Qi-Ju-Di-Huang-Pill delays the progression of diabetic retinopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Qi-Ju-Di-Huang-Pill (QJDH pill) is a Chinese decoction. Although it is commonly used to treat eye conditions, such as diabetic retinopathy (DR), its exact mechanism of action is unknown. AIM OF THE STUDY: To investigate the specific mechanism by which QJDH pill slows the progression of diabetic retinopathy (DR) based on animal and cellular experiments. MATERIAL AND METHODS: The major components of QJDH pill were characterized by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLCMS/MS). C57BL/6J mice were randomly divided into five groups as follows: normal group (control group), model group (STZ group), low-dosage QJDH pill group (QJDH-L group), medium-dosage QJDH pill group (QJDH-M group) and high-dosage QJDH pill group (QJDH-H group). Changes in water intake, urination, food intake, and body mass were monitored weekly, while changes in blood glucose were monitored monthly. Fluorescein fundus angiography (FFA), optical coherence tomography angiography (OCTA), and optical coherence tomography (OCT) were utilized to analyze the changes in fundus imaging indications. Hematoxylin & eosin (H&E) and transmission electron microscopy (TEM) were employed to examine histopathologic and ultrastructural changes in retina. The levels of interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) in peripheral blood were detected using Enzyme-linked immunosorbent assay (ELISA). The mouse retina apoptotic cells were labeled with green fluorescence via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (Tunel). The protein levels of Bcl-2-Associated X (Bax), B cell lymphoma 2 (Bcl-2), Caspase-3, PI3K, phosphorylated PI3K (p-PI3K), protein kinase B (AKT) and phosphorylated AKT (p-AKT) were quantified by Western blot (WB). The retinal pigment epithelium (RPE) cells were cultured and classified into five groups as follows: normal glucose group (NG group), high glucose group (HG group), high glucose + QJDH pill group (HG + QJDH group), high glucose + inhibitor group (HG + LY294002 group), and high glucose + inhibitor + QJDH pill group (HG + LY294002 + QJDH group). Cell viability and apoptosis were detected via Cell Counting Kit-8 (CCK8) and then analyzed by flow cytometry. RESULTS: In vivo experiments revealed that the QJDH pill effectively reduced blood glucose, symptoms of increased water intake, elevated urination, increased food intake and decreased body mass in DR mice. QJDH pill also slowed the development of a series of fundus imaging signs, such as retinal microangiomas, tortuous dilatation of blood vessels, decreased vascular density, and thinning of retinal thickness, downregulated IL-6, IL-17, TNF-α, and VEGF levels in peripheral blood, and inhibited retinal cell apoptosis by activating the PI3K/AKT signaling pathway. Moreover, in vitro experiments showed that high glucose environment inhibited RPE cell viability and activated RPE cell apoptosis pathway. In contrast, lyophilized powder of QJDH pill increased RPE cell viability, protected RPE cells from high glucose-induced damage, and decreased apoptosis of RPE cells by activating the pi3k pathway. CONCLUSION: QJDH pill induces hypoglycemic, anti-inflammatory effects, anti-VEGF and anti-retinal cell apoptosis by activating PI3K/AKT signaling pathway, and thus can protect the retina and slow the DR progression.

Morusin Inhibits RANKL-induced Osteoclastogenesis and Ovariectomized Osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a classic type of osteoporosis that has gradually become a significant health problem worldwide. There is an urgent need for a safe alternative therapeutic agent considering the poor therapeutic strategies currently available for this disease. The roots and bark of the Morus australis tree (Moraceae) are used to make a traditional Chinese medicine known as "Morusin", and accumulating evidence has demonstrated its multiple activities, such as anti-inflammatory and anti-tumor effects. OBJECTIVE: In this study, we aim to explore the effect of Morusin on mouse osteoclasts and its mechanism. METHODS: In this study, we explored the inhibitory effects of Morusin on murine osteoclasts in vitro and its mechanism, and the protective effect of Morusin on an ovariectomy (OVX)-induced osteoporosis model in vivo. RESULTS: The results showed that Morusin prevented OVX-induced bone loss and dramatically decreased RANKL-induced osteoclastogenesis. Morusin interfered with RANKL-activated NF- κB, MAPK, and PI3K/AKT signaling pathways. The expression of three master factors that control osteoclast differentiation, c-Fos, NFATc1, and c-Jun, was reduced by Morusin treatment. Collectively, in vitro results indicated that Morusin has a protective effect on OVX-induced bone loss in a mouse model. CONCLUSION: Our data provide encouraging evidence that Morusin may be an effective treatment for PMOP.

