Genome-wide identification and functional characterization of borneol dehydrogenases in Wurfbainia villosa.

MAIN CONCLUSION: Genome-wide screening of short-chain dehydrogenases/reductases (SDR) family reveals functional diversification of borneol dehydrogenase (BDH) in Wurfbainia villosa. Wurfbainia villosa is an important medicinal plant, the fruits of which accumulate abundant terpenoids, especially bornane-type including borneol and camphor. The borneol dehydrogenase (BDH) responsible for the conversion of borneol to camphor in W. villosa remains unknown. BDH is one member of short-chain dehydrogenases/reductases (SDR) family. Here, a total of 115 classical WvSDR genes were identified through genome-wide screening. These WvSDRs were unevenly distributed on different chromosomes. Seven candidate WvBDHs based on phylogenetic analysis and expression levels were selected for cloning. Of them, four BDHs can catalyze different configurations of borneol and other monoterpene alcohol substrates to generate the corresponding oxidized products. WvBDH1 and WvBDH2, preferred (+)-borneol to (-)-borneol, producing the predominant ( +)-camphor. WvBDH3 yielded approximate equivalent amount of (+)-camphor and (-)-camphor, in contrast, WvBDH4 generated exclusively (+)-camphor. The metabolic profiles of the seeds showed that the borneol and camphor present were in the dextrorotatory configuration. Enzyme kinetics and expression pattern in different tissues suggested WvBDH2 might be involved in the biosynthesis of camphor in W. villosa. All results will increase the understanding of functional diversity of BDHs.

Can the Sandwich Method Be an Alternative Treatment Choice for BPH Patients With Large Prostates?

OBJECTIVE: To compare the efficacy and safety of the sandwich method with GreenLight photoselective vaporization (GLPVP) and bipolar transurethral resection (B-TURP) with those of the enucleation method in patients with BPH and a prostate volume ≥ 80 g. METHODS: Patients with BPH who underwent either the sandwich method with GLPVP and B-TURP or the enucleation method between 2014 and 2021 were included in the analysis. The primary outcome was the comparison of uroflowmetry results between the 2 groups. Safety analysis of the complication rates was also compared. RESULTS: The cohort included 55 patients in the sandwich group and 41 patients in the enucleation group. In the efficacy analysis, both groups showed comparable uroflowmetry results, except for a higher postoperative average flow rate in the enucleation group. Regarding perioperative parameters, the sandwich method required a longer operating time, and the enucleation group had a higher incidence of manual Foley irrigation. Both groups demonstrated similar postoperative complications. CONCLUSION: The sandwich method exhibited comparable efficacy and safety to the enucleation method in patients with BPH with a prostate volume ≥ 80 g. Thus, for surgeons who are familiar with GLPVP and B-TURP, the sandwich method may be an alternative surgical approach for BPH patients with large prostates.

Anterior fibromuscular stroma-preserved endoscopic enucleation of the prostate: a precision anatomical approach.

BACKGROUND: Benign prostate obstruction (BOO) is becoming increasingly important in this aging society. Some urge/stress urinary incontinence (UUI/SUI) still occurs after endoscopic enucleation of the prostate (EEP). It remains unclear how post-EEP incontinence can be avoided. Currently, early apical release to ameliorate the traction of the external sphincter is the best technique for incontinence prevention. OBJECTIVE: To describe our surgical technique of anterior fibromuscular stroma (AFS)-preserved EEP for BOO. DESIGN, SETTING, AND PARTICIPANTS: The medical records of 60 consecutive patients who underwent AFS-preserved EEP for BOO in our center from September 2019 to December 2019 were retrospectively reviewed. SURGICAL PROCEDURE: AFS-preserved EEP starts at the 12 o'clock position of the urethra, and the junction between the AFS and transitional zone (T-zone) was identified. The AFS and T-zone were separated first to protect the AFS in the initial operative procedure. Then, following the usual enucleation procedure, AFS-preserved EEP could be achieved. MEASUREMENTS: Postoperative prostate-specific antigen (PSA), testosterone, urethral stricture, and voiding status, such as incontinence, uroflow, and postvoiding residual urine were assessed. RESULTS AND LIMITATIONS: The data show that AFS-preserved EEP could achieve similar surgical outcomes as other early apical release approaches. CONCLUSIONS: The preserved AFS provides a nice landmark at the 12 o'clock position during EEP.

