Atractylodin alleviates cancer anorexia-cachexia syndrome by regulating NPY through hypothalamic Sirt1/AMPK axis-induced autophagy.

Cancer anorexia-cachexia syndrome (CACS) is a complex syndrome associated with loss of muscle and adipose tissue and weight loss, and is a major lethal factor in the later stages of cancer. The mechanism of action of CACS is not fully understood and there are no drugs specifically approved for its treatment. Atractylodin, the main active component of Atractylodes lancea, is widely used in the treatment of digestive disorders and has the ability to reduce IL-1, IL-6 and TNF-α levels. Our results showed that gavage with Atractylodin increased body weight, muscle and fat weight and reduced tumor weight and volume as well as abnormally high serum concentrations of the muscle atrophy-causing cytokines IL-1ß, IL-6 and TNF-α in CACS model mice. RT-PCR data revealed that Atractylodin promoted the expression of the pro-feeding NPY and suppressed the expression of the anorexia POMC in the hypothalamus. Western blot results showed that Atractylodin promoted the expression of Sirt1 and p-AMPK in the hypothalamus, accompanied by an increase in autophagy. Furthermore, the Sirt1 inhibitor EX527 or AMPK inhibitor Compound C (CC) reversed Atractylodin-induced beneficial effects in CACS model mice. In hypothalamic cells subjected to glucose deprivation, Atractylodin increased NPY mRNA expression by enhancing AMPK-modulated autophagy; while EX527 or Compound C blunted Atractylodin-induced autophagy enhancement effect in vitro. In conclusion, Atractylodin can be used as an anti-cachexia drug and the underlying mechanism may involve the promotion of NPY expression by Sirt1/AMPK-regulated autophagy.

MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension.

Hypertension is considered a risk factor for a series of systematic diseases. Known factors including genetic predisposition, age, and diet habits are strongly associated with the initiation of hypertension. The current study aimed to investigate the role of miR-22-3p in hypertension. In this study, we discovered that the miR-22-3p level was significantly decreased in the thoracic aortic vascular tissues and aortic smooth muscle cells (ASMCs) of spontaneously hypertensive rats. Functionally, the overexpression of miR-22-3p facilitated the switch of ASMCs from the synthetic to contractile phenotype. To investigate the underlying mechanism, we predicted 11 potential target mRNAs for miR-22-3p. After screening, chromodomain helicase DNA-binding 9 (CHD9) was validated to bind with miR-22-3p. Rescue assays showed that the co-overexpression of miR-22-3p and CHD9 reversed the inhibitory effect of miR-22-3p mimics on cell proliferation, migration, and oxidative stress in ASMCs. Finally, miR-22-3p suppressed vascular remodeling and oxidative stress in vivo. Overall, miR-22-3p regulated ASMC phenotype switch by targeting CHD9. This new discovery provides a potential insight into hypertension treatment.

