Use of Network Pharmacology and Molecular Docking to Investigate the Mechanism by Which Ginseng Ameliorates Hypoxia

Hypoxia is a common pathological process in various clinical diseases and is characterized by abnormal changes in metabolism, function, and morphological structure of tissues resulting from insufficient oxygen supply or oxygen barriers in tissues. In particular, hypoxia in vital organs such as the brain and heart is an important cause of death;. The prevention of tissue hypoxia and the

Pterostilbene Ameliorates Glycemic Control,Dyslipidemia and Liver Injury in Type 2 Diabetes Rats

Type 2 diabetes mellitus(T2DM)is typified by the increment of chronic blood glucose levels that is caused by an absolute and/or a relative deficiency of insulin,accounts for 90%of diabetes and causes a range of complications[1].

Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system

Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate(4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time,the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2-/-mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment.Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction,ameliorate local inflammation for more predictable periodontitis.

Rosiglitazone ameliorates diffuse axonal injury by reducing loss of tau and up-regulating caveolin-1 expression

Rosiglitazone up-regulates caveolin-1 levels and has neuroprotective effects in both chronic and acute brain injury. Therefore, we postulated that rosiglitazone may ameliorate diffuse axonal injury via its ability to up-regulate caveolin-1, inhibit expression of amyloid-beta precursor protein, and reduce the loss and abnormal phosphorylation of tau. In the present study, intraperitoneal injection of rosiglitazone significantly reduced the levels of amyloid-beta precursor protein and hyperphosphorylated tau（phosphorylated at Ser^（404）（p-tau（S^（404）））, and it increased the expression of total tau and caveolin-1 in the rat cortex. Our results show that rosiglitazone inhibits the expression of amyloid-beta precursor protein and lowers p-tau（S^（404）） levels, and it reduces the loss of total tau, possibly by up-regulating caveolin-1. These actions of rosiglitazone may underlie its neuroprotective effects in the treatment of diffuse axonal injury.

Eotaxin-2 blockade ameliorates experimental autoimmune encephalomyelitis

AIM： To study the effect of blocking the eo-2 pathwaon the development and severity of experimental autoimmune encephalomyelitis （EAE）. METHODS： We produced mAb directed against eo-2named D8. MOG35-55 induced-EAE mice were dailintravenously injected with either 25 μg or 100 μg D8or with vehicle control alone [phosphate-buffered saline（PBS）], starting from day 0 post immunization and weremonitored for EAE clinical score （n = 10 in each group）Mice were sacrifced on day 58 and their sera were assessed for the presence of anti-myelin oligodendrocyteglycoprotein （anti-MOG） antibodies autoantibodies, awell as for the profle of pro-infammatory cytokines andchemokines. Histological analysis of brain sections waperformed by hematoxylin and eosin staining.RESULTS： Daily treatment of EAE induced mice with D8 signifcantly decreased the severity of EAE symp-toms. Treatment with both concentrations of D8 ame-liorated EAE symptoms compared to PBS treated mice, starting from day 42 post immunization （0.89 ± 0.35 in D8 25 μg and D8 100 μg treated groups vs 2.11 ± 0.38 in the PBS treated group, P = 0.03）. A signifcant im-provement in EAE clinical score compared to total IgG treated mice was observed with the higher concentra-tion of D8 （0.81 ± 0.38 in D8 100 μg treated group vs 2.11 ± 0.31 in IgG1 treated group, on day 56 post immunization, P = 0.04）. D8 treated mice with EAE did not signifcantly exhibit lower sera levels of anti-MOG autoantibodies compared to IgG-treated mice. How-ever, they expressed lower sera levels of the pro-in-fammatory cytokines： tumor necrosis factor （7.8 ± 0.2 pg/mL in D8 100 μg treated mice vs 19.9 ± 3.4 pg/mL in IgG treated mice, P = 0.005） and interferon-gamma （1.4 ± 0.6 pg/mL in D8 100 μg treated mice vs 3.6 ± 0.4 pg/mL in IgG treated mice, P = 0.02）, as well as reduced levels of the chemokine macrophage che-moattractant protein-1 （27.2 ± 3.1 pg/mL in D8 100 μg treated mice vs 63.7 ± 12.3 pg/mL in IgG treated mice, P = 0.03）. These fndings indicate that blocking the eo-2 pathway in EAE may affect not only eosino-phil infltration into the central nervous system （CNS）, but also have an effect on monocytes and T cells, but not humoral, mediated responses. Histological analysis of the brains of D8 treated mice with EAE support that this treatment decreases immune cells infltrates in the CNS.CONCLUSION： Taken together, these fndings suggest a role for eo-2 in EAE pathogenesis and consequen-tially may support a therapeutic potential of anti-eo-2 neutralizing mAb in multiple sclerosis.