Mendelian randomization investigation highlights different roles of selenium status in mental disorders.

Observational studies have suggested a relationship between selenium status and mental disorders (MDs). However, it remains unclear whether selenium status was causally associated with MDs. Thus, we performed a two-sample Mendelian randomization analysis using genome-wide association studies (GWAS) summary statistics to investigate the causal effects of selenium levels on seven MDs, including schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), bipolar disorder (BD), anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), and panic disorder (PD). Strong genetic instruments of blood selenium (n = 9) and blood-toenail selenium (n = 12) were applied to the above seven MDs GWAS datasets from Psychiatric Genomics Consortium, which were further replicated in the FinnGen Biobank. The inverse-variance weighted method was employed to calculate the causal effects. The results showed that genetically predicted blood selenium levels were associated with a decreased risk of schizophrenia (odds ratio [OR] = 0.90, 95% CI: 0.87-0.95) and AN (OR = 0.87, 95% CI: 0.77-0.97). However, both blood and blood-toenail selenium levels were linked to an increased risk of MDD (blood: OR = 1.08, 95% CI: 1.05-1.12; blood-toenail: OR = 1.08, 95% CI: 1.04-1.13) and ASD (blood: OR = 1.11, 95% CI: 1.05-1.17; blood-toenail: OR = 1.13, 95% CI: 1.05-1.21), respectively. No obvious associations were found between selenium levels and BD as well as ADHD. Our findings highlighted a protective role of selenium in SZ and AN, while a risk effect in MDD and ASD. Further studies are required to verify the underlying mechanism mediating the unequal effects of Se on different MDs, which will pave a new path for the intervention of MDs.

Safety assessment of oil extracted from lacquer (Toxicodendron vernicifluum (Stokes) F.A. Barkley) seed: acute and subchronic toxicity studies in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Toxicodendron vernicifluum (Stokes) F.A. Barkley (RVS) is an economic tree species and widely distributed in East Asia. Wood parts and raw lacquers of RVS have been used in coatings, herbal medicines or food supplements, and the leaves, flowers, roots, and fruits of RVS are also widely used in medicine traditionally. Lacquer seed oil (LSO) has potential health benefits and has not previously been evaluated for safety. AIM OF THE STUDY: The aim of the present study was to investigate the toxicological potential of LSO by acute and subchronic toxicity tests. MATERIALS AND METHODS: The characterization of fatty acids of the LSO was carried out by gas chromatography. In the acute toxicity study, LSO was administered at single doses of 5000 or 10000 mg/kg by oral gavage. The subchronic toxicity study was conducted by daily oral administration of LSO at doses of 1250, 2500 and 5000 mg/kg/day for 30 consecutive days. The animals were evaluated for clinical observations, body weight, organ weight, feed consumption, biochemical and hematological parameters, and liver, lung, and kidney histology. RESULTS: There were no mortality and toxic changes were observed in acute toxicity study. The results of subchronic toxicity showed no toxicologically significant changes in clinical observations, body weight, organ weight, biochemical or hematological parameters. Histopathologic results indicated slight hepatic steatosis and inflammatory infiltration in the rats of 5000 mg/kg/day LSO treated group. However, the histopathologic observation was not confirmed by hepatic biochemical analysis. CONCLUSIONS: These results suggested that the LD50 of LSO is over 10000 mg/kg and LSO is non-toxic for SD rats in acute toxicity study. The no observed adverse effect level (NOAEL) of LSO in rats is considered to be 5000 mg/kg/day, and liver is the potential target organ of LSO for 30-day subchronic toxicity study.

Protective action of pomegranate peel polyphenols in type 2 diabetic rats via the translocation of Nrf2 and FoxO1 regulated by the PI3K/Akt pathway.