Tangzhiqing decoction attenuates cognitive dysfunction of mice with type 2 diabetes by regulating AMPK/mTOR autophagy signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tangzhiqing decoction (TZQD) is an effective prescription developed by Jiangsu Province Hospital of Chinese Medicine for the treatment of diabetes mellitus (DM) and its complications, which has a clear cerebral protective effect on mice with diabetic cognitive dysfunction, but its specific mechanism has not been well elucidated. AIMS OF THE STUDY: This study aims to verify the protection of TZQD on cognitive function in mice with type 2 diabetes mellitus (T2DM) and explore the possible underlying mechanisms. MATERIALS AND METHODS: Six active ingredients in TZQD were detected using high-performance liquid chromatography analysis. In vivo experiments, the protection of TZQD on cognitive function and hippocampal neurons in type 2 diabetes mice was verified to obtain the optimal intervention dose of TZQD. TZQD and 3-methyladenine (3 MA) respectively or jointly intervened in mice with T2DM for 12 weeks, followed by detecting the cognitive difference, hippocampus cornu ammonis 1 (CA1) region injury, and hippocampal neuronal apoptosis in each group. Simultaneously, the investigation of autophagosome formation and organelle impairment in hippocampal neurons, along with the examination of AMPK/mTOR pathway proteins and autophagy-related proteins, was conducted to elucidate the potential mechanisms, through which TZQD modulates autophagy and enhances cognitive function. In vitro experiments, TZQD-containing serum and AMPK inhibitor Compound C (CC) were used to intervene in mouse hippocampal neuron HT22 cells under high glucose environment, further clarifying the regulatory role of TZQD on the AMPK/mTOR pathway and its impact on HT22 cell apoptosis and autophagy. RESULTS: In vivo experiment results showed that TZQD had an obvious hypoglycemic effect. Different doses of TZQD could improve cognitive function and hippocampus damage in diabetes mice, with the middle dose of TZQD showing the best effect. TZQD increased the swimming speed of diabetes mice, improved their spatial recognition and memory ability, and reduced hippocampal neuronal apoptosis, Nissl body injury, and p-tau217 protein deposition. In addition, through transmission electron microscopy (TEM), immunofluorescence, and Western blot (WB) detection, TZQD significantly improved the organelle damage of hippocampal neurons in diabetes mice, promoted the formation of autophagy lysosomes, increased the expression of autophagy-related proteins like Beclin 1, LC3II/LC3I, LAMP1, and LAMP2, reduced the level of P62 and promoted autophagy flow, which, however, were all significantly weakened by 3 MA. Meanwhile, TZQD regulated the expressions of AMPK/mTOR pathway proteins. In vitro experimental study results showed that TZQD can regulate the expression ratio of p-AMPK/AMPK alpha 1 and p-mTOR/mTOR in HT22 cells under high glucose conditions and improved the morphology and vitality of HT22 cells. By employing techniques such as monodansylcadaverine (MDC) staining, Lysosomal red fluorescent probe staining, and Annexin V-FITC/PI double staining, the investigation revealed that TZQD administration resulted in enhanced autophagosome formation, preservation of a lysosomal acidic milieu, and consequent mitigation of HT22 cell apoptosis under high glucose conditions. CONCLUSIONS: TZQD can regulate the AMPK/mTOR pathway to activate autophagy to attenuate hippocampal neuronal apoptosis, thereby protecting cognitive function in diabetic mice.

Based on Bioinformatics to Explore the Mechanism of "Tangzhiqing" Decoction Alleviating Type 2 Diabetes-associated Cognitive Dysfunction in Mice by Regulating Hippocampal Neuron Apoptosis and Autophagy.

BACKGROUND: Diabetic cognitive dysfunction (DCD) is emerging as a chronic complication of diabetes that is gaining increasing international recognition. The traditional Chinese medicine (TCM) formulation, Tangzhiqing decoction (TZQ), has shown the capacity to modulate the memory function of mice with DCD by ameliorating insulin resistance. Nevertheless, the precise mechanism underlying the effects of TZQ remains elusive. METHODS: The chemical constituents of TZQ were screened using TCMSP databases, and DCDassociated disease targets were retrieved from various databases. Subsequently, core targets were identified through network topology analysis. The core targets underwent analysis using Gene Ontology (GO) functional annotations and enrichment in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Models were established through high-fat and high-glucose diet feeding along with intraperitoneal injection of streptozotocin (STZ). TZQ and metformin were administered at varying doses over 8 weeks. The Morris water maze was employed to evaluate the cognitive capabilities of each rat group, while indicators of oxidative stress and insulin were assessed in mice. Neuronal apoptosis in distinct groups of mice's hippocampi was detected using TdT-mediated dUTP Nick-End Labeling (TUNEL), and western blot (WB) analysis was conducted to assess the expression of apoptosis- and autophagy-related proteins, including Bax, Bcl2, Caspase3, Caspase8, Beclin1, ATG7, LC3, p62, and Lamp2, within the hippocampus. RESULTS: TZQ exhibited the capacity to modulate neuronal autophagy, ameliorate endoplasmic reticulum stress, apoptosis, inflammation, and oxidative stress, as well as to regulate synaptic plasticity and conduction. TZQ mitigated cognitive dysfunction in mice, while also regulating hippocampal inflammation and apoptosis. Additionally, it influenced the protein expression of autophagy-related factors such as Bax, Bcl2, Caspase3, Caspase8, Beclin1, ATG7, and LC3. Notably, this modulation significantly reduced neuronal apoptosis in the hippocampus and curbed excessive autophagy. CONCLUSION: TZQ demonstrated a substantial reduction in neuronal apoptosis within the hippocampus and effectively suppressed excessive autophagy.