Copper Ameliorates Fluoride Toxicity in Fluoride and Molybdenum Fed Rabbits

Hydrofluorosis is a major public health problem in India, which is aggravated by presence or absence of some minerals in water or food. Fluoride by itself or in combination with other elements like molybdenum （Mo） in diet or water changes excretion/retention of bone minerals. Sorghum and pearl millet grown and consumed in fluorosis endemic areas contained significantly higher amounts of Mo than that grown in non-fluorotic areas in India.

3-56 Curcumin Ameliorates Heavy Ion Irradiation-induced Learning and Memory De cits Through Enhancing Nrf2 Antioxidant Signaling Pathways

Oxidative stress is one of the major mechanisms implicated in carbon ion irradiation[1;2]. Curcumin is a naturalphenolic compound with impressive antioxidant properties[3]. What's more, curcumin is recently proved to exertradioprotective effect. In vivo, we investigated the protective effects of curcumin against 12C6+radiation-inducedcerebral injury.Our results showed that 4 Gy heavy ion radiation-induced spatial strategy and memory decline (Fig. 1), reductionof brain Superoxide Dismutase (SOD) activity levels, were all consistently improved by curcumin, as well as theaugmentation of cerebral malonaldehyde (MDA), was lowered by curcumin (Fig. 2). Furthermore, both the cerebralcells Nuclear erythroid 2-related factor 2 (Nrf2) protein and three typically recognized Nrf2 downstream genes,NADP(H) quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and -glutamyl cysteine synthetase (-GCS) were consistently up-regulated in curcumin-pretreated mice (Fig. 3).

Osteocyte viability and bone density in cadmium chloride-induced osteoporosis ameliorated with Pilostigma thonningii stem bark-extracted D-3-O-methy-chiroinositol

Background : This study examined the ameliorative effect of D-3-O-methylchiroinositol, isolated from the stem bark of Piliostigma thonningii, on cadmium chloride-induced osteoporosis in male Wistar rats. Methods : Thirty-six rats were assigned to three treatment groups(n = 12). Group A(2 mL distilled water), group B:(2.5 mg/kg b.w. CdCl_2) and group C:(2.5 mg/kg b.w. CdCl_2 and D-3-O-methyl-chiroinositol 2 mg/kg b.w.). Bone ash, calcium, phosphate, magnesium, and zinc content, as well as bone histological changes were determined at the end of months 1, 2, and 3. Results : There were significant differences( P ≤ 0.05) in the weight of the cervical, tibia, and femoral bones in all groups. The serum concentration of CdCl_2 was significantly different across the three groups with time. There was significant variation( P < 0.005) in the mean bone ash across groups. The concentration of OH-proline was significantly different( P < 0.0001) across groups. There were significant differences( P < 0.0001) in bone calcium, magnesium, zinc, and phosphorus concentrations. Histology revealed high levels of bone mineralisation in the CdCl_2-treated group, indicative of osteoporosis with hypertrophied osteocytes, while the femur of Wistar rats treated with D-3-O-methyl-chiroinositol showed bone trabeculae and viable osteocytes. Conclusion : The study concluded that D-3-O-methyl-chiroinositol extract from Piliostigma thionningii stem bark ameliorated cadmium chloride-induced osteoporosis in male Wistar rats.

