Pharmaceutical Care by Clinical Pharmacists can Effectively Improve the Use of Antibacterials and Hepatoprotective Drugs during Perioperative Period in Urology Department: A Retrospective Study.

BACKGROUND: The management of medication for patients undergoing urological surgery is a subject of ongoing controversy, especially in elucidating the effect of clinical pharmacists on medication rationality. This study aims to assess the influence of clinical pharmacist service on the utilization of antibacterial and hepatoprotective drugs in urological surgery patients during the perioperative period. METHODS: Patients undergoing urological surgery in our hospital from January 2020, to January 2023, were consecutively selected. The patients were divided into control group (routine procedure) and observation group (routine procedure + clinical pharmacist service). The baseline data were balanced by 1:1 propensity score matching (PSM). The t test and chi-square test were used to compare the drug use, adverse reactions, and hospitalization-related indicators between the two groups. RESULTS: A total of 292 patients were included, with 100 patients in each group after PSM. No significant difference was found in the baseline data between the two groups (p > 0.05). The rationality of drug use (drug type, administration time, course of treatment, and combination) in the observation group was significantly better than that in the control group (χ2 = 8.489, 10.607, 10.895, 10.666; p = 0.004, 0.001, 0.001, 0.001). The incidence of adverse reactions (6.00%) and postoperative complications (7.00%) was significantly lower (χ2 = 4.903, 5.531; p = 0.027, 0.019). The length of hospital stay and total cost were similar (p > 0.05). The use time and cost of antibacterial and hepatoprotective drugs in the observation group were lower than those in the control group (t = 2.935, 3.450, 3.243, 3.532; p = 0.004, 0.001, 0.001, 0.001). The types and rates of antibacterial and hepatoprotective drugs in the observation group were significantly lower than those in the control group (p < 0.05). CONCLUSIONS: Clinical pharmacist service can effectively improve the rationality of drug use in urological surgery patients and reduce adverse reactions and postoperative complications, hence its clinical promotion value.

Evaluating the Anti-Melanoma Effects and Toxicity of Cinnamaldehyde Analogues.

Cinnamaldehyde (CA) showed potent activity against melanoma in our previous study, and the structure of unsaturated aldehydes is envisaged to play a role. Nevertheless, its limited drug availability restricts its clinical application. Therefore, a series of CA analogues were synthesized to evaluate their anti-melanoma activities across various melanoma cell lines. These compounds were also tested for their toxicity against the different normal cell lines. The compound with the most potential, CAD-14, exhibited potent activity against the A375, A875 and SK-MEL-1 cells, with IC50 values of 0.58, 0.65, and 0.82 µM, respectively. A preliminary molecular mechanism study of CAD-14 indicated that it could inhibit the p38 pathway to induce apoptosis, and suppress tumor growth by inhibiting the expression of ENO1. Furthermore, an acute toxicity study depicted that CAD-14 has better safety and tolerability than CA in vivo. These findings indicate that CAD-14 might be a lead compound for exploring effective anti-melanoma drugs.

6-Shogaol Exhibits a Promoting Effect with Tax via Binding HSP60 in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) is a prevalent malignant tumor with high morbidity and mortality rates worldwide. Although surgical resection, adjuvant radiotherapy/chemotherapy, and targeted molecular therapy are the cornerstones of NSCLC treatment, NSCLC is associated with high recurrence rates and drug resistance. This study analyzed the potential targets and pathways of 6-Shogaol (6-SH) in NSCLC, showing that 6-SH binds to heat-shock 60 kDa protein (HSP60) in A549 cells, induces cell apoptosis, and arrests the cell cycle possibly by disrupting the mitochondrial function. HSP60 was identified as the target of 6-SH and 6-SH-induced HSP60 degradation which was mediated by the proteasome. The binding of 6-SH with HSP60 altered its stability, inhibited the ERK, Stat3, PI3K, Akt, and mTOR signaling pathways, and Tax acted synergistically with 6-SH, indicating that 6-SH could be developed as a potential therapeutic agent for an NSCLC treatment.

Correction: Gut microbiome analysis of type 2 diabetic patients from the Chinese minority ethnic groups the Uygurs and Kazaks.

[This corrects the article DOI: 10.1371/journal.pone.0172774.].

Gut microbiome analysis of type 2 diabetic patients from the Chinese minority ethnic groups the Uygurs and Kazaks.

The gut microbiome may have an important influence on the development of diabetes mellitus type 2 (DM2). To better understand the DM2 pandemic in ethnic minority groups in China, we investigated and compared the composition and richness of the gut microbiota of healthy, normal glucose tolerant (NGT) individuals and DM2 patients from two ethnic minority groups in Xinjiang, northwest China, the Uygurs and Kazaks. The conserved V6 region of the 16S rRNA gene was amplified by PCR from the isolated DNA. The amplified DNA was sequenced and analyzed. An average of 4047 high quality reads of unique tag sequences were obtained from the 40 Uygurs and Kazaks. The 3 most dominant bacterial families among all participants, both healthy and DM2 patients, were the Ruminococcaceae, Lachnospiraceae, and Enterobacteriaceae. Significant differences in intestinal microbiota were found between the NGT individuals and DM2 patients, as well as between the two ethnic groups. Our findings shed new light on the gut microbiome in relation to DM2. The differentiated microbiota data may be used for potential biomarkers for DM2 diagnosis and prevention.

