydrogen sulfide in cancer cell apoptosis.

For a long time, hydrogen sulfide (H2S) has been considered a toxic compound, but recent studies have found that H2S is the third gaseous signaling molecule which plays a vital role in physiological and pathological conditions. Currently, a large number of studies have shown that H2S mediates apoptosis through multiple signaling pathways to participate in cancer occurrence and development, for example, PI3K/Akt/mTOR and MAPK signaling pathways. Therefore, the regulation of the production and metabolism of H2S to mediate the apoptotic process of cancer cells may improve the effectiveness of cancer treatment. In this review, the role and mechanism of H2S in cancer cell apoptosis in mammals are summarized.

Endogenous hydrogen sulfide inhibition suppresses tumor growth by promoting apoptosis and pyroptosis in esophageal cancer cells.

BACKGROUND: Hydrogen sulfide (H2S) has been identified as the third gaseous signaling molecule. Endogenous H2S plays a key role in the progression of various types of cancer. However, the effect of endogenous H2S on the growth of esophageal cancer (EC) remains unknown. METHODS: In this study, three kinds of H2S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor of cystathionine-ß-synthase), and L-aspartic acid (L-Asp, inhibitor of 3-mercaptopyruvate sulfurtransferase) were used to determine the role of endogenous H2S in the growth of EC9706 and K450 human EC cells. RESULTS: The results indicated that the combination (PAG+AOAA+L-Asp) group showed higher inhibitory effects on the viability, proliferation, migration, and invasion of EC cells than PAG, AOAA, and L-Asp group. Inhibition of endogenous H2S promoted apoptosis via activation of mitogen-activated protein kinase pathway in EC cells. Endogenous H2S suppression triggered pyroptosis of EC cells by activating reactive oxygen species-mediated nuclear factor-κB signaling pathway. In addition, the combine group showed its more powerful growth-inhibitory effect on the growth of human EC xenograft tumors in nude mice without obvious toxicity. CONCLUSION: Our results indicate that inhibition of endogenous H2S production can significantly inhibit human EC cell growth via promotion of apoptosis and pyroptosis. Endogenous H2S may be a promising therapeutic target in EC cells. Novel inhibitors for H2S-producing enzymes can be designed and developed for EC treatment.

Nanotechnology prospects in brain therapeutics concerning gene-targeting and nose-to-brain administration.

Neurological diseases are one of the most pressing issues in modern times worldwide. It thus possesses explicit attention from researchers and medical health providers to guard public health against such an expanding threat. Various treatment modalities have been developed in a remarkably short time but, unfortunately, have yet to lead to the wished-for efficacy or the sought-after clinical improvement. The main hurdle in delivering therapeutics to the brain has always been the blood-brain barrier which still represents an elusive area with lots of mysteries yet to be solved. Meanwhile, nanotechnology has emerged as an optimistic platform that is potentially holding the answer to many of our questions on how to deliver drugs and treat CNS disorders using novel technologies rather than the unsatisfying conventional old methods. Nanocarriers can be engineered in a way that is capable of delivering a certain therapeutic cargo to a specific target tissue. Adding to this mind-blowing nanotechnology, the revolutionizing gene-altering biologics can have the best of both worlds, and pave the way for the long-awaited cure to many diseases, among those diseases thus far are Alzheimer's disease (AD), brain tumors (glioma and glioblastoma), Down syndrome, stroke, and even cases with HIV. The review herein collects the studies that tested the mixture of both sciences, nanotechnology, and epigenetics, in the context of brain therapeutics using three main categories of gene-altering molecules (siRNA, miRNA, and CRISPR) with a special focus on the advancements regarding the new favorite, intranasal route of administration.

[Research progress on chemical structures and pharmacological effects of natural cytisine and its derivatives].

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.

Inhibition of endogenous hydrogen sulfide production suppresses the growth of nasopharyngeal carcinoma cells.

