Levels and health risk assessment of pesticides and metals in Lycium barbarum L. from different sources in Ningxia, China

The berries of Lycium barbarum L. (Goji) are widely used as a Chinese traditional herbal medicine and functional food because of their reported beneficial pharmacological effects. However, there are reports of Goji berries being contaminated by chemical residues that could pose a hazard to humans. In this study, samples of L. barbarum L. berries were collected from plantations in a genuine production area and supermarkets in Ningxia, China. The major hazardous chemicals, including pesticides (dichlorvos, omethoate, cypermethrin, fenvalerate, malathion, and deltamethrin) and metals (lead (Pb), cadmium (Cd), copper (Cu), nickel (Ni), zinc (Zn), and arsenic (As)), were quantified by gas chromatography and inductively coupled plasma-optical emission spectrometry. In addition, associated daily exposures and health risks were determined using deterministic and probabilistic assessments. The levels of five pesticides from the plantation samples were considerably lower than the maximum residue limits; only dichlorvos was detected in the supermarket samples, and deltamethrin was not detected in any samples. Cu, Zn, As, Pb, Ni and Cd were detected in samples from both sources. The hazard quotient values of individual hazardous chemicals and the hazard index of combined hazardous chemicals were considerably less than 1, indicating the absence of a non-carcinogenic effect of hazardous chemical exposures through Goji berry consumption. The R value of As was much less than 10–6, which shows that consumption of the Goji berries had no obvious carcinogenic risks. The potentially harmful effects of the L. barbarum L. are more likely from berries obtained from plantations than those from supermarkets, and metal exposure is more dangerous than pesticide exposure. However, on the basis of our analysis, no population would be exposed hazardous chemicals exceeding existing standards, and the factors most affecting the health risk were exposure frequency and As content.

Safety assessment of a new anti-tuberculosis drug in silico and with the participation of healthy volunteers

Relevance. In connection with the increase in the number of cases of multidrug-resistant tuberculosis (MDR-TB), the search for new anti-tuberculosis drugs (ATD) is necessary. The assessment of its effect on the human body outside the aspect of the therapeutic effect is one of the main directions in the development of anti-TB drugs.Aim. Evaluation of the possible toxicity of thiosonide, a new domestic anti-TB drug, combining a consistent study of this side of the drug using a bioinformatics approach and an analysis of the results of a clinical safety study.Methods. The bioinformatic assessment was carried out using web services and models to predict the toxicity of thiosonide. The safety assessment in relation to healthy volunteers was carried out as part of a clinical study according to the protocol: «An open-label study of the pharmacokinetics, safety and tolerability of the drug thiozonide, capsule 100 mg with a single dose of increasing doses by various groups of healthy volunteers.» (2013, Permit No. 187 to conduct a clinical trial dated March 22, 2013, issued by the Ministry of Health of the Russian Federation).Results. Potential unwanted targets were identified, the predicted activity value for which was greater than 7. The results obtained indicate the likelihood of the effect of thiosonide on these protein targets and, possibly, the ability of the latter to cause side effects associated with changes in the activity of these molecules. The cytotoxic and carcinogenic effect of thiosonide is not predicted. During a clinical study, the drug thiosonide showed good tolerance and safety, since the identified adverse events did not show a definite or reliable relationship with the study drug. The resolution of all adverse events was complete, and dose escalation did not affect the number, severity of AEs and association with the study drug.Conclusion. The safety analysis of thiosonide demonstrated its good tolerability both during in silico assessment and in a study with the participation of healthy volunteers.

Dyshormonal dysplasias of the mammary gland in adolescent girls

436 juvenile girls were examined. The results received indicate that dyshormonal dysplasia of mammary glands takes an important place in gynecologic morbidity of juvenile girls (11% of those who consulted a gynecologist). Diffuse forms that can be treated conservatively are mostly diagnosed. The main diagnostic methods in teenagers are palpation and MESUSS. Considering polyethiology of the disease, conservative therapy ought to be complex. To avoid carcinogenic effect of oral contraceptives, they may be used in case of non-complicated heredity, intact liver, and non-complicated course of perinatal period of the girl.