[Effect of protein intervention on amino acid metabolism spectrum of Qi and Yin deficiency type 2 diabetic rats].

To study the effect of plant protein and animal protein on amino acid metabolism spectrum of Qi and Yin deficiency type 2 diabetic rats. 110 male SD rats were randomly divided into blank group (n=10), diabetic model group (n=20), disease-symptoms group (n=80). The rats of blank group received ordinary feeding, while other groups were fed with high sugar and fat diets. During the whole process of feeding, rats of disease-symptoms group were given with Qingpi-Fuzi (15.75 g•kg⁻¹) once a day through oral administration. Five weeks later, the rats were given with a low dose of STZ (40 mg•kg⁻¹) by intraperitoneal injection to establish experimental diabetic models. Then the models were randomly divided into disease-symptoms group 1 (Qi and Yin deficiency diabetic group, 15.75 g•kg⁻¹), disease-symptoms group 2 (plant protein group, 0.5 g•kg⁻¹), disease-symptoms group 3 (animal protein group, 0.5 g•kg⁻¹), disease-symptoms group 4 (berberine group, 0.1 g•kg⁻¹). The drugs were given for 4 weeks by gavage administration. After 4 weeks of protein intervention, the abdominal aortic blood was collected and serum was isolated to analyze its free amino acid by using AQC pre-column derivatization HPLC and fluorescence detector. Four weeks after the protein intervention, plant protein, animal protein and berberine had no obvious effect on body weight and blood sugar in type 2 diabetic rats. As compared with animal protein group, histidine and proline（P<0.01）, serine, glycine, threonine, alanine, tyrosine, valine, methionine, bright+isoleucine, phenylalanine and lysine（P<0.05）changed a lot in rats serum of plant protein group.The results showed that gavage administration of protein would produce effects on amino acid metabolism of Qi and Yin deficiency type 2 diabetic SD rats. Symbolic differential compounds could be found through metabonomics technology, providing experimental basis for early warning of type 2 diabetes and diagnosis of Qi and Yin deficiency syndrome.

MicroRNA-130a expression is decreased in Xinjiang Uygur patients with type 2 diabetes mellitus.

AIMS: MicroRNAs play important roles in energy metabolism, insulin synthesis, insulin transport and the development of diabetes. This study aims to investigate the expression and effect of microRNA-130a in Uygur patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Peripheral blood and omental adipose tissues were collected from individuals with normal glucose tolerance and patients with T2DM. The microRNA expression profile of peripheral blood was established by microarray analysis. The differentially expressed microRNAs and possible target genes were identified by bioinformatics analysis. MicroRNA-130a mimics and inhibitors were transfected into 3T3-L1 preadipocytes. RESULTS: Our results showed that microRNA-130a expression level was significantly decreased in peripheral blood and omental adipose tissues of T2DM patients (P < 0.01). Peroxisome proliferator-activated receptors γ (PPARγ) were predicted as target genes of microRNA-130a. This prediction was verified by the results that PPARγ mRNA expression in omental adipose tissues of T2DM patients were significantly increased (P < 0.01). The glucose consumption level after microRNA-130a transfection was significantly decreased (P < 0.05). And, microRNA-130a mimics inhibited PPARγ expression at both mRNA and protein level, further suggesting that PPARγ is a target gene of microRNA-130a. Additionally, adiponectin, lipoprotein lipase, CCAAT enhancer binding protein α, and the downstream genes of PPARγ, were significantly decreased after microRNA-130a mimics transfection. CONCLUSIONS: In conclusion, microRNA-130a is decreased in Uygur patients with T2DM and it may play a role in T2DM through targeting PPARγ.

Ellagic Acid Reduces Adipogenesis through Inhibition of Differentiation-Prevention of the Induction of Rb Phosphorylation in 3T3-L1 Adipocytes.

Ellagic acid (EA) present in many fruits and nuts serves as antiproliferation, anti-inflammatory, and antitumorigenic properties. However, the effect of EA on preadipocytes adipogenesis and its mechanism(s) have not been elucidated. The present study was designed to examine the effect of EA on adipogenesis in 3T3-L1 preadipocytes and underlying mechanism(s) of action involved. Data show that EA administration decreased the accumulation of lipid droplets. The inhibition was diminished when the addition of EA was delayed to days 2-4 of differentiation. Clonal expansion was reduced in the presence of EA. FACS analysis showed that EA blocked the cell cycle at the G1/S transition. EdU incorporation also confirmed that EA refrained cell from entering S phase. Our data also revealed that the differentiation-induced protein expression of Cyclin A and phosphorylation of the retinoblastoma protein (Rb) were impaired by EA. Differentiation-dependent expression and DNA-binding ability of C/EBP α were also inhibited by EA. Alterations in cell cycle-associated proteins may be important with respect to the antiadipogenic action of EA. In conclusion, EA is capable of inhibiting adipogenesis in 3T3-L1 adipocytes possibly through reduction of Cyclin A protein expression and Rb phosphorylation. With the blocking of G1/S phase transition, EA suppresses terminal differentiation and lipid accumulation in 3T3-L1 adipocytes.

