[Relationship between the percentage of energy intake from macronutrients and obesity among adult residents in 15 provinces of China in 1991-2018].

OBJECTIVE: To explore the relationship between the percentage of energy intake from macronutrients and obesity in Chinese adult residents, and analyze the cut-off values of macronutrients for predicting obesity. METHODS: Data was collected in China Health and Nutrition Survey(CHNS)in 1991-2018. Adults who participated in at least two waves of the surveys and were not obese at baseline were selected as the study subjects. Obesity was defined as body mass index(BMI)≥28.0 kg/m~2. Generalized estimating equation was used to analyze the relationship between the percentage of energy intake from macronutrients and BMI and obesity, and receiver operating characteristic curve(ROC) was used to analyze the cut-off values of percentage of energy intake from macronutrients to predict obesity. RESULTS: The percentage of energy intake from protein and fat of adult residents in 15 provinces(autonomous regions and municipalities) in China showed an increasing trend(P<0.01), and the percentage of energy intake from carbohydrate showed a decreasing trend(P<0.01) between 1991 and 2018. After adjusting for covariates, the group of percentage of energy intake from fat in 20%～30%(ß=0.05, 95%CI 0.01-0.08)and ≥30%(ß=0.15, 95%CI 0.11-0.18)were positively correlated with BMI compared with the group of percentage of energy intake from fat <20%, and the risk of obesity in 20%-30% and ≥ 30% was increased by 17%(OR=1.17, 95%CI 1.04-1.31)and 6%(OR=1.06, 95%CI 1.24-1.56), respectively. Compared with the group of the percentage of energy intake from carbohydrate < 50%, the group of 50% to 65%(ß=-0.08, 95% CI-0.11--0.05) and ≥ 65%(ß=-0.17, 95%CI-0.20--0.13) was negatively correlated with BMI, and the percentage of energy intake from carbohydrate ≥ 65% reduced the risk of obesity(OR=0.71, 95%CI 0.63-0.80). CONCLUSION: Carbohydrate intake was inversely correlated with the risk of obesity, and fat intake was positively correlated with the risk of obesity. Moderate intake of carbohydrates and reduced fat intake can prevent obesity.

Lanthanum hydroxide protects kidney through gut microbiota in a rat model of chronic kidney disease.

The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut microbiota can have beneficial effects in managing CKD, it is also recognized that dysbiosis may contribute to the progression of CKD and associated uremic complications. Our previous research has demonstrated the efficacy of lanthanum hydroxide in delaying kidney failure and preserving renal function. However, the role of lanthanum hydroxide in modulating gut microbiota in this context remains unclear. In our study, we induced CKD in rats using adenine, leading to gut microbial dysbiosis, kidney pathology, and disturbances in amino acid metabolism. In this adenine-induced CKD model with hyperphosphatemia, treatment with lanthanum hydroxide improved renal function. This improvement was associated with the restoration of gut microbial balance and an increase in urine ammonium metabolism. These results suggest that the therapeutic potential of lanthanum hydroxide in CKD may be partly due to its ability to reshape gut microbiota composition. This study underscores the significance of lanthanum hydroxide in kidney protection, attributing its benefits to the modulation of gut microbiota in a rat model of CKD.

Longitudinal Relationship between the Percentage of Energy Intake from Macronutrients and Overweight/Obesity among Chinese Adults from 1991 to 2018.

To investigate the prospective relationship between macronutrient intake and overweight/obesity, data were collected in the China Health and Nutrition Survey (CHNS) from 1991 to 2018. Adults who participated in at least two waves of the survey and were not obese at baseline were selected as the study subjects. A total of 14,531 subjects were finally included with complete data. Overweight/obesity was defined as a body mass index (BMI) ≥ 24.0 kg/m2. The generalized estimating equation (GEE) was used to analyze the relationship between the percentage of energy intake from macronutrients and BMI and overweight/obesity. The percentages of energy intake from protein and fat showed an increasing trend (p < 0.01), and the percentage of energy intake from carbohydrate showed a decreasing trend (p < 0.01) among Chinese adults between 1991 and 2018. Adjusting for covariates, the energy intake from fat was positively correlated with BMI, while the energy intake from carbohydrates was negatively correlated with BMI. The percentage of energy intake from non-high-quality protein and polyunsaturated fatty acids (PUFA) were positively correlated with overweight/obesity. In contrast, monounsaturated fatty acids (MUFA) and high-quality carbohydrates were negatively correlated with overweight/obesity. In short, fat, non-high-quality protein, saturated fatty acids (SFA), and PUFA were positively correlated with the risk of obesity, whereas higher carbohydrate, MUFA, and high-quality carbohydrate intake were associated with a lower risk of obesity. Obesity can be effectively prevented by appropriately adjusting the proportion of intake from the three major macronutrients.

3-Amide-ß-carbolines block the cell cycle by targeting CDK2 and DNA in tumor cells potentially as anti-mitotic agents.