The aim of this study is to investigate the protective mechanism of pomegranate peel polyphenols (PPPs) in in vivo and in vitro rat models of T2DM. Our results showed that PPPs markedly improved the symptoms of diabetes, such as insulin resistance, impaired insulin secretion, and pancreatic oxidative damage, which contributed to the attenuation of the symptoms of hyperglycemia in a high-fat diet (HFD) combined with streptozocin (STZ) induced type 2 diabetes mellitus in rats. On the one hand, PPPs promoted the translocation of Nrf2 from the cytoplasm to the nucleus, the key protein down-regulated by the PI3K/Akt pathway, activating its downstream phase 2 antioxidant enzyme system. On the other hand, the positive effect was associated with another downstream protein of the PI3K/Akt pathway, FoxO1. With the activation of Akt phosphorylation, the phosphorylated FoxO1 protein transferred from the nucleus to the cytoplasm, releasing the block of Pdx-1 and its downstream genes. The inhibitor of the PI3K/Akt pathway was also studied in INS-1 cells in order to verify the mechanism observed in vivo. Altogether, we presented evidence that PPPs activated the translocation of Nrf2 into the nucleus and resulted in increased antioxidant activity, and PPPs promoted the translocation of FoxO1 out of the nucleus resulting in an increase in insulin synthesis in vivo and in vitro. Pomegranate extracts may show great potential and application prospects as functional foods or preventive drugs to improve pancreatic beta cell dysfunction and provide a reference for future development in health care.

Revealing the developmental dynamics in male strobilus transcriptome of Gnetum luofuense using nanopore sequencing technology.

Gnetum is a pantropical distributed gymnosperm genus. As being dioecious, Gnetum species apply female and male strobili to attract and provide nutrition to insect pollinators. Due to its unique gross morphology, a Gnetum male strobilus receives much attention in previous taxonomic and evolutionary studies. However, underlying molecular mechanisms that control male strobilus development and pollination adaptation have not been well studied. In the present study, nine full-length transcriptomes were sequenced from three developmental stages of the G. luofuense male strobili using Oxford Nanopore Technologies. In addition, weighted gene co-expression network analysis (WGCNA), and RT-qPCR analysis were performed. Our results show that a total of 3138 transcription factors and 466 long non-coding RNAs (lncRNAs) were identified, and differentially expressed lncRNAs and TFs reveal a dynamic pattern during the male strobilus development. Our results show that MADS-box and Aux/IAA TFs were differentially expressed at the three developmental stages, suggesting their important roles in the regulation of male strobilus development of G. luofuense. Results of WGCNA analysis and annotation of differentially expressed transcripts corroborate that the male strobilus development of G. luofuense is closely linked to plant hormone changes, photosynthesis, pollination drop secretion and reproductive organ defense. Our results provide a valuable resource for understanding the molecular mechanisms that drive organ evolution and pollination biology in Gnetum.

[Communication in process of R&D and registration of new drugs of traditional Chinese medicine].

In recent years, the National Medical Products Administration has established a communication system for the process of drug R&D and registration. In this paper, the reform policies on establishing the communication system for drug evaluation in recent years were summarized, and the channels, processes, methods and types of communication were also collected. In addition, the communication status of new drugs of traditional Chinese medicine(TCM) was summarized according to the whole process of R&D, including summary of clinical practice, Investigational New Drug Applications, period of clinical trials, New Drug Applications, and post-marketing researches. Meanwhile, the current problems such as ineffective, inefficient, repeated or even no communication were analyzed, and relevant suggestions were proposed accordingly in order to provide reference for better communication on R&D and registration of new drugs of TCM.

Clinical outcome of transurethral enucleation of the prostate using the 120-W thulium Laser (Vela™ XL) compared to bipolar transurethral resection of the prostate (TURP) in aging male.

