Insight into modulators of sphingosine-1-phosphate receptor and implications for cardiovascular therapeutics.

Cardiovascular disease is the leading cause of death worldwide, and it's of great importance to understand its underlying mechanisms and find new treatments. Sphingosine 1-phosphate (S1P) is an active lipid that exerts its effects through S1P receptors on the cell surface or intracellular signal, and regulates many cellular processes such as cell growth, cell proliferation, cell migration, cell survival, and so on. S1PR modulators are a class of modulators that can interact with S1PR subtypes to activate receptors or block their activity, exerting either agonist or functional antagonist effects. Many studies have shown that S1P plays a protective role in the cardiovascular system and regulates cardiac physiological functions mainly through interaction with cell surface S1P receptors (S1PRs). Therefore, S1PR modulators may play a therapeutic role in cardiovascular diseases. Here, we review five S1PRs and their functions and the progress of S1PR modulators. In addition, we focus on the effects of S1PR modulators on atherosclerosis, myocardial infarction, myocardial ischaemia/reperfusion injury, diabetic cardiovascular diseases, and myocarditis, which may provide valuable insights into potential therapeutic strategies for cardiovascular disease.

Targeted Mitochondrial Drugs for Treatment of Ischemia-Reperfusion Injury.

Ischemia-reperfusion injury is a complex hemodynamic pathology that is a leading cause of death worldwide and occurs in many body organs. Numerous studies have shown that mitochondria play an important role in the occurrence mechanism of ischemia-reperfusion injury and that mitochondrial structural abnormalities and dysfunction lead to the disruption of the homeostasis of the whole mitochondria. At this time, mitochondria are not just sub-organelles to produce ATP but also important targets for regulating ischemia-reperfusion injury; therefore, drugs targeting mitochondria can serve as a new strategy to treat ischemia-reperfusion injury. Based on this view, in this review, we discuss potential therapeutic agents for both mitochondrial structural abnormalities and mitochondrial dysfunction, highlighting the application and prospects of targeted mitochondrial drugs in the treatment of ischemia-reperfusion injury, and try to provide new ideas for the clinical treatment of the ischemia-reperfusion injury.

Targeted mitochondrial drugs for treatment of myocardial ischaemia-reperfusion injury.

Myocardial ischaemia-reperfusion injury (MI/RI) refers to the further damage done to ischaemic cardiomyocytes when restoring blood flow. A large body of evidence shows that MI/RI is closely associated with excessive production of mitochondrial reactive oxygen species, mitochondrial calcium overload, disordered mitochondrial energy metabolism, mitophagy, mitochondrial fission, and mitochondrial fusion. According to the way it affects mitochondria, it can be divided into mitochondrial quality abnormalities and mitochondrial quantity abnormalities. Abnormal mitochondrial quality refers to the dysfunction caused by the severe destruction of mitochondria, which then affects the balance of mitochondrial density and number, causing an abnormal mitochondrial quantity. In the past, most of the reports were limited to the study of the mechanism of myocardial ischaemia-reperfusion injury, some of which involved mitochondria, but no specific countermeasures were proposed. In this review, we outline the mechanisms for treating myocardial ischaemia-reperfusion injury from the direction of mitochondria and focus on targeted interventions and drugs to restore mitochondrial health during abnormal mitochondrial quality control and abnormal mitochondrial quantity control. This is an update in the field of myocardial ischaemia-reperfusion injury.

Therapeutic Strategies Targeting Mitochondrial Dysfunction in Sepsis-induced Cardiomyopathy.

Sepsis is an increasingly worldwide problem; it is currently regarded as a complex life-threatening dysfunction of one or more organs as a result of dysregulated host immune response to infections. The heart is one of the most affected organs, as roughly 10% to 70% of sepsis cases are estimated to turn into sepsis-induced cardiomyopathy (SIC). SIC can be defined as a reversible myocardial dysfunction characterized by dilated ventricles, impaired contractility, and decreased ejection fraction. Mitochondria play a critical role in the normal functioning of cardiac tissues as the heart is highly dependent on its production of adenosine triphosphate (ATP), its damage during SIC includes morphology impairment, mitophagy, biogenesis disequilibrium, electron transport chain disturbance, molecular damage from the actions of pro-inflammatory cytokines and many other different impairments that are major contributing factors to the severity of SIC. Although mitochondria-targeted therapies usage is still inadequate in clinical settings, the preclinical study outcomes promise that the implementation of these therapies may effectively treat SIC. This review summarizes the different therapeutic strategies targeting mitochondria structure, quality, and quantity abnormalities for the treatment of SIC.

