Screening of Phyllanthus niruri Leaves Phytoconstituents for Antiviral and Antibacterial Activity by Molecular Docking Studies.

The genus Phyllanthus belongs to one of the largest plant families, the Phyllantaceae (L.). Phyllanthus niruri is an annual perennial herb that grows in tropical Asia, America, China, and the islands of the Indian Ocean. Numerous alkaloids, steroids, flavonoids, lignans, coumarins, polyphenols, and lipids are present in Phyllanthus. The effects of plants have been studied for a variety of purposes, including their antioxidant (Giribabu et al., Evid Based Complement Alternat Med, 2014), anti-inflammatory (Porto et al., Revista Brasileira de Pharmacognosy, 2013), antinociceptive (Sathisha et al., Indian Drugs, 2009), analgesic (Mostofa et al., BMC Complement Altern Med, 2017), antiulcer (Mali et al., Biomed Aging Pathol, 2011), antiarthritic (Obidike and Salawu, Planta Medica, 2010), antiplasmodial (Shilpa et al., Environ Dis, 2018), immunomodulatory (Manikkoth et al., Anticonvulsant activity of Phyllanthus amarus in experimental animal models), anticonvulsant (Wasnik et al., Int J Pharm Sci Rev Res, 2014), antidepressant (Venkateswaran et al., Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: In vitro and in vivo studies (antiviral agent/Marmota monax/DNA polymerase/hepatitis B surface antigen/woodchuck hepatitis surface antigen). In Hepatitis B and The Prevention of Primary Cancer of The Liver: Selected Publications of Baruch S Blumberg, pp 535-539), antiviral (Venkateswaran et al., Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: In vitro and in vivo studies (antiviral agent/Marmota monax/DNA polymerase/hepatitis B surface antigen/woodchuck hepatitis surface antigen). In Hepatitis B and The Prevention of Primary Cancer of The Liver: Selected Publications of Baruch S Blumberg, pp 535-539), antitumor (Sharma et al., Asian Pac J Cancer Prev, 2009), hyperlipidemia (Khanna et al., J Ethnopharmacol, 2002), and antifertility (Ezeonwu, Inquiries J, 2011). For additional docking investigations with distinct proteins, the leaf chemicals are assessed, that is, the crystal structure of serine protease hepsin in complex with inhibitor [PDB ID:5 CE1] for antiviral activity human topoisomerase II beta in complex with DNA and etoposide [PDB ID:3QX3] and crystal structure of E. coli GyraseB 24 kDa in complex with 4-(4-bromo-1H-pyrazol-1-yl)-6-[(ethylcarbamoyl)amino]-N-(pyridin-3-yl) pyridine-3-carboxamide [PDB ID: 6F86] for antibacterial activity and have been selected. To evaluate the in silico results and grading of virtual screening, or molecular docking, ritonavir antiviral activity and ampicillin for antibacterial activity were used as a benchmark.

Utilization of genetic testing in men with advanced prostate cancer.

BACKGROUND: Genetic evaluation of men with advanced prostate cancer is recognized as imperative both to guide treatment decisions and to trigger cascade genetic testing of family members. Here we investigate utilization patterns of genetic testing among a contemporary cohort of men with advanced prostate cancer at our institution. METHODS: We queried the Northwestern Electronic Data Warehouse from January 2021 to present for all men diagnosed with National Comprehensive Cancer Network high-risk/very high-risk, regional, or metastatic prostate cancer. Patients were excluded from analyses if treated at an outside institution and/or presented for a second opinion evaluation. Statistics were performed using t-test, Chi-squared test, and univariable and multivariable logistic regression with significance defined as p < 0.05. RESULTS: Atotal of 320 men (52.5%) had local/regional disease and 290 (47.5%) had metastatic disease, 53 (18.3%) of whom had castrate resistant prostate cancer. Rates of germline genetic testing rate were low in patients with localized disease (9.4%) and metastatic disease (34.1%). Only 19 (35.8%) men diagnosed with metastatic castrate resistant prostate cancer underwent germline genetic evaluation. Germline testing was most frequently discussed or ordered by medical oncologists (52%) followed by urologists (20%). Men who underwent germline testing were younger (p < 0.001), more likely to have Medicaid or private insurance (p = 0.002), and more likely to have metastatic disease (p < 0.001). There were no statistically significant differences in baseline PSA, ethnicity, race, or castration sensitivity status. Age (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.91-0.97, p < 0.001) and metastatic disease (OR: 5.71, 95% CI: 3.63-9.22, p < 0.001) were significant independent predictors of genetic testing on multivariable logistic regression. CONCLUSIONS: Here we report that utilization of genetic testing is associated with metastatic disease and inversely associated with age. Overall, utilization rates of genetic testing remain low in all patient groups, including in the metastatic castrate resistant setting, where genetic testing can identify patients with homologous recombination repair deficiency who may benefit from use of targeted therapeutics such as PARP inhibitors. Genetic testing in men with aggressive prostate cancer is critical and barriers to routine implementation of testing require further study to develop strategies to improve utilization rates.

