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 that release H2S 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.

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.

[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.

High-throughput tandem-microwell assay for ammonia repositions FDA-Approved drugs to inhibit Helicobacter pylori urease.

To date, little attempt has been made to develop new treatments for Helicobacter pylori (H. pylori), although the community is aware of the shortage of treatments for H. pylori. In this study, we developed a 192-tandem-microwell-based high-throughput assay for ammonia that is a known virulence factor of H. pylori and a product of urease. We could identify few drugs, that is, panobinostat, dacinostat, ebselen, captan, and disulfiram, to potently inhibit the activity of ureases from bacterial or plant species. These inhibitors suppress the activity of urease via substrate-competitive or covalent-allosteric mechanism, but all except captan prevent the antibiotic-resistant H. pylori strain from killing human gastric cells, with a more pronounced effect than acetohydroxamic acid, a well-known urease inhibitor and clinically used drug for the treatment of bacterial infection. This study offers several bases for the development of new treatments for urease-containing pathogens and to study the mechanism responsible for the regulation of urease activity.

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.

Exploring lipid biomarkers of coronary heart disease for elucidating the biological effects of gelanxinning capsule by lipidomics method based on LC-MS.

High-throughput lipidomics technology was used to explore the potential therapeutic targets and mechanism of action of gelanxinning capsule on rat model with coronary heart disease (CHD). This study attempts to provide a novel method to interpret the molecular mechanism of traditional medicine. The lipid markers of CHD were determined by full-scan analysis based on ultra-performance liquid chromatography-high-definition mass spectrometry. Then, the metabolic changes associated with gelanxinning capsule treatment via the modulation of lipid biomarkers and pathway in rats were characterized. After gelanxinning treatment, the metabolic profile tended to recover compared with the model group. A total of 26 potential biomarkers were identified to represent the disorders of lipid metabolism in CHD animal model, of which 19 were regulated by gelanxinning capsule administration, and four metabolic pathways such as glycerophospholipid metabolism, sphingolipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, and glycerolipid metabolism were involved. From the pathway analysis, it was found that glycerophospholipid metabolism and sphingolipid metabolism with significant differences have the potential to be regarded as new targets for the treatment of CHD. Gelanxinning capsule with its good therapeutic effect protects against CHD by regulating lipid biomarkers and pathway from lipidomics-guided biochemical analysis.

The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases.

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

Photoluminescence quenching of inorganic cesium lead halides perovskite quantum dots (CsPbX3) by electron/hole acceptor.

Recently, all-inorganic cesium lead halide perovskites (CsPbX3) quantum dots (QDs) have attracted great attention due to their halogen composition and size tunable band gap engineering, the same physical mechanism that is responsible for excellent performance in light-emitting devices. However, little is known about the time-resolved fluorescence quenching dynamics process of these CsPbX3 QDs. In this article, we present comprehensive contrastive spectral studies on the electron and hole extraction dynamics of CsPbX3 colloidal QDs with and without quencher by time-resolved femtosecond transient absorption (TA) and time-correlated single-photon counting (TCSPC) spectroscopy methods. We have identified that the partial electrons of the conduction band and holes of the valence band of CsPbX3 QDs can be directly extracted by tetracyanoethylene (TCNE) and phenothiazine (PTZ), respectively. Moreover, compared with the CsPbBr3 QDs, the CsPbI3 QDs showed relatively slower charge extraction rates. We also found that the CsPbBr3 QDs with smaller size showed faster carrier recombination rates and photoluminescence (PL) decay lifetime due to the relatively stronger quantum confinement effects. We believe that this study may be useful for realising optimal applications in photovoltaic and light emission devices.

Size-dependent one-photon- and two-photon-pumped amplified spontaneous emission from organometal halide CH3NH3PbBr3 perovskite cubic microcrystals.

