Hypericum sampsonii exhibits anti-inflammatory activity in a lipopolysaccharide-induced sepsis mouse model.

Background and aim: Sepsis causes an uncontrolled systemic response characterized by excessive inflammation and immune suppression, leading to multiple organ failure and death. An effective therapeutic strategy for sepsis-related syndromes is urgently needed. Hypericum sampsonii Hance (HS) is a folk herbal plant used to treat arthritis and dermatitis, but the anti-inflammatory properties of HS and its related compounds have rarely been investigated. In this study, we aimed to explore the anti-inflammatory effects of HS. Experimental procedure: Models of bacterial lipopolysaccharide (LPS)-induced activated macrophages and endotoxemia mice were used, in which the TLR4/NF-κB signaling pathway is upregulated to trigger inflammatory responses. The HS extract (HSE) was delivered into LPS-induced endotoxemia mice via oral administration. Three compounds were purified using column chromatography and preparative thin layer chromatography and were validated by physical and spectroscopic data. Results: HSE suppressed NF-κB activation and proinflammatory molecules (TNF-α, IL-6, iNOS) in LPS-activated RAW 264.7 macrophages. Furthermore, oral administration of HSE (200 mg/kg) to LPS-treated mice improved the survival rate, restored body temperature, decreased TNF-α and IL-6 in serum, and reduced IL-6 expression in bronchoalveolar lavage fluid (BALF). In lung tissues, HSE reduced LPS-induced leukocyte infiltration and the expression of proinflammatory molecules (TNF-α, IL-6, iNOS, CCL4 and CCL5). Three pure compounds isolated from HSE, including 2,4,6-trihydroxybenzophenone-4-O-geranyl ether, 1-hydroxy-7 methoxyxanthone and euxanthone, were demonstrated to exhibit anti-inflammatory activities in LPS-stimulated RAW 264.7 macrophages. Conclusion: The present study demonstrated the anti-inflammatory effects of HS in vitro and in vivo. Further clinical studies of HS in human sepsis are warranted.

Hypothalamic Menin regulates systemic aging and cognitive decline.

Aging is a systemic process, which is a risk factor for impaired physiological functions, and finally death. The molecular mechanisms driving aging process and the associated cognitive decline are not fully understood. The hypothalamus acts as the arbiter that orchestrates systemic aging through neuroinflammatory signaling. Our recent findings revealed that Menin plays important roles in neuroinflammation and brain development. Here, we found that the hypothalamic Menin signaling diminished in aged mice, which correlates with systemic aging and cognitive deficits. Restoring Menin expression in ventromedial nucleus of hypothalamus (VMH) of aged mice extended lifespan, improved learning and memory, and ameliorated aging biomarkers, while inhibiting Menin in VMH of middle-aged mice induced premature aging and accelerated cognitive decline. We further found that Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism. Aging-associated Menin reduction led to impaired D-serine release by VMH-hippocampus neural circuit, while D-serine supplement rescued cognitive decline in aged mice. Collectively, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.

[Treatment of Knee Osteoarthritis with Acupuncture plus Intra-articular Injection of Sodium Hyaluronate].

OBJECTIVE: To examine the clinical benefits of acupuncture combined with intra-articular injection of sodium hyaluronate for knee osteoarthritis (KOA) patients. METHODS: A total of 150 KOA patients were randomized into simple medication and acupuncture plus medication (combined treatment) groups (n＝75 in each). For all the patients, intra-articular injection of sodium hyaluronate (2 mL) was performed once a week for 5 weeks, and for patients of the combined treatment group, filiform needles were separately inserted into unilateral or bilateral Zusanli (ST 36), Liangqiu (ST 34), Yanglingquan (GB 34), Yinlingquan (SP 9), Xiyangguan (GB 33), Dubi (ST 35), Neixiyan (EX-LE 4) and Xuehai (SP 10) according to the focus, and manipulated with the uniform reinforcing and reducing technique, followed by retaining the needles for 30 min. The acupuncture treatment was given once every day or every other day, 5 weeks in total. The visual analog scale (VAS) was used to assess the pain severity of knee-joint, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) employed to assess the 1) pain severity during various positions or movements (20 points), 2) severity of joint stiffness (8 points), and 3) difficulty in performing daily functional activities (68 points). The therapeutic effect was evaluated according to the decreased level of WOMAC subscale scores and improvement of daily activities. RESULTS: After the treatment, the VAS scores of both medication and combined treatment groups were decreased significantly in comparison with their own pre-treatment in each group (P<0.05), and that of the combined treatment group was significantly lower than that of the medication group (P<0.05). WOMAC and daily activity fin-dings showed that of the two 75 KOA patients in the medication and combined treatment groups, 16 (21.33%) and 32 (42.67%) experienced marked improvement, 46 (61.33%) and 38 (50.67%) were improved, and 13 (17.33%) and 5 (6.67%) ineffective, with the total effective rates being 82.67% and 93.33%, respectively. The therapeutic effect of the combined treatment group was apparently superior to that of the simple medication group (P<0.05). CONCLUSION: Acupuncture combined with intra-articular injection of sodium hyaluronate is effective in improving KOA patients' pain severity and other symptoms as well as functional activities.