Treatment of hypopharyngeal carcinoma complicated with diabetic nephropathy: a case report and literature review.

For elderly cancer patients with diabetic nephropathy, severe renal insufficiency leads to a very high risk of chemotherapy. Physicians and pharmacists must consider both the benefits of cancer treatment and the impact of antineoplastic drugs on patients' residual renal function, and choose appropriate chemotherapy regimens to balance the efficacy and safety of drugs. We report a case of a patient who presented with dysphagia and sore throat with serum creatinine of 169 µmol/L and fasting blood glucose of 7.9 mmol/L on admission. The main diagnosis was hypopharyngeal carcinoma with diabetic nephropathy. The clinical pharmacist reviewed the literature and analyzed the pharmacological and pharmacokinetic characteristics of anti-tumor drugs in patients, and adjusted the chemotherapy regimen and dose according to the renal function of patients. To the best of our knowledge, this is the first reported case of hypopharyngeal carcinoma with severe renal insufficiency treated successfully with multimodality therapy in China. The purpose of this case is to optimize the anti-tumor treatment regimen and drug dose adjustment of hypopharyngeal carcinoma with severe renal insufficiency, so as to provide a reference for clinicians and clinical pharmacists to use drugs rationally.

Individualized Treatment Analysis Of Breast Cancer With Chronic Renal Failure.

We report the case of a breast cancer patient with chronic renal failure (CRF). The clinical pharmacist adjusted the chemotherapy regimen and dosage according to the patient's renal function after reviewing the literature and analyzing the pharmacological and pharmacokinetic characteristics of the patient's antineoplastic drugs. To the best of our knowledge, this is the first report of successful multimodal treatment of breast cancer in a patient with CRF in China. The purpose of this case report is to optimize breast cancer therapy in patients with CRF and provide a reference for clinicians and clinical pharmacists to use antineoplastic drugs rationally.

Role of miR-511 in the Regulation of OATP1B1 Expression by Free Fatty Acid.

MicroRNAs (miRNAs) are a family of non-coding RNA that are able to adjust the expression of many proteins, including ATP-binding cassette transporter and organic cation transporter. We sought to evaluate the effect of miR-511 on the regulation of OATP1B1 expression by free fatty acids. When using free fatty acids to stimulate Chang liver cells, we found that the expression of miR-511 increased significantly while the expression of OATP1B1 decreased. We also proved that SLCO1B1 is the target gene of miR-511 with a bioinformatics analysis and using the dual luciferase reporter assay. Furthermore, the expressions of SLCO1B1 and OATP1B1 decreased if transfecting Chang liver cells with miR-511, but did not increase when transfecting the inhibitors of miR-511 into steatosis cells. Our study indicates that miR-511 may play an important role in the regulation of OATP1B1 expression by free fatty acids.

[Construction and application of a genechip method for detection of hepatitis B virus lamivudine-resistant mutants and basal core promotor/Pre-C mutants].

OBJECTIVE: The objective of this research is to construct a clinic-usable genechip method for detection of hepatitis B virus lamivudine-resistant mutants and basal core promotor/Pre-C mutants, compare this method with DNA sequencing to investigate this genechip's character (sensity, specificity, stability and practicability in clinic) and apply it in clinic. METHODS: This genechip detection method can detect the DNA and 8 mutative site of HBV, include 3 lamivudine-resistant mutation site(No. 180, 204, 207 site in DNA polymerase gene), 5 HBeAg escape-related mutation site (nt 1896, 1899, 1862, 1764,1762 site in BCP/Pre-C region).The results of genechip method was verified by DNA sequencing. RESULTS: In detecting HBV DNA, the results of genechip were agree with 100% of the results of DNA sequencing. In detecting HBV mutants, 251 sites (in 32 samples, 256 sites) showed the same results using both methods, and only 5 sites were not completely match (P > 0.05). In these 5 sites, genechip methods got multi-infection results, but sequencing got single-infection results. CONCLUSION: These results suggest that genechip method has the same positive rate and almost these same specificity with DNA sequencing method, and is better than DNA sequencing method in detecting multi-infected HBV strains. [Key words]

[Spatial-temporal dynamic change of land resource degradation in China].