This study compared the surgical outcomes of the 120-W Thulium laser (Vela™ XL) enucleation of the prostate and bipolar transurethral resection of the prostate (TURP) in terms of efficacy, safety, and improvements of quality of life (QoL) in patients with benign prostate hyperplasia (BPH). Records were obtained from January 2014 to September 2018 for selected patients with symptomatic BPH who underwent 120-W Thulium laser (Vela™XL) prostate enucleation and bipolar TURP in our institution. All the patients selected met the surgical criteria for TURP and had received medical treatment for at least 3 months. Patients were excluded if their ECOG performance status was >1, if they had active malignant disease, of if they had a history of prostate surgery or reconstruction surgery of the urinary system. Patients decided which treatment option would be performed. Both the procedures were conducted by a single surgeon. Clinical outcomes such as changes in the International Prostate Symptom Score (IPSS) score, urodynamic parameters, drug consumption, pain scores, and QoL were evaluated. The rate of urinary tract infection, recatheterization, additional analgesic requirement, return to the emergency department for treatment, and other surgical complications was analyzed and compared between the two cohorts. A total of 276 patients met the inclusion criteria. Among them, 141 patients received bipolar TURP, where as 135 decided to receive laser vaporesection. No significant difference was observed in age, PSA level, prostate volume, and comorbidities between the two cohorts. Pre-operative (pre-op) urodynamic parameters were also identical, except that the laser surgery group had a higher rate of admission with a urinary catheter (24.4% vs. 14.2%, p=0.044). The operating time was longer in the laser surgery group (79.3 minutes vs. 62.4 minutes, p<0.001). However, enucleation using the Thulium laser was superior to bipolar TURP in terms of post-operative (post-op) pain status, including the numeric rating scale of pain, rate of additional narcotic use, and oral analgesic requirement. Compared with bipolar TURP, laser enucleation achieved a higher improvement in the QoL score at post-op follow-up at 2 weeks and 3 months. Nevertheless, the complication rate, changes in IPSS score, Qmax, and post-op medication-free survival were statistically identical in the two cohorts. Our data revealed that compared with bipolar TURP, 120-W Thulium laser (Vela™ XL) enucleation of the prostate achieved lower post-op pain and higher improvement in the short-term QoL of patients after surgery.

Pomegranate peel polyphenols reduce chronic low-grade inflammatory responses by modulating gut microbiota and decreasing colonic tissue damage in rats fed a high-fat diet.

Recent studies have found that a high-fat diet (HFD) causes gut microbiota imbalance and colon tissue damage, resulting in increased intestinal permeability, which is one of the main reasons for the existence of constantly circulating low-grade inflammatory cytokines. Pomegranate extracts have been shown to protect from HFD-induced metabolic inflammation (e.g., colitis) and to promote the growth of beneficial bacteria in in vitro stool cultures. However, whether the beneficial effects of pomegranate extracts on the HFD-induced metabolic inflammation are achieved by acting on intestinal tissues has not yet been studied. In our present study, we found that pomegranate peel polyphenols (PPPs) alleviated HFD-induced obesity, elevated circulating pro-inflammatory cytokines, colonic tissue damage, and depressed colonic tight junction protein expression level in rats. Moreover, PPPs normalized the HFD-induced gut microbiota imbalance by increasing the abundance of beneficial bacteria in the colon. Furthermore, we also found that PPPs, punicalagin, and urolithin A (the main microbiota metabolites of pomegranate ellagitannins) all increased the LPS-induced decreased tight junction protein expression level and reversed the LPS-induced inflammatory response in Caco-2 cells. Urolithin A exhibited the best effects among the three pomegranate components. Our results suggested that the protective effects of PPPs in HFD-induced metabolic inflammation can be due to the recovery of colonic tissue damage and the regulation of gut microbiota and that urolithin A is the major component that contributes to the in vivo effects of PPPs.

Beneficial Effects of Pomegranate on Lipid Metabolism in Metabolic Disorders.