Hydrogen sulfide (H2 S) has been widely recognized as one of gasotransmitters. Endogenous H2 S plays a crucial role in the progression of cancer. However, the effect of endogenous H2 S on the development of nasopharyngeal carcinoma (NPC) is still unknown. In this study, aminooxyacetic acid (AOAA, an inhibitor of cystathionine-ß-synthase), dl-propargylglycine (PAG, an inhibitor of cystathionine-γ-lyase), and l-aspartic acid (l-Asp, an inhibitor of 3-mercaptopyruvate sulfurtransferase) were adopted to detect the role of endogenous H2 S in NPC growth. The results indicated that the combine (PAG + AOAA + l-Asp) group had higher inhibitory effect on the growth of NPC cells than the PAG, AOAA, and l-Asp groups. There were similar trends in the levels of apoptosis and reactive oxygen species (ROS). In addition, the combine group exhibited lower levels of phospho (p)-extracellular signal-regulated protein kinase but higher expressions of p-p38 and p-c-Jun N-terminal kinase than those in the AOAA, PAG, and l-Asp groups. Furthermore, the combine group exerted more potent inhibitory effect on NPC xenograft tumor growth without obvious toxicity. In summary, suppression of endogenous H2 S generation could dramatically inhibit NPC growth via the ROS/mitogen-activated protein kinase pathway. Endogenous H2 S may be a novel therapeutic target in human NPC cells. Effective inhibitors for H2 S-producing enzymes could be designed and developed for NPC treatment.

Hydrogen sulfide and its donors: Novel antitumor and antimetastatic agents for liver cancer.

Hepatocellular carcinoma (HCC) is the sixth most frequent human cancer and the world's third most significant cause of cancer mortality. HCC treatment has recently improved, but its mortality continues to increase worldwide due to its extremely complicated and heterogeneous genetic abnormalities. After nitric oxide (NO) and carbon monoxide (CO), the third gas signaling molecule discovered is hydrogen sulfide (H2S), which has long been thought to be a toxic gas. However, numerous studies have proven that H2S plays many pathophysiological roles in mammals. Endogenous or exogenous H2S can decrease cell proliferation, promote apoptosis, block cell cycle, invasion and migration through various cellular signaling pathways. This review analyzes and discusses the recent literature on the function and molecular mechanism of H2S and H2S donors in HCC, so as to provide convenience for the scientific research and clinical application of H2S in the treatment of liver cancer.

Investigation of the Internal Conditions of 213 Reprocessed Endoscopic Channels.

BACKGROUND AND AIMS: Studies have indicated that endoscope reprocessing failure might be attributed to internal damage or residual liquid in endoscopes. However, large-sample survey data on the internal conditions of endoscopic channels after reprocessing are lacking. This study used a borescope to investigate the internal cleanliness and damage of 213 endoscopic biopsy channels after reprocessing at the endoscopy center of the First Affiliated Hospital of Nanchang University, provided in theoretical basis for the efficacy of endoscope reprocessing and maintenance. METHODS: A borescope was used to observe and analyze the inside of the endoscopic biopsy channel of 213 reprocessed endoscopes (in accordance with the Chinese health industry standard "Regulation for cleaning and disinfection technique of flexible endoscope (WS 507-2016). Each endoscope was observed for at least 10 minutes, and the results were recorded and evaluated by 5 researchers independently. RESULTS: In all, 2504 images and 109 videos were recorded, and abnormal findings were classified into 10 categories: scratches (91.5%, 195/213), scratches with adherent peel (46.0%, 98/213), discolored areas (49.3%, 105/213), transparent drops (28.2%, 60/213), milky drops (23.9%, 51/213), white particles (46.9%, 100/213), attached materials (37.6%, 80/213), wear on metal parts (41.3%, 88/213), rust (23.9%, 51/213), and black spots (35.7%, 76/213). Among scratches, those in Teflon from 0-10 cm at the apex of the biopsy channel outlet and in metal from 0-5 cm at the biopsy channel inlet accounted for 58.4% (114/195) and 96.4% (188/195), respectively. CONCLUSIONS: Scratches were the most common form of damage in the endoscopic biopsy channels investigated and were related to the use of endoscopic accessories and cleaning brush materials. The incidence of other abnormalities gradually increased with the duration of use and began to increase significantly after 18 months. All abnormalities have a certain impact on the quality of endoscope reprocessing. We recommend that a borescope be used to check the inside of endoscopic biopsy channels regularly to determine the damage and cleaning conditions and that these channels be reprocessed, repaired, or replaced in a timely manner.

