Role of the Tristetraprolin (Zinc Finger Protein 36 Homolog) Gene in Cancer.

Cancer is a complicated transformational progression that fiercely changes the appearance of cell physiology as well as cells' relations with adjacent tissues. Developing an oncogenic characteristic requires a wide range of modifications in a gene expression at a cellular level. This can be achieved by activation or suppression of the gene regulation pathway in a cell. Tristetraprolin (TTP or ZFP36) associated with the initiation and development of tumors are regulated at the level of mRNA decay, frequently through the activity of AU-rich mRNA-destabilizing elements (AREs) located in their 3'-untranslated regions. TTP is an attractive target for therapeutic use and diagnostic tools due to its characteristic appearance in cancer tissue alone. Thus, the illumination of TTP in diverse types of cancer might deliver additional effective remedies in the coming era for cancer patients. The objective of this review is to familiarize the reader with the TTP proteins, focus on efficient properties that endow them with their effective oncogenic potential, describe their physiological role in cancer cells, and review the unique properties of TT, and of TTP-driven cancer.

Embarking Effect of ACE2-Angiotensin 1-7/Mas Receptor Axis in Benign Prostate Hyperplasia.

The proliferative cell process that causes prostate enlargement, obstruction of the bladder outlet, and lower urinary tract symptoms (LUTS) is known as benign prostatic hyperplasia (BPH). The prevalence of BPH worldwide is approximately 10%, 20%, 50%, and 80% for men in their 30s, 40s, 60s, and 70s, respectively. Recent data have revealed that overactivation of the renin angiotensin aldosterone system increases the level of bioactive peptide hormone angiotensin II, which downregulates the ACE2-angiotensin 1-7/Mas receptor axis path and upregulates angiotensin receptor type 1-mediated signaling, which finally leads to a proliferation of cellular elements in the prostate. We have hypothesized the mechanism that reverses the downregulation of the ACE2-angiotensin 1-7/Mas receptor axis path and the upregulation of angiotensin receptor type 1-mediated signaling. Thus, we posit that ACE2, Ang-(1-7), and the Mas receptor could be novel therapeutic targets for treating BPH/LUTS.

Formulation and characterization of oral rapid disintegrating tablets of levocetirizine.

BACKGROUND: Levocetirizine, active R (-) enantiomer of cetirizine, is an orally active and selective H1 receptor antagonist used medically as an anti-allergic. Allergic rhinitis is a symptomatic disorder of the nose induced by inflammation mediated by immunoglobulin E (IgE) in the membrane lining the nose after allergen exposure. OBJECTIVES: The purpose of the present study was to prepare rapidly disintegrating tablets of levocetirizine after its complexation with ß-cyclodextrin (ß-CD). MATERIAL AND METHODS: Levocetirizine-ß-CD complex tablets were prepared by direct compression technique using 3 synthetic superdisintegrants in different proportions. Development of the formulation in the present study was mainly based on the concentration of superdisintegrants and the properties of the drug. Nine batches of tablets were formulated and evaluated for various parameters: drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, hardness, friability, thickness uniformity, and in vitro dissolution. RESULTS: A Fourier-transform infrared spectroscopy (FTIR) study showed that there were no significant interactions between the drug and the excipients. The prepared tablets were good in appearance and showed acceptable results for hardness and friability. The in vitro disintegrating time of the formulated tablet batches was found to be 15-35 s percentage and the drug content of tablets in all formulations was found to be between 90-102%, which complied with the limits established in the United States Pharmacopeia. CONCLUSIONS: Complexation of levocetirizine with ß-CD significantly improves the solubility of the drug. The disintegration time of the tablets was decreased with an increase in superdisintegrant amount. The tablets (batch CPX5) had a minimum disintegration time of 20 s and 99.99% of the drug was released within 10 min.

Steam quality monitoring as a strategy to reduce wet packs and sterilization failure.

