Research progress on chemical constituents and pharmacological effects of Ajania plants / 中国中药杂志

Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.

Switching from efavirenz to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide reduces central nervous system symptoms in people living with HIV / 中华医学杂志(英文版)

BACKGROUND@#Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting.@*METHODS@#A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.@*RESULTS@#One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable.@*CONCLUSIONS@#The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.

Diagnosis of elephantiasis nostras verrucosa as a clinical mani-festation of Kaposi's sarcoma / Diagnóstico de elefantiasis nostras verrucosa como mani-festación clínica del Sarcoma de Kaposi

Elephantiasis nostras verrucosa, a rare manifestation of Kaposi's sarcoma, is a progressive cutaneous hypertrophy caused by chronic non-filarial lymphedema secondary to obstruction of the lymphatic system that can lead to severe disfigurement of parts of the body that have gravity-dependent blood flow, due to edema, fibrosis, and hyperkeratosis, especially lower extremities. Among the various conditions that can induce chronic lymphedema are tumors, trauma, radiotherapy, obesity, hypothyroidism, chronic venous stasis, and AIDS-related Kaposi's sarcoma. Kaposi's sarcoma is a vascular tumor associated with the presence of human gammaherpesvirus 8 that is predominantly cutaneous, locally aggressive, with metastasis, and is associated with the production of factors that favor inflammation, lymphatic obstruction, and lymphedema.

Alta prevalencia de hipovitaminosis D en personas infectadas con HIV atendidas en un centro ambulatorio de la ciudad de Buenos Aires / High prevalence of hypovitaminosis D in HIV-infected persons attending an outpatient clinic, Buenos Aires city

La hipovitaminosis D es frecuente en el mundo. Según estudios realizados entre 1987 y 2015, en Argentina la prevalencia fue > 40%. En personas con infección por HIV variaría entre 20 y 90%, pero en nuestro medio no se conoce con precisión. Nuestro objetivo fue determinar la prevalencia de hipovitaminosis D en una cohorte de adultos con infección por HIV asistidos en forma ambulatoria en la ciudad de Buenos Aires. Se analizaron retrospectivamente las historias clínicas de 814 sujetos mayores de 18 años HIV positivos con al menos una determinación de vitamina D. La mediana de edad fue 44 años (rango intercuartílico 21-80), 746 (91.6%) eran hombres y 813 (99.9%) recibían tratamiento antirretroviral. Se realizó análisis uni y multivariado para determinar asociación entre hipovitaminosis D y valores de CD4, carga viral para HIV y terapia antirretroviral. La prevalencia de hipovitaminosis D fue 79.7% (insuficiencia 34.2%, deficiencia 45.5%). No se encontró asociación con el uso de efavirenz o inhibidores de la proteasa (p = 0.86 en ambos casos), con el recuento de linfocitos CD4, ni con la carga viral plasmática (p = 0.81 y 0.74, respectivamente). El presente estudio muestra que, en nuestro medio, la hipovitaminosis D es muy frecuente en personas con infección por HIV. Aun cuando no revela evidencia de relación con carga viral para HIV, estado inmune, ni tratamiento antirretroviral, es necesaria la búsqueda sistemática de hipovitaminosis D en esta población, en vista de la alta frecuencia de osteopenia y osteoporosis y el mayor riesgo de fracturas descripto en personas HIV positivas.

Hypovitaminosis D is frequent worldwide. In Argentina, according to studies conducted between 1987 and 2015, prevalence was > 40% in the general population. In people living with HIV it may vary between 20 and 90%, but the prevalence in our environment is not known. Our objective was to determine the prevalence of hypovitaminosis D in a cohort of adults with HIV infection in the city of Buenos Aires. We analyzed retrospectively medical records of 814 HIV positive subjects older than 18 years with at least one determination of vitamin D. The median age was 44 years (interquartile range 21-80), 746 (91.6%) were men, and 813 (99.9%) were on antiretroviral treatment. Univariate and multivariate analyses were performed to determine the association of hypovitaminosis D with CD4 values, viral load for HIV, and antiretroviral therapy. The present study shows that, in our environment, hypovitaminosis D is very common in people with HIV infection. Although it does not reveal evidence of a relationship with viral load for HIV, immune status, or antiretroviral treatment, the systematic search for hypovitaminosis D is mandatory in this population, taking into account its high frequency and the increased risk of osteopenia, osteoporosis and fractures, as described in people with HIV.