Tracking Spatial Distribution Alterations of Multiple Endogenous Molecules during Lentil Germination by MALDI Mass Spectrometry Imaging.

Exploring the spatial distribution alterations of metabolites during lentil germination is essential to reveal the nutritional value, physiological function, and metabolic pathway in lentils. Hence, an effective matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) method was established for the first time to visualize the spatial localization changes of 53 metabolites in lentils during germination for 12-72 h. The results of MALDI-MSI analysis showed that phosphatidylinositols, phosphatidylethanolamines, phosphatidylglycerols, and phosphatidic acids were mainly located in the cotyledons of lentils throughout the germination process, while triacylglycerols, phosphatidylcholines, diacylglycerols, amino acids, choline, and spermine spread throughout the lentil tissue at the initial stage of germination and gradually presented obvious distribution characteristics in the radicle with increasing germination time. Heat map analysis was used to visualize the correlations between lipid content changes and germination time, which supported the use of germinated lentils as nutraceutical or functional food.

Role of hydrogen sulphide in physiological and pathological angiogenesis.

The role of hydrogen sulphide (H2 S) in angiogenesis has been widely demonstrated. Vascular endothelial growth factor (VEGF) plays an important role in H2 S-induced angiogenesis. H2 S promotes angiogenesis by upregulating VEGF via pro-angiogenic signal transduction. The involved signalling pathways include the mitogen-activated protein kinase pathway, phosphoinositide-3 kinase pathway, nitric oxide (NO) synthase/NO pathway, signal transducer and activator of transcription 3 (STAT3) pathway, and adenosine triphosphate (ATP)-sensitive potassium (KATP ) channels. H2 S has been shown to contribute to tumour angiogenesis, diabetic wound healing, angiogenesis in cardiac and cerebral ischaemic tissues, and physiological angiogenesis during the menstrual cycle and pregnancy. Furthermore, H2 S can exert an anti-angiogenic effect by inactivating Wnt/ß-catenin signalling or blocking the STAT3 pathway in tumours. Therefore, H2 S plays a double-edged sword role in the process of angiogenesis. The regulation of H2 S production is a promising therapeutic approach for angiogenesis-associated diseases. Novel H2 S donors and/or inhibitors can be developed in the treatment of angiogenesis-dependent diseases.

A reliable and effective sample preparation protocol of MALDI-TOF-MSI for lipids imaging analysis in hard and dry cereals.

A superior sectioning sample preparation protocol is the basic guarantee for maintaining data reliability in MALDI-TOF-MSI analysis. Despite significant advances in sample preparation, visualization of lipids in hard and dry cereals remains difficult due to their inherent physicochemical properties. Thus, a cryosections preparation method was designed via poly-l-lysine soaking, conductive tape adhesion and embedding medium fixation, which preserved the spatial integrity of lipids in cereals without causing analyte delocalization and obvious background interference. Higher signal intensity and clearer imaging of lipids in rice, wheat and barley (Qingke) were obtained using the established sample preparation method. Moreover, the spatial distribution of lipids was visualized in rice with different storage years, which found that the phosphatidylinositols (PIs) and phosphatidylglycerols (PGs) could be used for evaluation of rice aging degree. Our study provided molecular level guidance for further discussion of rice aging mechanism, rice quality evaluation and safety monitoring.

The Role of Hydrogen Sulfide in the Development and Progression of Lung Cancer.