BACKGROUND: Hospital articles processed by steam are widely used in the Central Sterile Supply Department (CSSD), responsible for cleaning, disinfection, preparation, and sterilization. Steam sterilization is discussed worldwide, aiming to protect patients, and technical norms help to standardize the entire process. If steam is outside the specified requirements, the sterilization process may fail, resulting in the wet packs at the end of the sterilization cycle. AIM AND METHOD: The present study evaluated the steam quality at Santa Catarina Hospital (São Paulo, SP, Brazil) from 2016 to 2022. Saturated steam containing non-condensable gases, excess condensate, or even superheat was characterized using the methodology indicated in the European Standard EN285:2015. RESULTS: From 2016 to 2020, qualification tests showed that the saturated steam quality does not achieve standards limit parameters for non-condensable gases and dryness values. Infrastructural maintenance actions were taken to adjust the saturated steam quality. In 2021, the steam quality followed technical standards, and its adequacy was confirmed in 2022. CONCLUSION: The points developed by the hospital's maintenance department, following the relevant technical guidelines, the adoption of appropriate devices for this purpose, and the correct preventive maintenance in the autoclaves, together with the correct qualification of the equipment and proof of the steam quality contributed to improve the safety of the hospital sterilization process and reduce the incidence of wet packages.

Opening avenues for treatment of neurodegenerative disease using post-biotics: Breakthroughs and bottlenecks in clinical translation.

Recent studies have indicated the significant involvement of the gut microbiome in both human physiology and pathology. Additionally, therapeutic interventions based on microbiome approaches have been employed to enhance overall health and address various diseases including aging and neurodegenerative disease (ND). Researchers have explored potential links between these areas, investigating the potential pathogenic or therapeutic effects of intestinal microbiota in diseases. This article provides a summary of established interactions between the gut microbiome and ND. Post-biotic is believed to mediate its neuroprotection by elevating the level of dopamine and reducing the level of α-synuclein in substantia nigra, protecting the loss of dopaminergic neurons, reducing the aggregation of NFT, reducing the deposition of amyloid ß peptide plagues and ameliorating motor deficits. Moreover, mediates its neuroprotective activity by inhibiting the inflammatory response (decreasing the expression of TNFα, iNOS expression, free radical formation, overexpression of HIF-1α), apoptosis (i.e. active caspase-3, TNF-α, maintains the level of Bax/Bcl-2 ratio) and promoting BDNF secretion. It is also reported to have good antioxidant activity. This review offers an overview of the latest findings from both preclinical and clinical trials concerning the use of post-biotics in ND.

Analysis of water quality over non-condensable gases concentration on steam used for sterilization.

BACKGROUND: Non-condensable gases (NCGs) are all gases that do not undergo liquefaction during the saturated steam sterilization process. During a sterilization cycle, the NCGs presence inside the chamber is one of the biggest threats to the sterilization process compromising process validation and product quality. METHODS: In this work, 170 testing of NCGs concentrations performed between September 2016 and August 2021 were carried out by Orionce Serviços de Metrologia Ltda (Barueri, SP, Brazil), according to EN285:2015 procedure. For steam generation, the types of water used were softened water (SW), one-step reverse osmosis (RO), purified water (PW), and water for injection (WFI). The data obtained were analyzed using Minitab® software, version 18.1, to identify a relationship between the water quality used for steam generation and the concentration of non-condensable gases determined into equipment qualification. FINDINGS: From total tests performed, 109 tests passed, and 61 tests failed, representing 64.2% and 35.8%, respectively. A higher failure rate was observed in terms of concentration of non-condensable gases in systems that used purified water for steam generation (64.7%), followed by softened water (55.6%), one-step reverse osmosis (42.9%), and water for injection (7.6%). CONCLUSION: System processes using WFI for steam generation showed better results for steam quality approvement, in terms of NCGs concentration, compared to softened, purified, or reverse osmosis water treatments in the concentration of non-condensable gases in steam used for sterilization processes of industrial utilities.

Biomedical Applications of polymeric micelles in the treatment of diabetes mellitus: Current success and future approaches.