Lifestyle and Hepatocellular Carcinoma What Is the Evidence and Prevention Recommendations

The increasing burden of hepatocellular carcinoma (HCC) emphasizes the unmet need for primary prevention. Lifestyle measures appear to be important modifiable risk factors for HCC regardless of its etiology. Lifestyle patterns, as a whole and each component separately, are related to HCC risk. Dietary composition is important beyond obesity. Consumption of n-3 polyunsaturated fatty acids, as well as fish and poultry, are inversely associated with HCC, while red meat, saturated fat, and cholesterol are related to increased risk. Sugar consumption is associated with HCC risk, while fiber and vegetable intake is protective. Data from multiple studies clearly show a beneficial effect for physical activity in reducing the risk of HCC. However, the duration, mode and intensity of physical activity needed are yet to be determined. There is evidence that smoking can lead to liver fibrosis and liver cancer and has a synergistic effect with alcohol drinking. On the other hand, an excessive amount of alcohol by itself has been associated with increased risk of HCC directly (carcinogenic effect) or indirectly (liver fibrosis and cirrhosis progression. Large-scale intervention studies testing the effect of comprehensive lifestyle interventions on HCC prevention among diverse cohorts of liver disease patients are greatly warranted.

TEX10 Promotes the Tumorigenesis and Radiotherapy Resistance of Urinary Bladder Carcinoma by Stabilizing XRCC6

Urinary bladder carcinoma refers to the commonest carcinoma with weak prognostic result for the patient as impacted by the limited treatment possibilities and challenging diagnosing process. Nevertheless, the molecular underpinning of bladder carcinoma malignant progression is still not clear. As a novel core part of pluripotency circuitry, testicular expression 10 (TEX10) plays an actively noticeable effect on reprogramming, early embryo development, and embryonic stem cell self-renewal. Nevertheless, TEX10 expressions and functions within bladder carcinoma are still not known. The present work is aimed at revealing TEX10 expression and biological function within urinary bladder carcinoma and elucidating the potential mechanisms. Results showed that TEX10 is abundant in urinary bladder carcinoma, and its protein level was related to poor disease-free survival in a positive manner. Reduced TEX10 level inhibited urinary bladder carcinoma cell proliferating process and metastasis in vitro and xenograft tumorigenicity in vivo. Notably, TEX10 might regulate carcinoma cell proliferating process and metastasis via XRCC6, thereby controlling the signaling of Wnt/β-catenin and DNA repair channel. Moreover, TEX10 gene knockout reduced the radiotherapy resistance of urinary bladder carcinoma. In brief, this work revealed that TEX10 could exert a significant carcinogenic effect on urinary bladder carcinoma tumorigenesis and radiotherapy resistance through the activation of XRCC6-related channels. Accordingly, targeting TEX10 is likely to offer a novel and feasible therapeutically related strategy for inhibiting urinary bladder carcinoma tumorigenicity.

Pan-cancer survey and evaluation of the oncogenic role of NF-κB1

Although emerging cells or animals based evidence supports an association between nuclear factor kappa-B1 (NF-κB1) cells and cancers, there has no pan-cancer analysis. Therefore, based on TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) data sets, we first studied the potential carcinogenic effect of NF-κB1 in 33 tumors. As we not only found high expression of NF-κB1 in most tumors, but also found that NF-κB1 expression is closely related to the prognosis of tumor patients. Enhanced phosphorylation of S893 was observed in several tumors, such as breast cancer, uterine corpus endometrial carcinoma or lung adenocarcinoma. In thymoma, NF-κB1 expression was relevant to CD8+ T-cell infiltration levels, and tumor-associated fibroblast infiltration has also seen in other tumors, such as uterine corpus endometrial carcinoma or glioblastoma multiforme. In addition, the functional mechanism of NF-κB1 also involves the related functions of protein processing and RNA metabolism. In this study, NF-κB1 was pan-cancer study in order to have a systematic and comprehensive understanding of the carcinogenic effect of NF-κB1 in different tumors.

Rasio Penutupan Luka pada Tikus Diabetes Diinduksi Streptozotocin dengan Perlakuan Dressing Tipe Pasif dan Interaktif (Penelitian Pendahuluan)

Deparaffinization is a stage before the staining process to remove/dissolve paraffin so that the absorption of color in tissue preparations is maximized. Deparaffinization is usually carried out using xylol and toluol. Xylol has toxic effects including acute neurotoxicity, heart and kidney damage, hepatotoxicity, fatal blood dyscrasias, skin erythema, dry skin, peeling skin, and also has a carcinogenic effect. The toxicity effect of olive oil is lower than that of xylol. Oils that have non-polar properties can remove the remaining paraffin contained in the tissue. The purpose of this study was to determine the microscopic appearance of the kidney tissue preparations of mice deparaffinized with olive oil on hematoxylin eosin (HE) staining. The type of research used is experimental research which is analyzed with a descriptive approach. The results of the assessment of preparations deparaffinized with xylol in 80 visual fields obtained 100% good preparations and preparations deparaffinized with olive oil in 80 visual fields obtained 0% poor preparations, 11.3% poor preparations, and 88.7% good preparation. So it can be said that better results are found in the microscopic picture of the kidney preparations of mice (Mus musculus) deparaffinized with xylol.