In the past few years, organometal halide light-emitting perovskite thin films and colloidal nanocrystals (NCs) have attracted significant research interest in the field of highly purified illuminating applications. However, knowledge of photoluminescence (PL) characteristics, such as amplified spontaneous emission (ASE) of larger-sized perovskite crystals, is still relatively scarce. Here, we presented room-temperature size-dependent spontaneous emission (SE) and ASE of the organometal halide CH3NH3PbBr3 perovskite cubic microcrystals pumped through one-photon-(1P) and two-photon-(2P) excitation paradigms. The results showed that the optical properties of SE and ASE were sensitively dependent on the sizes of perovskite microcrystals irrespective of whether 1P or 2P excitation was used. Moreover, by comparing the spectral results of 1P- and 2P-pumped experiments, 2P pumping was found to be an effective paradigm to reduce thresholds by one order of magnitude. Finally, we carried out fluences-dependent time-resolved fluorescence dynamics experiments to study the underlying effects of these scale-dependent SE and ASE. We found that the photoluminescence (PL) recombination rates sensitively became faster with increasing carriers' densities, and that the ASE pumped from larger-sized CH3NH3PbBr3 perovskite cubic microcrystals showed faster lifetimes. This work shows that micro-sized perovskite cubic crystals could be the ideal patterns of perovskite materials for realizing ASE applications in the future.

Downregulation and subcellular distribution of HER2 involved in MDA-MB-453 breast cancer cell apoptosis induced by lapatinib/celastrol combination.

PURPOSE: To investigate the effect and related molecular mechanisms of lapatinib/celastrol combination or single-agent treatment in HER2/neu-overexpressing MDA-MB-453 breast cancer cells. METHODS: The effects of treatment with lapatinib, celastrol or their combination on cell growth were determined using MTT assay. Drug synergy was determined using the combination index (CI) methods derived from Chou-Talalay equations using CalcuSyn software. Apoptotic morphology was observed by fluorescence microscope with Hoechst 33258 staining. Changes of apoptotic and growth pathways-related proteins were analysed by Western blot. The expression of HER2 of cell surface was performed by flow cytometry. Subcellular distribution of HER2 was observed by immunofluorescence study. RESULTS: Combination celastrol and lapatinib produced strong synergy in growth inhibition and apoptosis in comparison to single-agent treatment in HER2/neu-overexpressing MDA-MB-453 cells. Interestingly, compared with celastrol treatment alone, lapatinib/celastrol combination induced more HER2 membrane protein downregulation and ectopic to cytoplasm and nucleus in MDA-MB-453 cells. CONCLUSION: The combination of celastrol and lapatinib could be used as a novel combination regimen which provides a strong anticancer synergy in the treatment of HER2/neu-overexpressing cancer cells.

[Ecological suitability assessment for Notopterygium plants transplanting along altitudinal gradients].

A comprehensive field research had been focused on growing status, underground biomass and active constituents of Notopterygium incisum and N. franchetii to evaluate the ecological suitability and appropriate cultivation zones by growing the two species seedlings along different elevation gradient. The results showed that compared to the survival rate and underground biomass, the beneficial altitude region to N. incisum was ranged from 2 600 m to 4 100 m, while N. franchetii required a lower altitude which ranges from 1 700 m to 3 600 m. For the active constituent contents, the values were higher in the range of 2 600 to 3 600 m for N. incisum, but for N. franchetii, the range was form 1 700 to 3 600 m. This result provides instructional guidance and scientific basis for artificial cultivation of N. incisum and N. franchetii.

Berberine inhibits fluphenazine-induced up-regulation of CDR1 in Candida albicans.

Over-expression of the Candida drug resistance gene CDR1 is a common mechanism generating azole-resistant Candida albicans in clinical isolates. CDR1 is transcriptionally activated through the binding of the transcription factor Tac1p to the cis-acting drug-responsive element (DRE) in its promoter. We previously demonstrated that the combination of fluconazole (FLC) and berberine (BBR) produced significant synergy when used against FLC-resistant C. albicans in vitro. In this study, we found that BBR inhibited both the up-regulation of CDR1 mRNA and the transport function of Cdr1p induced by fluphenazine (FNZ). Further, electrophoretic mobility shift assays suggested that the transcription activation complex of protein-DRE was disrupted by BBR, and electrospray ionization mass spectrometry analysis showed that BBR bound to the DRE of CDR1. Thus we propose that BBR inhibits the FNZ-induced transcriptional activation of CDR1 in C. albicans by blocking transcription factor binding to the DRE of CDR1. These results contribute to our understanding of the mechanism of synergistic effect of BBR and FLC.