Large scale spatial and temporal land use survey data were used to study the dynamics of land use change in China recently. With the aid of GIS, the spatial-temporal dynamic change of land resource degradation at the national level was investigated using authoritative datasets from detailed land use surveys (early 1990s approximately 2003). As a result, seven major types of land degradation processes were identified, including sandy desertification, rocky desertification, secondary salinification, non-agricultural land occupation, deforestation, natural grassland degradation and wetlands shrinking. This paper comprehensively explored the characteristics of these land degradation processes and revealed the status and trend of the holistic land resource degradation in China. Results shows that: (1) Although land degradation has been controlled in local area, but it is still continuing to spread in the whole country. The total degradation index of the holistic land resource presented fluctuating trend. Indexes of non-agricultural construction occupation and wetland shrinking process are far more than that of other process, which are two primary causes contribution to heading straight towards full-scale land resource deterioration in China. (2) Land resource degradation process of China focused on natural grass land, and non-agricultural construction land, which attained 66.27%; Land resource degradation rehabilitation mainly focused on desertification and forest restoration, which accounts for 57.5%. (3) Sandy desertification and rocky desertification process have been reversing greatly. The total net change of their quantities was decreased by 15,578km2. But most of the rehabilitation of land desertification was concentrated on the originally ecological vulnerable northwestern zone, whereas newly added desertified land has been expanding and aggravating in eastern zone, especially around river watersheds. (4) Over two-thirds of non-agriculture land expansion came from cultivated land. In addition, almost 60 percent of the loss cultivated land occupied by non-agricultural land was appeared in the Northeast, the Eastern coast and Central China where have many high productive agricultural lands of China. This kind of land degradation has threatened food security of China seriously. (5) However, large scale reclamation of ecological land transferred into cultivated land was the most dominant factor of degradation. For example, the conversion of wetland resource to croplands by reclamation accounts for over 50 percent of wetland shrinking.

[High-flux detection of HBV lamivudine resistant strains by genechip and analysis of mutant hotspots in those strains].

OBJECTIVE: Lamivudine resistant HBV strains in Shenzhen were detected at multiple sites and in large amounts to understand further the distribution of lamivudine resistant mutants. METHODS: 552 Hepatitis B patients's sera were examined using genechip method. Among them, 192 samples of lamivudine resistant mutant were further analyzed. RESULTS: In those 192 lamivudine resistant samples, 191 were YMDD mutants, 124 mutants of codon 528 and 9 mutants of codon 555. 88% YMDD mutants were multi-mutants of YVDD and codon 528; single mutants of YIDD; multi-mutants of YIDD and codon 528. 91% codon of YMDD mutants were GTG, ATT; the other 9% were ATA, ATC. CONCLUSIONS: These results suggest that mutants of codon 552 (YMDD) are core mutants. Mutants of codon 528 and 555 are incidental mutants, YVDD mutants always emerge with mutants of codon 528, but YIDD mutants appear differently. 9% YMDD mutants's codons are ATA or ATC. This may be the reason for the low positive rate shown by using the conventional PCR methods.

[Construction of a genechip method for detection of hepatitis B virus DNA, basal core promotor and Pre-C mutants].

BACKGROUND: To establish a genechip method for detection of hepatitis B virus (HBV) DNA, basal core promotor (BCP), and Pre-C mutants. METHODS: This study used two kinds of technology (PCR, oligochip), which can detect five mutant hotspots including nt 1 896, nt 1 899, nt 1 862, nt 1 764 and nt 1 762. The results of genechip method was verified by DNA sequencing. RESULTS: In detecting HBV DNA, the results of genechip were 100% consistent with those of DNA sequencing. In detecting HBV BCP and Pre-C mutants, 146 codons showed the same results using both methods, except for only 4 codons (P greater than 0.05). CONCLUSION: This convenient high throughput genechip method could detect several BCP and Pre-C mutant codons at the same time. These results suggest that genechip method has the same positive rate and specificity with DNA sequencing method. It has more advantages than the latter in detecting mixed mutants and therefore may be used in clinical practice.

[Study on purification technology of patchouly oil with molecular distillation].

OBJECTIVE: To establish an advanced purification techniques of the essential oils obtained from Pogostemon cablin. METHOD: Molecular distillation (MD) was applied. RESULT: Four distillates were obtained, chemical constituents of which were analyzed with GC-MS. Compared with those in original oils, the contents of active compounds (patchouli alcohol and pogostone) rose by 27%-47% in the distillates II and III. CONCLUSION: Molecular distillation (MD) effectively raises the contents of patchouli alcohol and pogostone. The work is of great economic and scientific significance for the industrialization of P. cablin and the discovery of new drugs.