Anticonvulsant and Sedative Effects of Eudesmin isolated from Acorus tatarinowii on mice and rats.

This paper was designed to investigate anticonvulsant and sedative effects of eudesmin isolated from Acorus tatarinowii. The eudesmin (5, 10, and 20 mg/kg) was administered intraperitoneally (i.p.). The maximal electroshock test (MES) and pentylenetertrazole (PTZ)-induced seizures in male mice were used to evaluate anticonvulsant activities of eudesmin, and sedative effects of eudesmin were evaluated by pentobarbital sodium-induced sleeping time (PST) and locomotor activity in mice. Finally, the mechanisms of eudesmin were investigated by determining contents of glutamic acid (Glu) and gamma-aminobutyric acid (GABA) in epileptic mice, and expressions of glutamate decarboxylase 65 (GAD65), GABAA , Bcl-2, and caspase-3 in the brain of chronic epileptic rats. Results of MES and PTZ tests revealed that eudesmin possesses significant anticonvulsant effects, and the PST and locomotor activity tests demonstrated that eudesmin has significant sedative effects. Furthermore, our study revealed that after treatment with eudesmin, GABA contents increased, whereas Glu contents decreased, and ratio of Glu/GABA decreased. Our results also indicated that expressions of GAD65, GABAA, and Bcl-2 were up-regulated by treating with eudesmin, whereas the caspase-3 obviously was down-regulated. In conclusion, eudesmin has significant anticonvulsant and sedative effects, and the mechanism of eudesmin may be related to up-regulation of GABAA and GAD65 expressions, and anti-apoptosis of neuron the in brain.

Genome-scale dynamic modeling of the competition between Rhodoferax and Geobacter in anoxic subsurface environments.

The advent of rapid complete genome sequencing, and the potential to capture this information in genome-scale metabolic models, provide the possibility of comprehensively modeling microbial community interactions. For example, Rhodoferax and Geobacter species are acetate-oxidizing Fe(III)-reducers that compete in anoxic subsurface environments and this competition may have an influence on the in situ bioremediation of uranium-contaminated groundwater. Therefore, genome-scale models of Geobacter sulfurreducens and Rhodoferax ferrireducens were used to evaluate how Geobacter and Rhodoferax species might compete under diverse conditions found in a uranium-contaminated aquifer in Rifle, CO. The model predicted that at the low rates of acetate flux expected under natural conditions at the site, Rhodoferax will outcompete Geobacter as long as sufficient ammonium is available. The model also predicted that when high concentrations of acetate are added during in situ bioremediation, Geobacter species would predominate, consistent with field-scale observations. This can be attributed to the higher expected growth yields of Rhodoferax and the ability of Geobacter to fix nitrogen. The modeling predicted relative proportions of Geobacter and Rhodoferax in geochemically distinct zones of the Rifle site that were comparable to those that were previously documented with molecular techniques. The model also predicted that under nitrogen fixation, higher carbon and electron fluxes would be diverted toward respiration rather than biomass formation in Geobacter, providing a potential explanation for enhanced in situ U(VI) reduction in low-ammonium zones. These results show that genome-scale modeling can be a useful tool for predicting microbial interactions in subsurface environments and shows promise for designing bioremediation strategies.