INTRODUCTION: Diabetes mellitus (DM) is the most common metabolic disease and multifactorial, harming patients worldwide. Extensive research has been carried out in the search for novel drug delivery systems offering reliable control of glucose levels for diabetics, aiming at efficient management of DM. AREAS COVERED: Polymeric micelles (PMs) as smart drug delivery nanocarriers are discussed, focusing on oral drug delivery applications for the management of hyperglycemia. The most recent approaches used for the preparation of smart PMs employ molecular features of amphiphilic block copolymers (ABCs), such as stimulus sensitivity, ligand conjugation, and as a more specific example the ability to inhibit islet amyloidosis. EXPERT OPINION: PMs provide a unique platform for self-regulated or spatiotemporal drug delivery, mimicking the working mode of pancreatic islets to maintain glucose homeostasis for prolonged periods. This unique characteristic is achieved by tailoring the functional chemistry of ABCs considering the physicochemical traits of PMs, including sensing capabilities, hydrophobicity, etc. In addition, the application of ABCs for the inhibition of conformational changes in islet amyloid polypeptide garnered attention as one of the root causes of DM. However, research in this field is limited and further studies at the clinical level are required.

Rubus rosaefolius extract as a natural preservative candidate in topical formulations.

Even though the synthetic preservatives may offer a high antimicrobial efficacy, they are commonly related to adverse reactions and regarded as having potentially harmful effects caused by chronic consumption. The development of natural preservatives provides a way of reducing the amount of synthetic preservatives normally used in pharmaceutical and cosmetic preparations. In addition, these agents have less toxic effects and represent a possible natural and safer alternative of the preservatives. The purpose of this research was to evaluate the Rubus rosaefolius Smith extract efficiency as a natural preservative in base formulations. Of the extract, 0.2% (w/w) was assayed for its effectiveness of antimicrobial protection in two different base formulations (emulsion and gel). The microbial challenge test was performed following the standard procedures proposed by The United States Pharmacopoeia 33nd, European Pharmacopoeia 6th, Japanese Pharmacopoeia 15th, and the Cosmetics, Toiletries, and Fragrance Association using standardized microorganisms. The results demonstrated that R. rosaefolius extract at the studied concentration reduced the bacterial inocula, satisfying the criterion in all formulations, even though it was not able to present an effective preservative behavior against fungi. Thus, the investigation of new natural substances with preservative properties that could be applied in pharmaceutical and cosmetic products is relevant due to the possibility of substituting or decreasing the concentration of synthetic preservatives, providing a way for the development of safer formulas for the use of consumers.

Validation and applicability of an alternative method for dialysis water and dialysate quality analysis.

INTRODUCTION: In hemodialysis, patients are exposed to a large volume of water, which may lead to fatal risks if not meeting quality standards. This study aimed to validate an alternative method for monitoring microbiological quality of treated water and assess its applicability in dialysis and dialysate analysis, to allow corrective actions in real-time. METHODS: Validation and applicability were analyzed by conventional and alternative methods. For validation, E. coli standard endotoxin was diluted with apyrogenic water in five concentrations. For the applicability analysis, treated water for dialysis was collected from different points in the treatment system (reverse osmosis, drainage canalization at the storage tank bottom, reuse, and loop), and dialysate was collected from four machines located in different rooms in the hemodialysis sector. RESULTS: The validation results were in accordance with the Brazilian Pharmacopoeia acceptance criteria, except for the last two concentrations analyzed. In addition, the ruggedness criterion performed under the US Pharmacopoeia was in agreement with the results. DISCUSSION: A limiting factor in the applicability analysis was the absence of the endotoxin maximum permitted level in dialysate by the Brazilian legislation. When comparing the analysis time, the alternative method was more time-consuming than the conventional one. This suggests that the alternative method is effective in the case of few analyses, that is, real-time analyses, favoring corrective actions promptly. On the other hand, it does not support the implementation of the alternative method in a laboratory routine due to the high demand for analyses.

Endotoxin test by recombinant Factor C for 0.9% sodium chloride injection

Endotoxin contamination is a threat to the safety of pharmaceutical products, especially parenteral drugs. Any sterile and/or pyrogen-free pharmaceutical product requires regulatory specifications to ensure safe patient use. This study covers the performance evaluation study of an endotoxin quantitation commercial kit by recombinant Factor C (rFC), Endozyme II® Go, for 0.9% sodium chloride injection. The samples were spiked with endotoxin solutions between 0.0005 and 10 EU/mL and tested by the rFC kit to evaluate precision, accuracy, detection and quantification limits, linearity, and robustness. Each of the six points was assayed at least five times.The relative standard deviation for precision testing ranged from 1.9 to 8.3%. The recovery accuracy values of endotoxin were between 61% and 125% for the range from 0.005 to 10 EU/mL. The results demonstrated that the rFC method allows endotoxin quantification with accuracy, precision, specificity, and linearity for the range of 0.005 and 10 EU/mL for 0.9% sodium chloride injection. (AU)