ß-Carboline alkaloids are natural and synthetic products with outstanding antitumor activity. C3 substituted and dimerized ß-carbolines exert excellent antitumor activity. In the present research, 37 ß-carboline derivatives were synthesized and characterized. Their cytotoxicity, cell cycle, apoptosis, and CDK2- and DNA-binding affinity were evaluated. ß-Carboline monomer M3 and dimer D4 showed selective activity and higher cytotoxicity in tumor cells than in normal cells. Structure-activity relationships (SAR) indicated that the amide group at C3 enhanced the antitumor activity. M3 blocked the A549 (IC50 = 1.44 ± 1.10 µM) cell cycle in the S phase and inhibited A549 cell migration, while D4 blocked the HepG2 (IC50 = 2.84 ± 0.73 µM) cell cycle in the G0/G1 phase, both of which ultimately induced apoptosis. Furthermore, associations of M3 and D4 with CDK2 and DNA were proven by network pharmacology analysis, molecular docking, and western blotting. The expression level of CDK2 was downregulated in M3-treated A549 cells and D4-treated HepG2 cells. Moreover, M3 and D4 interact with DNA and CDK2 at sub-micromolar concentrations in endothermic interactions caused by entropy-driven adsorption processes, which means that the favorable entropy change (ΔS > 0) overcomes the unfavorable enthalpy change (ΔH > 0) and drives the spontaneous reaction (ΔG < 0). Overall, these results clarified the antitumor mechanisms of M3 and D4 through disrupting the cell cycle by binding DNA and CDK2, which demonstrated the potential of M3 and D4 as novel antiproliferative drugs targeting mitosis.

Lanthanum Hydroxide and Chronic Kidney Disease Mineral and Bone Disorder: A Rat Model.

OBJECTIVE: To investigate the pharmacological effects and molecular mechanisms of lanthanum hydroxide(LH) on ectopic mineralization of soft tissue and abnormal bone in rats with acute kidney injury(AKI). METHODS: Wistar rats were modeled by 5/6 nephrectomy. After the operation, the rats were divided into different groups, the biochemical indexes of serum collected at different times. Lanthanum hydroxide was administered by intragastric tube at doses of 0.4, 0.2, and 0.1g/kg, respectively. Rats were sacrificed in the 16th week after LH treatment. Observation of pathological changes in tissues were made by specific staining. Western Blot, Real-Time Quantitative PCR, and immunohistochemistry techniques were used to detect the impact on pathway-related proteins. RESULTS: Compared with the control group (no LH administered), the serum phosphate level of the LH group was significantly reduced (P<0.01), calcification of the thoracic aorta was reduced (P<0.05, P<0.01) (Serum biochemical tests before dosing and during drug treatment cycles), renal fibrosis was improved (P<0.01), nuclear entry of nuclear factor kappa-B (NF-κB) was reduced (P<0.01), and the expression of the smooth muscle protein 22α (SM22α) was significantly increased (P<0.01). The expression of osteogenic marker genes was decreased. In addition, compared with the controls, the receptor activator for nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio of the femur in the model group was increased (P<0.05). CONCLUSION: LH can inhibit the occurrence and development of vascular calcification and bone abnormalities in AKI rats by inhibiting the NF-κB and RANKL/OPG signaling pathways.

Design, Synthesis, and Biological Evaluation of Two Series of Novel A-Ring Fused Steroidal Pyrazines as Potential Anticancer Agents.

BACKGROUND: Increasingly, different heterocyclic systems have been introduced into the steroid nucleus to significantly enhance the antitumor activities of steroid molecules. However, in this study, few literature precedents describing the pyrazine heterocyclic-condensed modification to an A-ring of steroid monomers were found, although the pyrazine group is thought to be essential for the potent anticancer activity of clinically relevant drugs and natural steroid dimers. METHODS AND RESULTS: Two series of novel A-ring fused steroidal pyrazines were designed and efficiently synthesized from commercially available progesterone via key α-ketoenol intermediates. Through a cell counting kit-8 cytotoxic assay of 36 derivatives for three tumor cells, 14 compounds displayed significant antiproliferative activity compared to 5-fluorouracil, especially for human prostatic tumor cells (PC-3) in vitro. Further mechanistic studies indicated that the most active compound, 12n (IC50, 0.93 µM; SI, 28.71), could induce the cell apoptosis of PC-3 cells in a dose-dependent manner and cause cell cycle arrest in the G2/M phase. The molecular docking study suggested that compound 12n fitted the active sites of cytochrome P450 17A1 (6CIZ) well. CONCLUSIONS: 12n might serve as a promising lead compound for the development of novel anticancer drugs. This facile ring-closing strategy may provide a novel and promising avenue for the cycloaddition reaction of the steroidal skeleton through α-ketoenol intermediates.

Wacker-Type Oxidation Using an Iron Catalyst and Ambient Air: Application to Late-Stage Oxidation of Complex Molecules.

A practical and general iron-catalyzed Wacker-type oxidation of olefins to ketones is presented, and it uses ambient air as the sole oxidant. The mild oxidation conditions enable exceptional functional-group tolerance, which has not been demonstrated for any other Wacker-type reaction to date. The inexpensive and nontoxic reagents [iron(II) chloride, polymethylhydrosiloxane, and air] can, therefore, also be employed to oxidize complex natural-product-derived and polyfunctionalized molecules.

Terahertz identification and quantification of neurotransmitter and neurotrophy mixture.

Terahertz spectroscopy has been widely used for investigating the fingerprint spectrum of different substances. For cancerous tissues, the greatest difficulty is the absorption peaks of various substances contained in tissues overlap with each other, which are hard to identify and quantitative analyze. As a result, it is very hard to measure the presence of cancer cell and then to diagnose accurately. In this paper, we select three typical neurotransmitters (γ-aminobutyric acid, L-glutamic acid, dopamine hydrochloride) and two typical metabolites (inositol and creatine) in neurons to measure their terahertz spectra with different mixture ratios. By choosing characteristic absorption peaks, removing baseline and using the least square method, we can identify the components and proportions of each mixture, where the goodness of fit to practical situation is up to 94%. These results provide important evidences for identifying nerve substances and obtaining exact quantitative analysis.