Epidemiological characteristics of acute disseminated encephalomyelitis in Nanchang, China: a retrospective study.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an autoimmune disease that typically follows a monophasic course and may affect any age group. The precise population-based incidence of ADEM is still unknown in most countries. In China, there is no ADEM surveillance system. The exact incidence of ADEM is difficult to estimate, and other epidemiological characteristics of ADEM are unknown. The purpose of this study is to investigate the epidemiological characteristics of ADEM in Nanchang, China. METHODS: A retrospective investigation was conducted with ADEM patients admitted to second-level and third-level hospitals in Nanchang from 2008 to 2010, aiming to analyse the epidemiologic characteristics of ADEM in the population in Nanchang. ADEM patients, defined as patients who were diagnosed according to the consensus definition of ADEM provided by the International Pediatric MS Study Group, were enrolled in the study. The data were extracted from the ADEM patients' medical records. RESULTS: Forty-seven ADEM patients were investigated. The average annual incidence was 0.31/100,000; the incidence among males (0.31/100,000) was nearly equal to that among females (0.31/100,000). The median age of onset was 25.97 years old, and the peak incidence was observed in the 5- to 9-year-old age group (0.75/100,000), followed by the over-60 age group (0.55/100,000). ADEM occurs throughout the year, but it occurs most frequently in March (n = 7) and least frequently in April and July (both n = 2). The patient numbers are roughly even in the other months. In the 2 months before the onset of ADEM, 15 patients presented with a preceding infection, but none of the patients received a vaccination. An increased number of vaccination was not accompanied by a corresponding increased number of cases of ADEM. CONCLUSIONS: The average annual incidence of ADEM was 0.31/100,000 in Nanchang. The incidence among males was nearly equal to that among females. The peak age of onset was 5-9 years old. The peak season of onset was not apparent. There was no evidence of an association between increased number of vaccines administered and number of cases of ADEM in Nanchang, China.

Celastrol enhanced the anticancer effect of lapatinib in human hepatocellular carcinoma cells in vitro.

PURPOSE: To investigate whether celastrol could show synergism combined with lapatinib in HepG2 human hepatocellular carcinoma (HCC) cell line in vitro. METHODS: The effects of treatment with lapatinib and/or celastrol on cell growth were determined using MTT assay. Drug synergy was determined using combination index (CI) methods derived from Chou-Talalay equations using CalcuSyn software. Apoptotic morphology was observed by fluorescence microscope with Hoechst 33258 staining. The expression of EGFR of cell surface was performed by flow cytometry. Changes of apoptotic and growth pathways-related proteins were analysed by Western blotting. RESULTS: The combination of celastrol and lapatinib produced strong synergy in growth inhibition and apoptosis in vitro in comparison to single-agent treatments. Moreover, celastrol enhanced the ability of lapatinib to down regulate EGFR protein expression in HepG2 cells. CONCLUSION: These data indicate that the combination of celastrol and lapatinib could be used as a novel combination regimen which could hopefully provide strong anticancer synergy in the treatment of HCC.

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.

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.

Dietary cholesterol alters memory and synaptic structural plasticity in young rat brain.

Cholesterol plays an important role in synaptic plasticity, learning and memory. To better explore how dietary cholesterol contributes to learning and memory and the related changes in synaptic structural plasticity, rats were categorized into a regular diet (RD) group and a cholesterol-enriched diet (CD) group, and were fed with respective diet for 2 months. Dietary cholesterol impacts on learning and memory, hippocampal synaptic ultrastructure, expression levels of postsynaptic density-95 (PSD-95), synaptophysin (SYP) and cannabinoid receptor type 1 (CB1R) were investigated. We found CD rats had better performances in learning and memory using Morris water maze and object recognition test than RD rats. The memory improvement was accompanied with alterations of synaptic ultrastructure in the CA1 area of the hippocampus evaluated by electron microscopy, enhanced immunoreactivity of SYP, a presynaptic marker in hippocampus detected by immunocytochemistry, as well as increased levels of PSD-95, SYP and decreased level of CB1R in brains of CD rats determined by Western blot. Taken together, the results suggest that the improvement of learning and memory abilities of the young adult rats induced by dietary cholesterol may be linked with changes in synaptic structural plasticity in the brain.

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.

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.