Assessing the Accuracy, Quality, and Readability of Information Related to the Surgical Management of Benign Prostatic Hyperplasia.

Objectives: To assess the accuracy, quality, and readability of online educational health information in English related to the most common benign prostatic hyperplasia (BPH) guideline-approved surgical treatments. Methods: The terms "benign prostatic hyperplasia," "BPH," and all eight guideline-approved treatment modalities studied, were searched to retrieve the first five relevant websites and first two paid advertised websites related to the surgical treatment options for BPH. These modalities included transurethral resection of the prostate (TURP), GreenLight photovaporization, endoscopic enucleation of the prostate, Rezum, Urolift, Aquablation, open simple prostatectomy, and robotic simple prostatectomy (RSP). All relevant websites were assessed for their accuracy, quality, and readability using standardized scoring systems. Results: The mean accuracy score for each of the treatment modalities were all indicative of good accuracy, with 76%-99% of the information presented as being accurate. The median quality score was statistically different across the eight treatment modalities (p = 0.015). The median readability grade level was statistically different across the eight treatment modalities (p = 0.009). Websites that described TURP (median readability grade level, 9.00 [interquartile range (IQR) 8.00-10.80]) were significantly easier to read than those related to RSP (median readability grade level, 14.35 [IQR, 11.08-16.50]) (p = 0.011). No other statistically significant differences were found within the other treatment modality websites. Conclusions: The majority of websites retrieved were found to be of high accuracy, good quality, and poor readability. Additionally, it was found that none of the retrieved websites included descriptions for all the other included treatment modalities. Given these findings, the authors recommend the development of centralized resources with all guideline-approved treatment modalities and accurate, readable, and high-quality information related to the surgical treatment of BPH.

What Is New with Rezum Water Vapor Thermal Therapy for LUTS/BPH?

PURPOSE OF REVIEW: Rezum® is a novel convection-based thermal therapy for benign prostatic hyperplasia (BPH) induced lower urinary tract symptoms (LUTS). This review provides an overview of its safety, efficacy, cost, and potential role in the paradigm of BPH/LUTS therapies. RECENT FINDINGS: Data regarding Rezum® stems primarily from one large randomized controlled trial of 197 patients with 4 years of follow-up. The efficacy and safety of Rezum® is further supported by 4 additional studies including 1 prospective pilot study, 1 crossover study, and 2 retrospective studies. Durable improvements in IPSS (47-60%), QoL (38-52%), Qmax (45-72%), and PVR (11-38%) were seen without causing deterioration of sexual function. Rezum® offers a cost-effective and safe approach to treating BPH/LUTS and should be considered as a possible first-line therapy for patients with moderate to severe symptoms.

Green-Synthesized FeSO4 Nanoparticles Exhibit Antibacterial and Cytotoxic Activity by DNA Degradation.