Dietary saturated fatty acids increased all-cause and cardiovascular disease mortality in an elderly population: The National Health and Nutrition Examination Survey.

The influence of dietary saturated fatty acids intake on human health and cardiovascular disease (CVD) remains debated. The aim of this study was to explore the association between dietary saturated fatty acid consumption and all-cause and CVD mortality among the elderly population. Data for the participants in this study were obtained from the National Health and Nutrition Examination Survey dataset spanning the years 2003 through 2008. Information regarding mortality and the follow-up duration were extracted from the 2019 public-use linked mortality files provided by the National Center for Health Statistics. A total of 3404 participants were included in this study. The ratio of dietary saturated fatty acids to total fat was associated with the mortality from all-cause, heart disease, and cerebrovascular disease after adjusting confounding factors (P < .05). For every 10% increase in the saturated fatty acids to total fat ratio, all-cause mortality increased by 24% (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.37), the heart disease mortality increased by 26% (HR, 1.26; 95% CI, 1.05-1.52), and the cerebrovascular disease mortality increased by 67% (HR, 1.67; 95% CI, 1.14-2.45) at 10 years' follow-up. In addition, low dietary saturated fatty acids intake was associated with reduced mortality because of all-cause and heart disease after adjusting confounding factors (P < .05). In conclusion, in this elderly population, dietary saturated fatty acid intake was associated with all-cause mortality, heart disease mortality, and cerebrovascular disease mortality. Reducing saturated fatty acid intake in the diet may extend the survival rate for the elderly population. However, the difference of the effects of specific dietary saturated fatty acids with different chain lengths on mortality needs further study.

[Flower species identification and coverage estimation based on hyperspectral remote sensing data in Hulunbeier grassland].

Monitoring grassland species and area real-timely and accurately is of great significance in species diversity research, as well as in sustainable development of ecosystem. Flowers have their own unique spectral characteristics. Compared with the nutrient stage, species are more easily identified by florescence. So, florescence is a critical period for identification. In the present paper, spectral differences among such flowers as Galium verum Linn., Hemerocallis citrina Baroni, Serratula centauroides Linn., Clematis hexapetala Pall., Lilium concolor var. pulchellum, Lilium pumilum and Artemisia frigida Willd. Sp. Pl. were found, along with identification methods, by analyzing canopies spectra and parametrizing characteristics. Verification results showed that when the coverage of flowers was greater than 10%, the accuracy of identification methods would be higher than 90%. On this basis, linear unmixing model was adopted to calculate the area of flowers in quadrates. Results showed that linear unmixing model was an effective method for estimating the coverage of flowers in grassland because the accuracy was about 4%.

Association of endothelial nitric oxide synthase intron 4a/b gene polymorphisms and hypertension: a systematic review and meta-analysis.

OBJECTIVE: We conducted meta-analysis of relevant case-control trials to determine the association between endothelial nitric oxide synthase (eNOS) intron 4a/b gene polymorphisms and hypertension susceptibility. METHODS: We searched the PubMed, Cochrane, and Embase databases using relevant keywords and reviewed pertinent literature sources. All articles published up to July 2019 were considered for inclusion. Based on the qualified studies, we performed a meta-analysis of the associations between eNOS intron 4a/b polymorphisms and the risk of hypertension. RESULTS: Fourteen studies were included in this meta-analysis, including 3344 cases and 3377 controls. The eNOS intron 4a/b locus was significantly associated with increased susceptibility to hypertension (including essential hypertension) in the overall population, according to dominant, allelic, homozygote, heterozygote, and regressive models, in the mixed population according to the regressive model, and in Caucasians according to the dominant, allelic, heterozygote, and regressive models. The eNOS intron 4a/b locus was also significantly associated with increased susceptibility to essential hypertension in the mixed population according to the heterozygote model. CONCLUSION: eNOS intron 4a/b gene polymorphisms increase susceptibility to hypertension, including essential hypertension.