Efectividad y seguridad del esquema genérico lamivudina/tenofovir y efavirenz en pacientes con VIH/SIDA naïve: estudio fase IV no aleatorizado, Cali-Colombia 2012-2014 / Effectiveness and safety of generic version of lamivudine/tenofovir and efavirenz in treatment naïve HIV-infected patients: a nonrandomized, open-label, phase IV study in Cali-Colombia, 2012-2014

Resumen Antecedentes: Los estudios clínicos orientados a evaluar la calidad de medicamentos genéricos pueden ser útiles para fortalecer políticas de acceso a terapia anti-retroviral combinada (TARc). Objetivo: Describir la efectividad y seguridad del esquema genérico lamivudina/tenofovir/efavirenz (3TC/TDF/EFV) en pacientes con infección por VIH/SIDA naïve, pertenecientes a un programa de atención integral. Materiales/Métodos: Estudio clínico prospectivo fase IV abierto y sin grupo control. Entre 2012-2014, se incluyeron y siguieron 40 pacientes con infección por VIH/SIDA naïve y con indicación para iniciar tratamiento. Los pacientes fueron tratados con el esquema genérico 3TC/TDF/EFV y fueron seguidos durante 12 meses. El seguimiento incluyó valoración clínica, parámetros inmunovirológicos y de laboratorio, al inicio del tratamiento y a los 3, 6 y 12 meses. Resultados: De los 40 pacientes, 30 (75%) cumplieron los doce meses de tratamiento; de ellos, 80% alcanzó CV indetectable (< 40 copias/mL) y 83,3% CV < 50 copias/mL. Adicionalmente, en el grupo hubo un incremento en la mediana de 173 linfocitos TCD4/mm3. Por su parte, los resultados del hemograma completo, creatininemia y transaminasas hepáticas se conservaron en rangos normales y no generaron cambios del TARc. Los efectos adversos reconocidos para estos medicamentos se presentaron en menos de 10% de los pacientes y no tuvieron implicaciones graves. Conclusiones: En este grupo pequeño de pacientes, el esquema genérico 3TC/TDF/EFV es efectivo y seguro en el tratamiento de pacientes con infección por VIH/SIDA naïve, y su perfil de efectividad y seguridad es similar al del esquema 3TC/TDF/EFV innovador en pacientes con condiciones clínicas similares.

Background: Clinical studies aimed to evaluating the quality of generic drugs may be useful to strengthen policies of access to combined antiretroviral therapy (cART). Aim: To describe the effectiveness and safety of the generic schema lamivudine/tenofovir/efavirenz (3TC/TDF/EFV) in patients with HIV/AIDS naive, belonging to a comprehensive care program. Methods: A nonrandomized, open-label, phase IV study, during 2012 to 2014 naive HIV-infected patients 18 years or older with indication to receive cART were recruited. Patients were treated with generic scheme 3TC/TDF/EFV and were followed-up during 12 months. Clinical, immunological and laboratory parameters were assessed at baseline, 3, 6 and 12 months of treatment. Results: Of the 40 patients, 30 (75%) met the 12 months of treatment; of them, 80% achieved undetectable viral load (< 40 copies/mL) and 83.3% viral load < 50 copies/mL. Additionally, there was a significant increase (173 cells/mm3) in the median for CD4 T lymphocyte count. Moreover, the results of the whole blood count, creatinine and transaminases were preserved in normal ranges and did not generate changes in the cART. Potential side effects of antiretroviral drugs occurred in less than 10% of patients and had no serious implications. Conclusions: In this small group of patients, the generic scheme 3TC/TDF/EFV is effective and safe in the treatment of patients with HIV/AIDS naïve, and its effectiveness and safety profile is similar to show by innovator scheme 3TC/TDF/EFV in patients with similar clinical conditions. Registro Estudio: Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000134. Registered 20 July 2012.

The Role of Hydrogen Sulfide in Acute Liver Injury Induced by Traumatic Stress in Rats / 法医学杂志

OBJECTIVE@#To explore the role of hydrogen sulfide (H2S) in acute liver injury induced by crushing hind limbs of rats.@*METHODS@#The rats were randomly divided into the following groups: control, crushing, H2S donor sodium hydrosulfide (NaHS) + crushing, H2S inhibitor propargylglycine (PAG) + crushing group. The acute liver injury model was established by 'crushing the hind limbs of rats with standard weight. Rats were sacrificed at 30 min and 120 min after the crush. The activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured by colorimetric method, and the content of H2S in plasma and the contents of malondialdehyde (MDA), protein carbonyl, glutathione (GSH) in the liver and the activity of H2S generating enzyme (cystathionine y-lyase, CSE) were determined by chemical method. The expression of CSE mRNA in liver was detected by RT-PCR.@*RESULTS@#For crush injury group, the levels of AST and ALT in serum, MDA and protein carbonyl in liver increased. The levels of GSH, CSE, CSE mRNA in liver and H2S in serum decreased. The administration of NaHS before limbs crush could attenuate the changes of liver injury, but the pre-treatment with PAG could exacerbate the changes.@*CONCLUSION@#The decrease of H2S production could involve in mediating the acute liver injury induced by traumatic stress in rats.