OBJECTIVE: The current study reports a green, rapid and one-pot synthesis of FeSO4 nanoparticles using Hibiscus rosasinensis floral extract as a reducing and capping agent. 0.5M of FeSO4 was stirred with the floral extract of H. rosasinensis for around 20 minutes at 37ºC and pH 7. METHODS: The development of pink color was considered as the endpoint of reduction and the nanoparticles were characterized by UV-Vis spectrum, EDAX, DLS, FTIR, FESEM, and XRD. UV-Vis spectral analysis indicated a peak at 530 nm and EDAX measurement revealed the presence of Fe, S, O and C elements in the nanoparticle sample. The FTIR analysis showed amines, alcohol and alkene groups that act as capping agents for the produced nanoparticles. FESEM and XRD determination presented FeSO4 nanoparticles of 40-60 nm in size. The synthesized nanoparticles were found to have antibacterial activity against 6 pathogenic bacteria with MIC and MBC of 40 mg/mL. RESULTS: To determine the toxicity at the eukaryotic level, brine shrimp toxicity assay was conducted and 100% mortality was found at concentrations >0.06 mg/mL. Gel shift assay suggested the mechanism of toxicity of FeSO4 NPs by binding and degradation of DNA molecules. CONCLUSION: From the results, the authors demonstrate the ease of green synthesis of FeSO4 nanoparticles and its bioactivity that may have potential applications as drugs and drug delivery systems against various diseases.

Robot-assisted modifications of gait in healthy individuals.

This study investigated whether short-term modifications of gait could be induced in healthy adults and whether a combination of kinetic (a compliant force resisting deviation of the foot from the prescribed footpath) and visual guidance was superior to either kinetic guidance or visual guidance alone in producing this modification. Thirty-nine healthy adults, 20-33 years old, were randomly assigned to the three groups receiving six 10-min blocks of treadmill training requiring them to modify their footpath to match a scaled-down path. Changes of the footpath, specific joint events and joint moments were analyzed. Persons receiving combined kinetic and visual guidance showed larger modifications of their gait patterns that were maintained longer, persisting up to 2 h after intervening over-ground activities, than did persons receiving training with primarily kinetic guidance or with visual guidance alone. The results emphasize the short-term plasticity of locomotor circuits and provide a possible basis for persons learning to achieve more functional gait patterns following a stroke or other neurological disorders.

Gait training after stroke: a pilot study combining a gravity-balanced orthosis, functional electrical stimulation, and visual feedback.

RATIONALE: This case report describes the application of a novel gait retraining approach to an individual with poststroke hemiparesis. The rehabilitation protocol combined a specially designed leg orthosis (the gravity-balanced orthosis), treadmill walking, and functional electrical stimulation to the ankle muscles with the application of motor learning principles. CASE: The participant was a 58-year-old man who had a stroke more than three years before the intervention. He underwent gait retraining over a period of five weeks for a total of 15 sessions during which the gravity compensation provided by the gravity-balanced orthosis and visual feedback about walking performance was gradually reduced. OUTCOMES: At the end of five weeks, he decreased the time required to complete the Timed Up and Go test; his gait speed increased during overground walking; gait was more symmetrical; stride length, hip and knee joint excursions on the affected side increased. Except for gait symmetry, all other improvements were maintained one month post-intervention. CONCLUSIONS: This case report describes possible advantages of judiciously combining different treatment techniques in improving the gait of chronic stroke survivors. Further studies are planned to evaluate the effectiveness of different components of this training in both the subacute and chronic stages of stroke recovery.

Prevention of the down-regulation of gap junctional intercellular communication by green tea in the liver of mice fed pentachlorophenol.

Much evidence has been documented supporting the hypothesis that the down-regulation of gap junctional intercellular communication (GJIC) is a cellular event underlying the tumor promotion process and that treatment to prevent the down-regulation or to up-regulate GJIC is important in preventing tumor promotion. We explored the potential preventive effects of green tea against the promoting action of pentachlorophenol (PCP) in mouse hepatocarcinogenesis, examining whether drinking green tea prevents the down-regulation of GJIC inhibition in the liver caused by tumorigenic doses of PCP. We used a modified in vivo GJIC assay, the incision loading/dye transfer method. Male B6C3F1 mice were given a green tea infusion for 1 week and then PCP was fed at a dose of 300 or 600 p.p.m. in the diet for the following 2 weeks, along with green tea treatment. A dose-related inhibition of GJIC in the hepatocytes was evident in the mice treated with PCP alone that was associated with a reduction in connexin32 (Cx32) plaques in the plasma membrane and an increase in the cell proliferation index. Drinking green tea significantly protected mice against GJIC inhibition, the reduction in Cx32 and the elevation of the labeling index. These findings suggest that green tea might act as an anti-promoter against PCP-induced mouse hepatocarcinogenesis via its ability to prevent down-regulation of GJIC.