Pomegranate (Punica granatum Linn) is used in the prevention and treatment of metabolic syndrome in recent decades. Imbalances in lipid metabolism are profound features of metabolic disorders. In vivo and in vitro studies have shown that extracts of different pomegranate fractions (peels, flowers, juice, and seeds) regulate lipid metabolism in metabolic-disorder-associated diseases such as atherosclerosis, nonalcoholic fatty liver disease, and type 2 diabetes, helping to alleviate the development of diseases. Amelioration of oxidative stress and the inflammatory response is considered an important reason underlying the regulation of lipid metabolism by pomegranate extracts. Mitochondria, the major cellular site for lipid oxidation, are strongly associated with cellular oxidative and inflammatory status and are likely to be a target for pomegranate extract action. This review summarizes the main findings about the effects of different pomegranate fraction extracts on lipid metabolism in metabolic-disorder-associated diseases and analyses how pomegranate extracts achieve their effects. Furthermore, it also provides an important basis for the research and development of pomegranate-related nutrients or drugs.

Multi-layered tumor-targeting photothermal-doxorubicin releasing nanotubes eradicate tumors in vivo with negligible systemic toxicity.

Multi-layered single-walled carbon nanotubes, termed SWNT@BSA@Au-S-PEG-FA@DOX, which integrate photothermal therapy with small molecule drug delivery, were prepared using a facile layer-by-layer assembly process. Oxidized and cut single-walled carbon nanotubes (SWNTs) were coated with bovine serum albumin (BSA) to provide abundant active sites for the nucleation of Au seeds, which are subsequently converted into gold nanoparticles (Au NPs) by in situ reduction. The resulting SWNT@BSA@Au material exhibits ideal photothermal properties. Further modification of the nanomaterial with folic acid terminated-polyglycol (FA-PEG-SH) and subsequent loading with doxorubicin (DOX) afford the SWNT@BSA@Au-S-PEG-FA@DOX. The FA terminated PEG endows the material with high water-dispersibility, biocompatibility and cancer cell selectivity. A high drug loading ratio for DOX of up to 590% was achieved, with the drug release being pH and temperature dependent, adding to the selectivity of the system. High efficacy of the SWNT@BSA@Au-S-PEG-FA@DOX material, when combined with photothermal therapy (irradiation of the tumor with an 808 nm laser, 1 W cm-2 for 5 min, 24 h after systemic injection of the nanomedicine), was demonstrated in vivo, resulting in complete tumor eradication. Remarkably, the side effects are negligible with only minor damage to normal tissues including the liver and kidneys being observed.

Transurethral resection of the prostate provides more favorable clinical outcomes compared with conservative medical treatment in patients with urinary retention caused by benign prostatic obstruction.

BACKGROUND: To evaluate the long-term surgical outcomes of patients with urinary retention (UR) caused by a benign prostatic obstruction (BPO) who underwent transurethral resection of the prostate (TURP), and compare their outcomes with those of patients who received medication without surgical intervention. METHODS: This retrospective cohort study analyzed claims data collected during the period of 1997-2012 from Taiwan's National Health Insurance Research Database. We examined geriatric adverse events among patients who had received a diagnosis of symptomatic benign prostatic hyperplasia and whom experienced UR, and compared those who received TURP and medication only. Primary outcomes included urinary tract infection (UTI), UR, inguinal hernia, hemorrhoids, stroke, acute myocardial infarction, and bony fracture. We excluded patients who had concomitant prostate cancer, bladder cancer, or a long-term urinary catheter indwelling, as well as those who did not receive α-blocker medication regularly. Those aged <50 or >90 years were also excluded. The enrolled patients were categorized into TURP (n = 1218) and medication only (n = 795) groups. After 1:1 propensity score matching, we recorded and compared patients' characteristics, postoperative clinical outcomes, and geriatric adverse events. RESULTS: The TURP cohort had a lower incidence of UTI and UR during the postoperative follow-up period from 2 months to 3 years than did the medication only group (20.7% vs. 28.9% and 12.5% vs. 27.6%, respectively, p < 0.001). The life-long bone fracture incidence was also lower in the TURP cohort (7.9% vs. 9.2%, p = 0.048). The incidence of other outcomes during the postoperative follow-up period did not differ between the two groups. CONCLUSIONS: Compared with conservative treatment, TURP provides more favorable clinical outcomes in patients with UR caused by BPO. Patients who underwent TURP had a lower risk of UTI, repeat UR episodes, and emergent bony fracture. Thus, early surgical intervention should be considered for such patients.