A contaminação por endotoxinas é uma ameaça à segurança dos produtos farmacêuticos, especialmente dos medicamentos parenterais. Qualquer produto farmacêutico estéril e/ou livre de pirogênios requer especificações regulatórias para garantir a segurança de uso para o paciente. Este estudo abrange o estudo de avaliação de desempenho empregando o kit comercial Endozyme II® Go para quantificação de endotoxina, por Fator C recombinante (FCr), em amostras de cloreto de sódio 0,9% para uso parenteral. As amostras foram fortificadas com cinco concentrações distintas de soluções de endotoxina na faixa entre 0,0005 e 10 UE/mL. Cada um dos cinco níveis foi testado pelo menos cinco vezes para avaliação dos critérios de precisão, exatidão, limites de detecção e quantificação, linearidade e robustez. O desvio padrão relativo para os testes de precisão variou de 1,9 a 8,3%. Os valores de recuperação de endotoxina para o parâmetro exatidão estiveram compreendidos entre 61% e 125%. Os resultados demonstraram que o método por FCr permite a quantificação de endotoxinas com exatidão, precisão, especificidade e linearidade para a faixa de 0,005 e 10 UE/mL em amostras de cloreto de sódio 0,9% para uso parenteral. (AU)

Multi-drug resistant Mycobacterium tuberculosis & oxidative stress complexity: Emerging need for novel drug delivery approaches.

Tuberculosis (caused by Mycobacterium tuberculosis, Mtb) treatment involves multiple drug regimens for a prolonged period. However, the therapeutic benefit is often limited by poor patient compliance, subsequently leading to treatment failure and development of antibiotic resistance. Notably, oxidative stress is a crucial underlying factor that adversely influences the various treatment regimens in tuberculosis. Little information is available with advanced drug delivery systems that could be effectively utilized, in particular, for targeting the oxidative stress in tuberculosis. Thus, this presents an opportunity to review the utility of various available, controlled-release drug delivery systems (e.g., microspheres, liposomes, niosomes, solid lipid nanoparticles, dendrimers) that could be beneficial in tuberculosis treatments. This will help the biological and formulation scientists to pave a new path in formulating a treatment regimen for multi-drug resistant Mtb.

Validation of erythromycin microbiological assay using an alternative experimental design.

The agar diffusion method, widely used in antibiotic dosage, relates the diameter of the inhibition zone to the dose of the substance assayed. An experimental plan is proposed that may provide better results and an indication of the assay validity. The symmetric or balanced assays (2 x 2) as well as those with interpolation in standard curve (5 x 1) are the main designs used in the dosage of antibiotics. This study proposes an alternative experimental design for erythromycin microbiological assay with the evaluation of the validation parameters of the method referring to linearity, precision, and accuracy. The design proposed (3 x 1) uses 3 doses of standard and 1 dose of sample applied in a unique plate, aggregating the characteristics of the 2 x 2 and 5 x 1 assays. The method was validated for erythromycin microbiological assay through agar diffusion, revealing its adequacy to linearity, precision, and accuracy standards. Likewise, the statistical methods used demonstrated their accordance with the method concerning the parameters evaluated. The 3 x 1 design proved to be adequate for the dosage of erythromycin and thus a good alternative for erythromycin assay.

Evaluating measurement uncertainty in the microbiological assay of vancomycin from methodology validation data.

Methodology validation and measurement uncertainty estimation are fundamental to obtain reliable results. The microbiological methods are widely used to determine antibiotic assay, as they permit evaluation of the analyzed antibiotic activity. A microbiological assay of vancomycin was performed with adoption of experimental design 5 x 1 (interpolation in 5-point standard curve assay) with final concentrations from 6.4 to 15.6 microg/mL (standards) and 10.0 microg/mL (sample). Bacillus subtitlis (ATCC 6633) was the microorganism used, with antibiotic medium No. 8 as base layer and inoculated layer. The plates were incubated at 37 degrees C for 18 h. The method adopted for the microbiological assay of vancomycin through agar diffusion was validated according to statistic results demonstrated for suitability of the method concerning linearity, precision, and accuracy. The estimated relative expanded uncertainty (4.3%) was considered adequate for this method purpose.