Protective effects of green tea on hepatotoxicity, oxidative DNA damage and cell proliferation in the rat liver induced by repeated oral administration of 2-nitropropane.

To evaluate the benefit of green tea in mitigating hazards caused by repeated exposure of 2-nitropropane (2NP), we examined the effects of the tea on toxic indices, oxidative DNA damage and cell proliferation in the liver of 2NP-treated rats. Male Fischer 344 rats were administered, by gastric intubation, a total of six doses of 60 mg/kg 2NP(L), or alternatively two doses of 90 mg/kg and then four doses of 120 mg/kg 2NP(H) during 2 weeks. Green tea infusion was given to the rats as drinking water 1 week before the 2NP treatments and throughout the experiment. Significant elevation of hepatotoxic indices was evident in the 2NP(H)-treated group, such as an increase of serum glutamic-oxaloacetic transaminase (GOT) activity and of hepatic lipid peroxidation, together with a decrease in hepatic glycogen and serum triglyceride, and degenerative changes in the hepatocytes. A dose-related increase was observed in oxidative DNA damage and cell proliferation in the liver. Green tea effectively inhibited all of above changes induced by 2NP treatment, suggesting that tea intake may be effective for preventing the hepatic injuries after chronic exposure to 2NP.

[Inhibitory effect of green tea infusion of hepatotoxicity].

We first showed a drinking of green tea infusion can inhibit chemically induced possible hepatic tissue damages in animal experiments, although it has been shown that oral administration of green tea extract can inhibit some organ toxicities. In this review, our data are summarized and a possibility of the effectiveness in humans is discussed. Male rats or mice in the series of experiments were given 2% green tea infusion as a drinking water 1 or 2 weeks before the chemical treatment and until the termination. In the study of rats, green tea effectively inhibited the hepatotoxicity induced by a single intraperitoneal injection or by repeated gavage administration of 2-nitropropane, and a single intraperitoneal injection of galactosamine. However, any possible effects were not observed when green tea was given, on the hepatotoxicity by a single or repeated gavage administration of carbon tetrachloride. In the study of mice, green tea inhibited the hepatotoxicity induced by administration of pentachlorophenol in diet. In conclusion, 2% green tea infusion can prevent the hepatotoxicity by at least some chemicals in experimental animals. It is inferred that the amount of green tea taken by animals in this experiment might be equivalent to the daily intake in Japanese general population, by calculation based on the content of epigallocatechin gallate, a major component of green tea, and the species differences between experimental animals and humans, suggesting the preventive effectiveness in humans.

Induction of 8-hydroxydeoxyguanosine but not initiation of carcinogenesis by redox enzyme modulations with or without menadione in rat liver.

Inducibility of oxidative stress in rat liver in vivo by menadione-associated redox cycling activation under redox enzyme modulating conditions was examined by monitoring hepatocyte injury and 8-hydroxydeoxyguanosine (8-OHdG) levels of liver DNA. In addition, the treatment-associated liver tumor initiating activity was assessed in terms of development of gamma-glutamyl-transpeptidase (GGT)- and glutathione S-transferase placental form (GST-P)-positive foci and hyperplastic nodules. With or without following menadione treatment (50 mg/kg, i.g.), redox enzyme modulations of increased cytochrome P450 reductase activity induced by phenobarbital (PB)-Na (100 mg/kg, i.p. for 5 days), inhibition of DT-diaphorase by dicumarol (25 mg/kg, i.p.) and depletion of glutathione by phorone (200 mg/kg, i.p.), with or without further supplement of iron EDTA-Na-Fe(III) (70 mg/kg, i.p.), caused both substantial hepatocyte necrosis and 8-OHdG production in Fischer 344 male rats. Subsequent feeding with a 0.05% PB diet for 64 weeks resulted in slightly increased development of GGT-positive foci but not GST-P positive lesions or hyperplastic nodules, suggesting a lack of tumor-initiating activity of the oxidative DNA damage associated with redox enzyme modulations with or without menadione.