Phytochemical progress made in investigations of Angelica sinensis (Oliv.) Diels / 中国天然药物

The phytochemical progress on Angelica sinensis (Oliv.) Diels over the past decades is summarized. Since 1970s, 165 chemical constituents, including phthalides, phenylpropanoids, terpenoids and essential oils, aromatic compounds, alkaloids, alkynes, sterols, fatty acids, and polysaccharides have been isolated or detected from the various parts of the title plant.

Endogenous cystathionine-gamma-lyase/hydrogen sulfide pathway regulates apoptosis of HepG2 cells / 药学学报

This study is to investigate the role of endogenous CSE/H2S in regulating apoptosis of HepG2 cells. MTT and Trypan blue assay were performed to determine the effect of CSE inhibitor PAG and CSE siRNA on proliferation of HepG2. Production of H2S from HepG2 cells was assessed spectrophotometrically using N, N-dimethyl-p-phenylenediamine-dihydrochloride. Cells apoptosis was detected by means of double staining of Hoechst 33342 and PI with Array Scan V(TI)HCS600 High-Contents. Dihydroethidine (DHE) and 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay was used to determine intracellular superoxide anion and ROS level. Reduced glutathione (GSH) was determined by OxiSelect Total Glutathione Assay Kit. Recombinant plasmid pcDNA 3.1/myc-His(-)-CSE was constructed and transfected into 293T cells to rescue the ROS and GSH level to further investigate the effect of CSE/H2S on ROS and GSH. Western blotting was performed to test the effect of CSE siRNA on expression of activated caspase 3 and p-AKT and Nrf2 protein. The results showed that PAG and CSE siRNA could significantly decrease the production of H2S in HepG2 cells and inhibit the proliferation of HepG2 cells at a dose-dependent and time-dependent manner, respectively. PAG and CSE siRNA could promote the cell apoptosis of HepG2 cells. Moreover, PAG and CSE siRNA induced increased ROS generation and depletion of the critical antioxidant GSH and recombinant plasmid pcDNA 3.1/myc-His(-)-CSE rescued the level of ROS and GSH. Meanwhile, CSE siRNA increased the expression of activated caspase 3, but CSE siRNA did not affect the expression of p-AKT and Nrf2. These results suggested that the CSE/H2S pathway was involved in suppression of HepG2 cell growth and promoted apoptosis of HepG2 cells in an oxidative stress-dependent manner.

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg percent] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg percent], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

Hydrogen sulfide induces apoptosis of pulmonary artery smooth muscle cell in rats with pulmonary hypertension induced by high pulmonary blood flow / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Abnormal apoptosis of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in the pulmonary artery structural remodeling and pulmonary hypertension. We investigated possible effect of endogenous hydrogen sulfide (H2S) on apoptosis of PASMCs during the development of pulmonary hypertension induced by high pulmonary blood flow.</p><p><b>METHODS</b>Thirty-nine male Sprague-Dawley rats were randomly assigned to 4-week control, 4-week shunt, 4-week shunt + propargylglycine (PPG), 11-week control, 11-week shunt and 11-week shunt + sodium hydrosulfide (NaHS) groups. Rats in 4-week shunt, 4-week shunt + PPG, 11-week shunt and 11-week shunt + NaHS groups underwent an abdominal aorta-inferior vena cava shunt. Rats in 4-week shunt + PPG group were intraperitoneally injected with PPG, an inhibitor of endogenous H2S production, for 4 weeks. Rats in 11-week shunt + NaHS group were intraperitoneally injected with NaHS, a H2S donor, for 11 weeks. Lung tissue H2S was evaluated by sulfide-sensitive electrode. Apoptosis of PASMCs were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). Expressions of Fas, bcl-2 and caspase-3 in the PASMCs were analyzed with immunochemical staining.</p><p><b>RESULTS</b>Four weeks after the shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P < 0.01), but expression of bcl-2 increased significantly (P < 0.01). PPG administration further inhibited the apoptosis of PASMCs, downregulated the expression of Fas and caspase-3 (P < 0.01), but increased the expression of bcl-2 (P < 0.01). After 11 weeks of shunting operation, the apoptosis of PASMCs and expression of Fas and caspase-3 were significantly decreased (P < 0.01), but expression of bcl-2 increased obviously (P < 0.01). NaHS administration significantly increased the apoptosis of PASMCs, upregulated the expression of Fas and caspase-3, but inhibited the expression of bcl-2.</p><p><b>CONCLUSIONS</b>H2S induces the apoptosis of PASMCs in the development of high pulmonary blood flow-induced pulmonary hypertension by activating the Fas pathway and inhibiting the bcl-2 pathway.</p>