Lung cancer is one of the 10 most common cancers in the world, which seriously affects the normal life and health of patients. According to the investigation report, the 3-year survival rate of patients with lung cancer is less than 20%. Heredity, the environment, and long-term smoking or secondhand smoke greatly promote the development and progress of the disease. The mechanisms of action of the occurrence and development of lung cancer have not been fully clarified. As a new type of gas signal molecule, hydrogen sulfide (H2S) has received great attention for its physiological and pathological roles in mammalian cells. It has been found that H2S is widely involved in the regulation of the respiratory system and digestive system, and plays an important role in the occurrence and development of lung cancer. H2S has the characteristics of dissolving in water and passing through the cell membrane, and is widely expressed in body tissues, which determines the possibility of its participation in the occurrence of lung cancer. Both endogenous and exogenous H2S may be involved in the inhibition of lung cancer cells by regulating mitochondrial energy metabolism, mitochondrial DNA integrity, and phosphoinositide 3-kinase/protein kinase B co-pathway hypoxia-inducible factor-1α (HIF-1α). This article reviews and discusses the molecular mechanism of H2S in the development of lung cancer, and provides novel insights for the prevention and targeted therapy of lung cancer.

Cystathionine ß-Synthase Regulates the Proliferation, Migration, and Invasion of Thyroid Carcinoma Cells.

Thyroid cancer is considered to be one of the most common endocrine tumors worldwide. Cystathionine ß-synthase (CBS) plays a crucial role in the occurrence of several types of malignancies. And yet, the mechanism of action of CBS in the growth of thyroid carcinoma cells is still unrevealed. We found that CBS level in thyroid carcinoma tissue was higher than that in adjacent normal tissue. The overexpression of CBS enhanced the proliferation, migration, and invasion of thyroid cancer cells, while the downregulation of CBS exerted reverse effects. CBS overexpression reduced the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase in thyroid cancer cells, whereas CBS knockdown showed reverse trends. CBS overexpression decreased reactive oxygen species (ROS) levels but increased the levels of Wnt3a and phosphorylations of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR), ß-catenin, and glycogen synthase kinase-3 beta, while CBS knockdown exerted opposite effects. In addition, CBS overexpression promoted the growth of xenografted thyroid carcinoma, whereas CBS knockdown decreased the tumor growth by modulating angiogenesis, cell cycle, and apoptosis. Furthermore, aminooxyacetic acid (an inhibitor of CBS) dose-dependently inhibited thyroid carcinoma cell growth. CBS can regulate the proliferation, migration, and invasion of human thyroid cancer cells via ROS-mediated PI3K/AKT/mTOR and Wnt/ß-catenin pathways. CBS can be a potential biomarker for diagnosing or prognosing thyroid carcinoma. Novel donors that inhibit the expression of CBS can be developed in the treatment of thyroid carcinoma.

Analysis of the Influence of Thyroid Nodule Characteristics on the Results of Shear Wave Elastography.

Objective: To analyze the ultrasonic characteristics of false-negative and false-positive results of shear wave elastography (SWE) in the diagnosis of thyroid nodules to clarify the influence of nodular characteristics on SWE and to guide the clinical application of SWE. Methods: A total of 435 thyroid nodules from 343 patients with the diagnosis confirmed by surgical pathology were analyzed. Preoperative ultrasonography and SWE were conducted. The conventional ultrasound characteristics of thyroid nodules and the maximum Young's modulus were recorded. The false negativity and false positivity of SWE for the diagnosis of thyroid nodules were calculated. The ultrasonic characteristics of thyroid nodules with SWE false results were analyzed, and logistic regression analysis was adopted to determine the ultrasonic characteristics associated with SWE false results of thyroid nodules. Results: Among 323 malignant nodules, the SWE false negativity was 27.2% (88/323). The false positivity of SWE in 112 benign nodules was 19.6% (22/112). Regression analysis showed that an increase in the nodule volume increased the risk of SWE false-positive results (odds ratio [OR] 3.286; 95% confidence interval [CI]: 1.572-6.871; P = 0.002) and decreased the risk of false-negative results (OR 0.238; 95% CI: 0.115-0.493; P < 0.001). Nodules with coarse calcification had an increased risk of SWE false-positive results compared with those without calcification (OR 5.303; 95% CI: 1.098-25.619; P = 0.038). However, nodules with scattered hyperechoic foci had a reduced risk of SWE false-negative results (OR 0.515; 95% CI: 0.280-0.951; P = 0.034). Conclusion: Nodular size and calcification were correlated with SWE false results, and the clinical application of SWE should be combined with conventional ultrasound features. Fine needle aspiration or a puncture biopsy should be conducted if necessary.