Zhuangyao Jianshen pill(壮腰健肾丸) ameliorates testosterone-induced benign postatic hyperplasia in rats

OBJECTIVE:To determine the therapeutic effects of the Zhuangyao Jianshen pill(壮腰健肾丸,ZYJSP)against benign prostatic hyperplasia(BPH)and investigate the underlying mechanism.METHODS:Forty-eight male Sprague-Dawley rats were randomly divided into six groups:Control group,BPH model group,finasteride-treated group,ZYJSP low,medium and high dose groups.Except for the control group,40 rats were castrated and injected with testosterone propionate(TP)for 28 consecutive day to induce BPH.Meanwhile,the corresponding drugs were administered by gavage.The prostate wet weight,prostate index(PI),and the histopathological changes in the prostate were measured as the basis for examining the efficacy of ZYJSP against BPH.Levels of the serum sex hormones,oxidative stress markers,inflammatory markers,renal function markers,growth factors,and Cyclin D1 expression in prostate were measured to characterize the therapeutic mechanism of ZYJSP against BPH.RESULTS:ZYJSP administration significantly reduced prostate wet weight and PI and ameliorated histological changes of the prostate in TP-treated castrated rats.TP markedly increased the levels of creatinine,blood urea nitrogen and growth factors in the serum as well as the expression of the Cyclin D1 in the prostate.Most of these markers were significantly decreased by ZYJSP.ZYJSP significantly restored the dysregulation of testosterone,estradiol,and dihydrotestosterone caused by TP.Furthermore,ZYJSP relieved TP-induced prostate injury and exhibited both anti-inflammatory and anti-oxidant activity by decreasing interleukin-6,interleukin-8,and malondialdehyde levels and increasing the activity of superoxide dismutase in the serum.CONCLUSION:These findings indicate that ZYJSP can effectively ameliorate BPH induced by TP in castrated rats,and the underlying mechanism might be related to regulating sex hormone balance,reducing oxidative stress,and inhibiting the inflammatory response.

IL-6R blockade by chikusetsusaponin IVa butyl ester inhibits Th17 cell differentiation and ameliorates collagen-induced arthritis

Interleukin(IL)-6 is central to the pathogenesis of rheumatoid arthritis(RA).1 IL-6 receptor(IL-6R)blockade is an effective treatment strategy for RA based on the clinical efficacy of tocilizumab.However,serious infections are the most frequent adverse events associated with long-term monotherapy with tocilizumab,an exogenous biomacromolecule.2 Novel small-molecule IL-6R inhibitors with fewer deleterious side effects could therefore have potential as RA treatments.We previously identified chikusetsusaponin IVa butyl ester(CS)as a natural small-molecule IL-6R antagonist.3 Here,we assessed the effects of CS on a mouse model of collagen-induced arthritis(CIA)to evaluate its therapeutic potential against RA.The results showed that CS ameliorated arthritis in CIA mice by inhibiting T-helper 17(Th17)cell differentiation and could serve as a novel agent for treating RA.

tRF-Gln-CTG-026 ameliorates liver injury by alleviating global protein synthesis

tsRNAs(tRNA-derived small RNAs),as products of the stress response,exert considerable influence on stress response and injury regulation.However,it remains largely unclear whether tsRNAs can ameliorate liver injury.Here,we demonstrate the roles of tsRNAs in alleviating liver injury by utilizing the loss of NSun2(NOP2/Sun domain family,member 2)as a tsRNAs-generating model.Mechanistically,the loss of NSun2 reduces methyluridine-U5(m^(5)U)and cytosine-C5(m^(5)C)of tRNAs,followed by the production of various tsRNAs,especially Class I tsRNAs(tRF-1s).Through further screening,we show that tRF-Gln-CTG-026(tG026),the optimal tRF-1,ameliorates liver injury by repressing global protein synthesis through the weakened association between TSR1(pre-rRNA-processing protein TSR1 homolog)and pre-40S ribosome.This study indicates the potential of tsRNA-reduced global protein synthesis in liver injury and repair,suggesting a potential therapeutic strategy for liver injury.

How Do Herbal Medicines Tonify the Kidney and Ameliorate the Marrow Microenvironment Work on Hemopoiesis

Herbal Medicines used to tonify Kidney and ameltorate the marrow microenvironmentwere applied in the treatment of 50 patients of aplastic anemia. Stanazol was also used to some cases.Forty-one cases (82. 0 % )responded well. It is significantly better than the 56. 5 % response among thosetreated with stanazol alone. Experimentally, the herbal medicines appear to stimulate hemopoietic pro-genitor cell proliferation, improve the marrow microenyironment and repair marrow damage induced bycyclophosphamide in vivo. The hemopoietic promoting effect might be partly due to the desialation of themarrow stroma cells. The herbal medicines also exert a positive effect on immune system by increasingleukocyte phagocytic activity and elevating the interleukin-2 production. Moreover , the decrease of super-oxide dismutase resulting from cyclophosphamide injection could be reversed by the use of the herbalmedicines. In conclusion, to tonify the Kidney and ameliorate marrow microenvironment medicines pro-duce broad biological results that are beneficial to the body.