High incidence of drug-resistant Mycobacterium tuberculosis in Hainan Island, China.

OBJECTIVES: To assess the proportion of drug-resistant tuberculosis (TB) cases and to identify independent risk factors associated with drug-resistant TB in Hainan. METHODS: Descriptive analysis of demographic and clinical data of culture-positive TB patients to assess the trends in drug-resistant TB at the Provincial Clinical Center on Tuberculosis of Hainan between 2014 and 2017. RESULTS: 994 patients were recruited into the study. Overall, the proportion of patients resistant to at least one TB drug tested was 36.1% (359/994). The most frequent resistance was to isoniazid (INH, 29.8%), followed by rifampin (RIF, 29.3%), streptomycin (19.3%), ofloxacin (OFX, 17.4%), ethambutol (9.5%) and kanamycin (KAN, 3.2%). Of 291 RIF-resistant isolates, 228 (78.4%) were also resistant to INH, while the remaining 63 (21.6%) were susceptible to INH. Among those with multidrug-resistant tuberculosis (MDR-TB), 41.2% had additional resistance to OFX and 3.9% to KAN. 8.8% of MDR-TB patients were affected by extensively drug-resistant (XDR-TB). Females were more likely to infected with MDR-TB than males, and young people (<20 years old) were more likely to have MDR-TB; patients exhibited decreasing MDR-TB risk with increasing age. CONCLUSIONS: Our data provide the first primary understanding of the drug-resistant TB epidemic in Hainan. The high incidence of drug resistance, especially RIF and FQ resistance, highlight the importance of interventions for preventing epidemics of drug-resistant TB. Younger age is an independent predictor of MDR-TB, reflecting the potential transmission in this population.

OBJECTIFS: Evaluer la proportion de cas de tuberculose (TB) résistante aux médicaments et identifier les facteurs de risque indépendants associés à la TB résistante à Hainan. MÉTHODES: Analyse descriptive des données démographiques et cliniques de patients TB à culture positive pour évaluer les tendances de la TB résistante au Centre Clinique Provincial de la TB de Hainan entre 2014 et 2017. RÉSULTATS: 994 patients ont été recrutés dans l'étude. Au total, la proportion de patients résistant à au moins un antituberculeux testé était de 36,1% (359/994). La résistance la plus fréquente était à l'isoniazide (INH, 29,8%), suivi par la rifampine (RIF, 29,3%), la streptomycine (19,3%), l'ofloxacine (OFX, 17,4%), l'éthambutol (9,5%) et la kanamycine (KAN, 3,2%). Sur les 291 isolats résistants au RIF, 228 (78,4%) étaient également résistants à l'INH, tandis que les 63 restants (21,6%) étaient sensibles à l'INH. Parmi ceux avec la multirésistance (TB-MDR), 41,2% présentaient une résistance supplémentaire à l'OFX et 3,9% à la KAN. 8,8% des patients atteints de TB-MDR étaient atteints d'une TB ultrarésistante (TB-XDR). Les femmes étaient plus susceptibles d'être infectées par la TB-MDR que les hommes et les jeunes (<20 ans) étaient plus susceptibles d'être atteints de TB-MDR; les patients présentaient un risque décroissant de TB-MDR avec l'âge. CONCLUSIONS: Nos données fournissent la première compréhension importante de l'épidémie de TB résistante à Hainan. L'incidence élevée de la résistance aux médicaments, en particulier des résistances RIF et FQ, souligne l'importance des interventions pour prévenir les épidémies de TB résistante. L'âge plus jeune est un facteur indépendant de prédiction de la TB-MDR, reflétant le potentiel de transmission dans cette population.