Transurethral resection of the prostate achieves favorable outcomes in stroke patients with symptomatic benign prostate hyperplasia.

OBJECTIVES: To evaluate the surgical outcomes of stroke patients with symptomatic benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TURP) and compare the clinical outcomes between patients with stroke and those without stroke receiving this procedure. METHODS: This retrospective cohort study analyzed claims data collected during the period of 1997-2012 from Taiwan National Health Insurance Research Database. We enrolled 6625 patients who had persistent lower urinary tract symptoms and underwent TURP for BPH. They were categorized into a stroke (n = 577) and nonstroke (n = 6048) group. Patient characteristics, postoperative clinical outcomes, medication records, and medical expenses were compared. RESULTS: Compared with the stroke group patients, those in the nonstroke group were younger, had fewer comorbidities, and more favorable postoperative clinical outcomes. Nevertheless, TURP achieved favorable outcomes in stroke patients with symptomatic BPH. In the stroke group, the rate of urinary tract infection (UTI) decreased from 34.7% during 1 year preoperatively to 29.8% during 1 year postoperatively (p = .05). The rate of urinary retention (UR) also decreased from 55.5% during 1 year preoperatively to 22.5% during 1 year postoperatively (p = .05). TURP reduced the overall medical expenses of patients with stroke. Annual patient medical expense during 1 year preoperatively, 1 year postoperatively, 2 years postoperatively, and 3 years postoperatively was NT$659,000, NT$646,000, NT$560,000, and NT$599,000, respectively. CONCLUSIONS: In patients with stroke, TURP reduces the risks of UTI and UR and annual total medical expense.

Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O2-exposed newborn rat.

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFß1 activation.

Is diabetes mellitus associated with clinical outcomes in aging males treated with transurethral resection of prostate for bladder outlet obstruction: implications from Taiwan Nationwide Population-Based Cohort Study.

PURPOSE: We assessed the lower urinary tract symptoms (LUTSs) and clinical outcomes between diabetes mellitus (DM) patients and non-diabetic (non-DM) patients receiving transurethral resection of prostate (TUR-P). METHODS: This analysis was a retrospective cohort study using 13 years (2000-2012) of claims data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 4,887 patients who had persistent LUTSs and underwent TUR-P for prostate enlargement (benign prostate enlargement [BPE]) were enrolled and divided into two groups: DM and non-DM groups. The patients' characteristics, postoperative clinical outcomes, and the medication records after TUR-P were compared. Chi-square test was used for categorical variables and independent samples t-test for continuous variables. Multivariable logistic regression analysis was used to compare the risk of postoperative outcomes. Finally, we estimated the medication-free survival rate after TUR-P using Kaplan-Meier method and compared it between study groups using log-rank test. RESULTS: DM group patients had a higher prevalence of comorbidities. Postoperatively, the DM group had lower rates of urinary tract infection (UTI; odds ratio [OR], 0.78; P=0.009) and higher rates of urinary retention requiring catheterization (OR, 1.35; P=0.01) within 1 month after TUR-P. A higher proportion of patients with DM took anti-muscarinics (OR, 1.23; P=0.032) within the first 3 months and α-blockers (OR, 1.18; P=0.049) during 3-12 months after receiving TUR-P. Overall, the DM group patients had a worse postoperative medication-free survival compared to that of non-DM group patients (95% confidence interval [95% CI], 1.14; P=0.005). CONCLUSION: DM patients require higher rates of continuing medication after TUR-P, especially anti-muscarinics in 3 months postoperatively and alpha-blocker after 3 months postoperatively. DM patients also had higher incidence of urine retention after surgery. DM patients had relatively poor treatment outcomes compared to DM-free patients.

Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats.

High blood pressure, or "hypertension," is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension.

Genetic Code Expansion by Degeneracy Reprogramming of Arginyl Codons.