PENTOXIFYLLINE AMELIORATES PULMONARY DAMAGE CAUSED BY STREPTOCOCCUS PNEUMONIAE INFECTION IN MOUSE

Streptococcus pneumoniae stimulated mouse peritoneal macrophagc to release tumor necrosis factor-α (TNFα) in vitro. When penicillin was added into the medium with bacteria, TNFα release was accelerated. Pentoxifylline (PTX), a phosphodiesterase inhibitor, significantly attenuated TNFα release caused either by Streptococcus pneumoniae or by its lysates. In this experiment, 150 Kunming mice were infected with Streptococcus peumoniae through inspiration. Dynamic changes of TNFα concentration in serum and bronchoalveolar lavage fluid were determined, and pulmonary pathological changes were also observed. It was found that PTX significantly attenuated TNFα activity in serum and bronchoalveolar lavage fluid, and inhibited white blood cell chemotaxis, emigration and infiltration. In conclusion, Streptococcus pneumoniae infection stimulates the release of TNFα which is probably the major mediater that causes tissue damage during Streptococcus pneumoniae infection. The mechanism is probably that Steptococcus pneumoniae and its lysates activate TNFα gene transcription. As penicillin accelerates TNFα release, treatment with penicillin alone may aggravate the tissue damage. Combined treatment with PTX may be more reasonable.

NDGA ameliorates experimental autoimmune encephalomyelitis via the regulation of IL-6,IL-17 and TGF-b

Objective To investigate the effets of nordihydroguaiaretic acid(NDGA)on the expression of IL-6,IL-17and TGF-βin mice with experimental autoimmune encephalomyelitis(EAE).Methods C57BL/6 mice were immunized with MOG35-55 to induce EAE.The 54 mice were randomly and equally divided into control group,model group and treatment group.Mice in treatment

Combined Use of Alkaline Slag and Rapeseed Cake to Ameliorate Soil Acidity in an Acid Tea Garden Soil

Rapeseed cake （RC）, the residue of rapeseed oil extraction, is effective for improving tea （Camellia sinensis） quality, especially taste and aroma, but it has limited ability to ameliorate strongly acidic soil. In order to improve the liming potential of RC, alkaline slag （AS）, the by-product of recovery of sodium carbonate, was incorporated. Combined effects of different levels of RC and AS on ameliorating acidic soil from a tea garden were investigated. Laboratory incubations showed that combined use of AS and RC was an effective method to reduce soil exchangeable acidity and A1 saturation and increase base saturation, but not necessarily for soil pH adjustment. The release of alkalinity from the combined amendments and the mineralization of organic nitrogen increased soil pH initially, but then soil pH decreased due to nitrifications. Various degrees of nitrification were correlated with the interaction of different Ca levels, pH and N contents. When RC was applied at low levels, high Ca levels from AS repressed soil nitrification, resulting in smaller pH fluctuations. In contrast, high AS stimulated soil nitrification, when RC was applied at high levels, and resulted in a large pH decrease. Based on the optimum pH for tea production and quality, high ratios of AS to RC were indicated for soil acidity amelioration, and 8.0 g kg-1 and less than 2.5 g kg-1 were indicated for AS and RC, respectively. Further, field studies are needed to investigate the variables of combined amendments.

Electricity Generation from Heatwaves

We chose a definition of heatwaves (HWs) that has ~4-year recurrence frequency at world hot spots. We first examined the 1940-2022 HWs climatology and trends in lifespan, severity, spatial extent, and recurrence frequency. HWs are becoming more frequent and more severe for extratropical mid- and low-latitudes. To euphemize HWs, we here propose a novel clean energy-tapping concept that utilizes the available nano-technology, micro-meteorology knowledge of temperature distribution within/without buildings, and radiative properties of earth atmosphere. The key points for a practical electricity generation scheme from HWs are defogging, insulation, and minimizing the absorption of infrared downward radiation at the cold legs of the thermoelectric generators. One sample realization is presented which, through relay with existing photovoltaic devices, provides all-day electricity supply sufficient for providing air conditioning requirement for a residence (~2000-watt throughput). The provision of power to air conditioning systems, usually imposes a significant stress on traditional city power grids during heatwaves.