A meta-analysis of Alzheimer's disease's relationship with human ApoE gene variants.

PURPOSE: To explore the association between Alzheimer's disease and apolipoprotein E (ApoE). Studies on this relationship are plentiful, but they mostly suffer from the disadvantage of inadequate sample size, so we conducted this meta-analysis to assess the association between ApoE polymorphisms and AD in humans. METHOD: The research literature centered on the association between Alzheimer's disease and ApoE polymorphisms was searched using databases including EMBASE, CQVIP, Medline, Web of knowledge, PubMed, Cochrane Library, CNKI, and Wanfang Data up to July 2020. The quality of the included literature was assessed using the NOS scale. We used RevMan 5.3 statistical software for the data extraction and meta-analysis. RESULTS: A total of 569 studies were retrieved according to the search strategy and the inclusion criteria. After removing the duplicate studies and studies that did not match the topic, 155 studies were obtained. 39 publications were finally included according to the inclusion and exclusion criteria. Five of them were selected for the meta-analysis after a careful evaluation. CONCLUSION: Patients with Alzheimer's disease have a high positive rate of the ε4 allele (OR = 2.19, 95% CI: 1.38-3.48) and a low positive rate of the ε3 allele, but there is no significant association between the ApoE ε2 allele and AD (OR = 0.71, 95% CI: 0.19-2.58). The positivity rates of the ε4/ε4 and ε3/ε4 genotypes were higher in the case group (OR = 3.82, 95% CI: 1.86-7.84; OR = 2.07, 95% CI: 1.40-3.06), but the positivity rates of the ε2/ε3 and ε3/ε3 genotypes were significantly lower in the case group than in the control group (OR = 0.62, 95% CI: 0.18-2.11; OR = 0.52, 95% CI: 0.36-0.75).

[Hyperspectral remote sensing monitoring of grassland degradation].

The distributing of China's grassland is abroad and the status of grassland degradation is in serious condition. So achieving real-time and exactly grassland ecological monitoring is significant for the carbon cycle, as well as for climate and on regional economies. With the field measured spectra data as data source, hyperspectral remote sensing monitoring of grassland degradation was researched in the present article. The warm meadow grassland in Hulunbeier was chosen as a study object. Reflectance spectra of leaves and pure canopies of some dominant grassland species such as Leymus chinensis, Stipa krylovii and Artemisia frigid, as well as reflectance spectra of mixed grass community were measured. Using effective spectral feature parametrization methods, the spectral feature of leaves and pure canopies were extracted, so the constructive species and degenerate indicator species can be exactly distinguished. Verification results showed that the accuracy of spectral identification was higher than 95%. Taking it as the foundation, the spectra of mixed grass community were unmixed using linear mixing models, and the proportion of all the components was calculated, and the errors were less than 5%. The research results of this article provided the evidence of hyperspectral remote sensing monitoring of grassland degradation.

[Review of monitoring soil water content using hyperspectral remote sensing].

Soil water content is a key parameter in monitoring drought. In recent years, a lot of work has been done on monitoring soil water content based on hyperspectral remotely sensed data both at home and abroad. In the present review, theories, advantages and disadvantages of the monitoring methods using different bands are introduced first. Then the unique advantages, as well as the problems, of the monitoring method with the aid of hyperspectral remote sensing are analyzed. In addition, the impact of soil water content on soil reflectance spectrum and the difference between values at different wavelengths are summarized. This review lists and summarizes the quantitative relationships between soil water content and soil reflectance obtained through analyzing the physical mechanism as well as through statistical way. The key points, advantages and disadvantages of each model are also analyzed and evaluated. Then, the problems in experimental study are pointed out, and the corresponding solutions are proposed. At the same time, the feasibility of removing vegetation effect is discussed, when monitoring soil water content using hyperspectral remote sensing. Finally, the future research trend is prospected.