The genetic code in most organisms codes for 20 proteinogenic amino acids or translation stop. In order to encode more than 20 amino acids in the coding system, one of stop codons is usually reprogrammed to encode a non-proteinogenic amino acid. Although this approach works, usually only one amino acid is added to the amino acid repertoire. In this study, we incorporated non-proteinogenic amino acids into a protein by using a sense codon. As all the codons are allocated in the universal genetic code, we destroyed all the tRNA(Arg) in a cell-free protein synthesis system by using a tRNA(Arg) -specific tRNase, colicin D. Then by supplementing the system with tRNACCU , the translation system was partially restored. Through this creative destruction, reprogrammable codons were successfully created in the system to encode modified lysines along with the 20 proteinogenic amino acids.

Economic Evaluation Study (Cheer Compliant) Laser Prostatectomy for Benign Prostatic Hyperplasia: Outcomes and Cost-effectiveness.

To determine which surgical treatment for lower urinary tract symptoms, which is suggestive of benign prostatic hyperplasia (BPH), is more cost-effective and yields a better patient's preference. Treatment outcome, cost, and perioperative complications to assess the treatment effectiveness of using laser prostatectomy as a treatment for BPH were investigated in this study.This retrospective study included 100 patients who underwent transurethral resection of prostate (TUR-P) and another 100 patients who received high-powered 120 W (GreenLight HPS) laser prostatectomy between 2005 and 2011.International Prostate Symptom Score and uroflow parameters were collected before the surgery and the uroflow and postvoiding residual volumes were evaluated before treatment and at 3, 6, 12, and 24 months after treatment. The results of 100 treatments after HPS laser prostatectomy were compared with the results of 100 patients who received TUR-P from the same surgeon. Complication rates and admission costs were analyzed.From 2005 to 2011, 200 consecutive patients underwent endoscopic surgery. Study participants were men with BPH with mean age of 71.3 years old. The peak flow rate went from 8.47 to 15.83 mL/s for 3 months after laser prostatectomy. Laser therapy groups showed better improvement in symptom score, shortened length of stay, and quality of life score when compared with those of TUR-P procedures. The estimated cost for laser prostatectomy was high when compared with cost of any other TUR-P procedural option at Chang Gung Hospital (P = 0.001). All admission charges were similar except for the cost of the laser equipment and accessories (mainly the laser fiber) (P = 0.001). Due to this cost of equipment, it increased the total admission charges for the laser group and therefore made the cost for the laser group higher than that of the TUR-P group.Perioperative complications, such as the need for checking for bleeding, urinary retention rate or urosepsis rate within 30 days after the surgery, held no significant differences between both groups.Compared with alternative treatment options, laser prostatectomy of the prostate is clinically effective but yields a high cost of treatment for symptomatic BPH.

Coral calcium hydride prevents hepatic steatosis in high fat diet-induced obese rats: A potent mitochondrial nutrient and phase II enzyme inducer.

Diet-induced nonalcoholic fatty liver disease (NAFLD) is characterized by profound lipid accumulation and associated with an inflammatory response, oxidative stress and hepatic mitochondrial dysfunction. We previously demonstrated that some mitochondrial nutrients effectively ameliorated high fat diet (HFD)-induced hepatic steatosis and metabolic disorders. Molecular hydrogen in hydrogen-rich liquid or inhaling gas, which has been confirmed in scavenging reactive oxygen species and preventing mitochondrial decay, improved metabolic syndrome in patients and animal models. Coral calcium hydride (CCH) is a new solid molecular hydrogen carrier made of coral calcium. However, whether and how CCH impacts HFD-induced hepatic steatosis remains uninvestigated. In the present study, we applied CCH to a HFD-induced NAFLD rat model for 13 weeks. We found that CCH durably generated hydrogen in vivo and in vitro. CCH treatment significantly reduced body weight gain, improved glucose and lipid metabolism and attenuated hepatic steatosis in HFD-induced obese rats with no influence on food and water intake. Moreover, CCH effectively improved HFD-induced hepatic mitochondrial dysfunction, reduced oxidative stress, and activated phase II enzymes. Our results suggest that CCH is an efficient hydrogen-rich agent, which could prevent HFD-induced NAFLD via activating phase II enzymes and improving mitochondrial function.