Hydrogen sulfide facilitates carotid sinus baroreceptor activity in anesthetized male rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been reported that hydrogen sulfide (H(2)S) could relax vascular smooth muscle by direct activation of K(ATP) channels and hyperpolarization of the membrane potential. Recently, our study has shown that H(2)S facilitated carotid baroreflex. This study was conducted to investigate the effect of H(2)S on carotid baroreceptor activity (CBA).</p><p><b>METHODS</b>The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus.</p><p><b>RESULTS</b>H(2)S (derived from NaHS) 25, 50 and 100 micromol/L facilitated CBA, which shifted FCCB to the left and upward. There was a marked increase in peak slope (PS) and peak integral value of carotid sinus nerve charge (PIV) in a concentration-dependent manner. Pretreatment with glibenclamide (20 micromol/L), a K(ATP) channel blocker, the above effects of H(2)S on CBA were abolished. Pretreatment with Bay K8644 (an agonist of calcium channels, 500 nmol/L) eliminated the role of H(2)S on CBA. An inhibitor of cystathionine gamma-lyase (CSE), DL-propargylglycine (PPG, 200 micromol/L) inhibited CBA in male rats and shifted FCCB to the right and downward.</p><p><b>CONCLUSIONS</b>Our results suggest that exogenous H(2)S exerts a facilitatory role on isolated CBA through opening K(ATP) channels and further closing the calcium channels in vascular smooth muscle. Endogenous H(2)S may activate CBA in vivo.</p>

Survival, nodulation and N2 fixation ability of root nodule bacteria under different nutritional regimes.

Eleven strains of Rhizobium and five strains of Bradyrhizobium were examined for their viability as well nodulation and nitrogen fixation ability after storage under different conditions for two years. The storage conditions comprised lateritic soil, lateritic soil plus 1% mannitol, lateritic soil plus 0.1% yeast extract, lateritic soil plus 1% mannitol and 0.1% yeast extract, organic soil, organic soil plus 1% mannitol, organic soil plus 0.1% yeast extract, organic soil plus 1% mannitol and 0.1% yeast extract, and sterile distilled water. All the slow growing strains showed better viability than the fast growing strains in any of these conditions. The survived strains maintained their nodulation ability about 50-60% after one year and 40-50% after two years of preservation as compared to control, but the nodulation ability in sterile distilled water was very poor. Acetylene reduction activity in the nodules was found to be 70-90% and 50-70% after 12 and 24 months of preservation, respectively. The strains retained their phenotypic characters like antibiotic resistance and salt tolerance up to their highest survivability in respective nutritional condition.

Effect of petroleum ether extract of Panax ginseng roots on proliferation and cell cycle progression of human renal cell carcinoma cells

Panax ginseng roots have long been used as a medicinal herb in oriental countries. We have investigated anti-proliferative effects of lipid soluble Panax ginseng components on human renal cancer cell lines. Petroleum ether extract of Panax ginseng roots (GX-PE) or its partially purified preparation (7:3 GX) was added to cultures of three human renal cell carcinoma (RCC) cell lines, A498, Caki-1, and CURC II. Proliferation of RCC cells was estimated by a [3H]thymidine incorporation assay and cell cycle distribution was analyzed by flow cytometry. GX-PE, 7:3 GX, panaxydol and panaxynol inhibited proliferation of all three RCC cell lines in a dose dependent manner in vitro with an order of potency, 7:3 GX > panaxydol > panaxynol = GX-PE. Additive effect of interleukin 4 was also demonstrated, most prominently in Caki-1 which responded poorly to GX-PE alone. Analysis of cell cycle in CURC II and Caki-1 treated with GX-PE demonstrated increase in G1 phase population and corresponding decrease in S phase population. The present study demonstrated that proliferation of human RCC cell lines were inhibited by lipid soluble components of Panax ginseng roots by blocking cell cycle progression at G1 to S phase transition.