MiR-20a-5p Negatively Regulates NR4A3 to Promote Metastasis in Bladder Cancer

Metastasis is the leading cause of death in cancer patients. Therefore, the prediction and treatment of metastasis are critical in improving the survival of patients with bladder cancer. In this study, we aimed to investigate the role of miR-20a-5p and NR4A3 in bladder cancer and the regulatory relationship between them. The high expression of miR-20a-5p in the bladder cancer (BCa) tissues and cells was determined by qRT-PCR. Exogenous miR-20a-5p overexpression promoted the proliferation, migration, and invasion of BCa cells. MiR-20a-5p inhibition inhibited the BCa cell proliferation, invasion, and migration. NR4A3 was proved to be the target gene of miR-20a-5p by the double luciferase reporter assay. In addition, the reduction of NR4A3 could promote the proliferation, invasion, and clonal formation of the bladder cancer cells 5637 and T24. NR4A3 overexpression could reverse the carcinogenic effect of miR-20a. We further confirmed that the oncogenic effect of miR-20a was achieved by promoting EMT in tumor cells. MiR-20a-5p promoted the growth and metastasis of the bladder cancer cells by inhibiting the expression of the tumor suppressor gene NR4A3 and played a carcinogenic role in BCa. Thus, miR-20a-5p may become a potential therapeutic target for BCa treatment.

A critical Review of Dhoopan Karma in Ayurveda and Dhoopana of an Ayurvedic Herbomineral formulation Yavasarshapadi churna in context of Sterilization.

Dhoopana Karma is classical remedy mentioned in various Ayurvedic scriptures to maintain disease free and hygienic environment in the world. As per Ayurvedic scriptures Dhoopana is indicated for Rakshoghna Karma which means killing of disease producing microorganisms. Hence, it plays key role in prevention and cure of various infectious diseases.A similar process called fumigation is one of best and fastest method to maintain asepsis, antisepsis in wards and operation theatres of hospitals.Additionally, this study comprises critical literary review of herbomineral formulation named Yavasarshapadi Choorna which is indicated in form of incense for Dhoopana karma. It is indicated in Ayurvedic scripture Charaka Samhita in chapter Jatisutriya Sharir Adhyaya of Sharir Sthana. It was reviewed in context of sterilization activity to maintain asepsis and antisepsis. Specifically, it is indicated for fumigation of cloths and belongings of post-natal period of Women and that of the New born, Drug preparation room, New born care room, Surgical Procedure room modern surgery, traditional operation theatre sterilization was done by formalin gas fumigation over many decades which is found to have carcinogenic effect over human lives. Ayurvedic modality named Dhoopana was undertaken in current study as it is a safe and healthy alternative for sterilization.It overcomes harmful effects caused by modern sterilization method i.e. Formalin gas fumigation which is need of an hour. The Analytical study of antimicrobial and antifungal effect of various Ayurvedic Dhoopana Dravyas is the need of the hour along with preclinical and clinical study to verify Sterilization activity of various Ayurvedic Dhoopana Dravyas.

Analysis of Mutations and Dysregulated Pathways Unravels Carcinogenic Effect and Clinical Actionability of Mutational Processes

Somatic mutations accumulate over time in cancer cells as a consequence of mutational processes. However, the role of mutational processes in carcinogenesis remains poorly understood. Here, we infer the causal relationship between mutational processes and somatic mutations in 5,828 samples spanning 34 cancer subtypes. We found most mutational processes cause abundant recurrent mutations in cancer genes, while exceptionally ultraviolet exposure and altered activity of the error-prone polymerase bring a large number of recurrent non-driver mutations. Furthermore, some mutations are specifically induced by a certain mutational process, such as IDH1 p.R132H which is mainly caused by spontaneous deamination of 5-methylcytosine. At the pathway level, clock-like mutational processes extensively trigger mutations to dysregulate cancer signal transduction pathways. In addition, APOBEC mutational process destroys DNA double-strand break repair pathway, and bladder cancer patients with high APOBEC activity, though with homologous recombination proficient, show a significantly longer overall survival with platinum regimens. These findings help to understand how mutational processes act on the genome to promote carcinogenesis, and further, presents novel insights for cancer prevention and treatment, as our results showing, APOBEC mutagenesis and HRD synergistically contributed to the clinical benefits of platinum-based treatment.