Correlation Dimension in Fault Diagnosis of 600 MW Steam Turbine Generator

GP algorithm of correlation dimension computation is ameliorated which overcomes the shortage of traditional one. Improved process of GP algorithm takes the influence of temporal correlative pairs of points on correlation dimension into account and promotes the computational efficiency prominently. Iterative SVD method is applied to remove the influence of noise on the result of correlation dimension. The faults of steam flow turbulence and oil film disturbance which occur in 600 MW Steam Turbine Generator are analyzed and whose correlation dimensions are computed. More distinct quantitative index than FFT is gained to distinguish two faults and it’s of little importance to apply correlation dimension to study the influence of various factors on steam flow turbulence fault for nonexistence of convergent floor in correlation integral curve, which presents a new way to learn the operational function of large capacity steam turbine generator and carry out comprehensive condition monitoring.

Therapeutic effects of mGluRs antagonists on diffuse brain injury in rats

Objective To study the neuroprotective effects of antagonist or agonist of metabotropic glutamate receptors (mGluRs) on diffuse brain injury (DBI) in rats. Methods All rats were randomly divided into four groups and injected intraccerebro-ventricularly with 10 μl of MCPG (Group Ⅰ ,antagonists),DCG-Ⅳ (Group Ⅱ ,agonists) or L-AP4 (Group Ⅲ , mGluRs) respectively 1 hour after DBI, while all control rats were injected with normal saline instead. Then, the motor and cognitive performance, the water content and the number of injured neurons were recorded at different intervals after DBI. Results There was no significant change in the mortality of rats with DBI after treatment with MCPG,DCG-Ⅳ or L-AP4. MCPG or DCG-Ⅳ .especially MCPG could ameliorate the mortor and cognitive performance and decrease water contents and the damaged neurons in the parietal cortex of the rats with DBI (P【0.05). However,L-AP4 did not have the effect above mentioned (P 】 0. 05 ). Conclusion MCPG and DCG-Ⅳ, especially MCPG,

Amelioration of Saline-Sodic Soils with Tillage Implements and Sulfuric Acid Application

Amelioration of saline-sodic soils through land preparation with three tillage implements （disc plow, rotavator and cultivator） each followed by application of sulfuric acid at 20% of gypsum （CaSO4-2H2O） requirement or no sulfuric acid application during crop growth period was evaluated in a field study for 2.5 years at three sites, i.e., Jhottianwala, Gabrika （Thabal）, and Thatta Langar, in Tehsil Pindi Bhattian, Hafizahad District, Pakistan. Within 2.5 years, there was a decrease in the salinity parameters measured （electrical conductivity, pH, and sodium adsorption ratio）, with a gradual increase in rice and wheat grain yields. It was observed that the disc plow, which not only ensured favorable yields but also helped improve soil health at all the three sites, was the most effective tillage implement. Also, application of sulfuric acid resulted in higher yields and promoted rapid amelioration of the saline-sodic soils.

Effects of different plantation types on soil properties after vegetation restoration in an alpine sandy land on the Tibetan Plateau, China

Large areas of Artemisia ordosica Krasch., Caragana korshinskii Kom., and Caragana intermedia Kuang and H. C. Fu plantations were established on moving sand dunes in the Gonghe Basin （northeastern Tibetan Plateau） for vegetation restoration. Elevating our understanding of the changes in soil characteristics after the establishment of different plantation types can be useful in the context of combating deserdfication. To assess the effects of these plantation types on the restoration of sandy land, we measured soil physical-chemical properties at four depths （0-5, 5-10, 10-20, and 20-50 cm） in each of the three plantation types and also in non-vegetated moving sand dunes （as control sites）. Generally, the establishment of A. ordosica, C korshinskii and C intermedia plantations on sand dunes has greatly ameliorated soil quality in the Gonghe Basin. Specifically, relative to the moving sand dunes, shrub plantation has increased the silt and clay contents, total porosity and water holding capacity, soil organic matter, total nitrogen, total phosphorus and total potassium contents. The calculated soil quality index suggested that in the Gonghe Basin, C. intermedia is the best choice for soil amelioration. In all the three plantation types, soil amelioration mainly occurred in the shallow depths.