Lipopolysaccharides reduce adipogenesis in 3T3-L1 adipocytes through activation of NF-κB pathway and downregulation of AMPK expression.

Lipopolysaccharides (LPS) from the outer membrane of Gram-negative bacteria serve as endotoxin to exert potent immune responses. However, the effect of LPS on adipogenesis has not been elucidated. The present study was designed to examine the effect of LPS on adipogenesis in 3T3-L1 preadipocytes and possible mechanism(s) of action involved. Our results revealed that LPS challenge significantly suppressed adipogenesis in 3T3-L1 preadipocytes mainly through downregulated expression of the late adipogenic markers PPARγ and aP2 as well as AMP-activated protein kinase (AMPK) expression and activity. As an inflammatory factor, LPS was found to lead to an overt reduction in IκBα levels compared with the time-matched controls, consolidating its pro-inflammatory property in 3T3-L1 preadipocytes. Our data also revealed that LPS retarded adipogenesis, the effect of which was partially reversed by the selective inhibitor of IKKß. IκBα was found to be involved in the anti-adipogenic effect of LPS. In conclusion, LPS is capable of inhibiting adipogenesis in 3T3-L1 adipocytes possibly through activation of NF-κB and inhibition of AMPK. With the activation of NF-κB pathway and inhibition of AMPK, LPS suppresses C/EBP α DNA-binding activity and the expression of late adipogenic markers PPARγ and aP2.

Prevalence of metabolic syndrome, insulin resistance, impaired fasting blood glucose, and dyslipidemia in Uygur and Kazak populations.

This study was designed to evaluate the prevalence of the metabolic syndrome (MetS), impaired fasting blood glucose (IFG), insulin resistance (IR), hypertriglyceridemia (HTG), and low high-density lipoprotein cholesterol (HDL-C) in adult Uygur and Kazak populations. Questionnaires, blood pressure, anthropometric measurement, and fasting glucose were evaluated. The age-adjusted prevalence of MetS and IFG was 3.43- and 1.47-fold higher, respectively, in Uygurs compared with Kazaks. The prevalence of IR and HTG was 1.33- and 2.22-fold higher, respectively, in Uygurs compared with Kazaks. In addition, the prevalence of low HDL-C was 4.05-fold higher in Uygurs compared with Kazaks. These data depicted greater risk for cardiometabolic syndrome in Uygurs compared with Kazaks. In addition, all prevalence with the exception of low HDL-C was greater in men compared with women in both ethnic groups. For body mass index (BMI)<24, 24 to 28, and ≥28 kg/m2, the prevalence of MetS, HTG, and low HDL-C was higher in Uygurs than Kazaks at the same BMI level. For individuals with a BMI between 24 and 28, the prevalence of IR but not IFG was significantly greater in Uygurs than Kazaks. At BMI≥28, neither IFG nor IR was overtly different between the two ethnic groups.

The prevalence of type 2 diabetes and hypertension in Uygur and Kazak populations.

This study was designed to evaluate the epidemiology of type 2 diabetes and hypertension in Uygur and Kazak ethnic populations. A three-step stratified sampling method was used. Questionnaires, blood pressure, anthropometric measurement, and fasting blood glucose were monitored. In total, 1,571 Uygur and 2,913 Kazak subjects were randomly enrolled. The prevalence of type 2 diabetes and glucose intolerance was 5.55- and 1.90-fold higher, respectively, in Uygur than in the Kazak population (8.16 vs. 1.47%, P < 0.001 and 3.29 vs. 1.73%, P < 0.001). However, the prevalence of hypertension and obesity was significantly higher in the Kazak than in the Uygur population (hypertension: 43.52 vs. 31.98%, P < 0.001; obesity: 25.0 vs. 14.5%, P < 0.001, respectively). Our data suggest a significantly different prevalence in hypertension, hyperlipidemia, and type 2 diabetes between the two ethnic groups. The prevalence of type 2 diabetes was much lower, while the prevalence of hypertension was much higher associated with a higher incidence of obesity in the Kazak population. Individuals with a greater BMI and blood pressure were more prone to development of type 2 diabetes. Our data revealed that waist circumference of Kazak ethnics was greater than that of Uygur, even at the same BMI level. Serum fasting glucose was associated with different factors in Uygur and Kazak.