Reflection about the hemodialysis water microbiological quality in Brazil

Abstract Dialysis has been widely used in the treatment of patients with chronic kidney diseases and is considered a global public health issue. This treatment, which has changed the prognosis and quality of life in patients with chronic renal failure, can lead to complications that are often fatal. For this reason, there is a need for validation of alternative tests that favor the monitoring of treated water for dialysis in real-time to promote and prevent injuries to patients submitted to this procedure.

The effect of ozone gas sterilization on the properties and cell compatibility of electrospun polycaprolactone scaffolds.

The growing area of tissue engineering has the potential to alleviate the shortage of tissues and organs for transplantation, and electrospun biomaterial scaffolds are extremely promising devices for translating engineered tissues into a clinical setting. However, to be utilized in this capacity, these medical devices need to be sterile. Traditional methods of sterilization are not always suitable for biomaterials, especially as many commonly used biomedical polymers are sensitive to chemical-, thermal- or radiation-induced damage. Therefore, the objective of this study was to evaluate the suitability of ozone gas for sterilizing electrospun scaffolds of polycaprolactone (PCL), a polymer widely utilized in tissue engineering and regenerative medicine applications, by evaluating if scaffolds composed of either nanofibres or microfibres were differently affected by the sterilization method. The sterility, morphology, mechanical properties, physicochemical properties, and response of cells to nanofibrous and microfibrous PCL scaffolds were assessed after ozone gas sterilization. The sterilization process successfully sterilized the scaffolds and preserved most of their initial attributes, except for mechanical properties. However, although the scaffolds became weaker after sterilization, they were still robust enough to use as tissue engineering scaffolds and this treatment increased the proliferation of L929 fibroblasts while maintaining cell viability, suggesting that ozone gas treatment may be a suitable technique for the sterilization of polymer scaffolds which are significantly damaged by other methods.

Nephrotoxicity in Rats Exposed to Paracetamol: The Protective Role of Moralbosteroid, a Steroidal Glycoside.

Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Significant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential.

The Microbial Quality Aspects and Decontamination Approaches for the Herbal Medicinal Plants and Products: An in-Depth Review.

BACKGROUND: The present review article provides an overview of the published literature concerning microbial quality of medicinal plants and products and their decontamination methods. It is important to analyze different aspects regarding the cultivation, growing, harvesting, storage, manufacturing, and decontamination of medicinal plant products. Herbal medicinal plants bear a massive microbial load leading to contamination and mycotoxin, which needs to be considered, and properly controlled using suitable sterilization and decontamination methods. METHODS: The main focus of this review is on the definition, advantages, disadvantages and applications of decontamination methods, particularly to show that one must consider the characteristics of the initial sample to be decontaminated. RESULTS: The effects of various methods (ozone, plasma, irradiation) on medicinal herbs and products treated for microbiological decontamination are dependent on factors related to microbial load (i.e., nature and amount of initial contamination), herb/product matrix (i.e., complexity of chemical composition, physical state - solid or liquid) and treatment conditions (i.e., time, irradiation dose, absence or presence of oxygen). In addition, it is important to accept some loss of the chemical compounds, while decreasing microbial load to acceptable limits according to official herbal pharmacopoeias and literature, thus ensuring a final product with quality, safety and therapeutic efficacy. CONCLUSION: The conclusion, which comes from this contribution, is that herbal medicine has more contaminants than a chemically welldefined drug, thus, good manufacturing practices should be followed.

Ozone Gas as a Benign Sterilization Treatment for PLGA Nanofiber Scaffolds.

The use of electrospun nanofibers for tissue engineering and regenerative medicine applications is a growing trend as they provide improved support for cell proliferation and survival due, in part, to their morphology mimicking that of the extracellular matrix. Sterilization is a critical step in the fabrication process of implantable biomaterial scaffolds for clinical use, but many of the existing methods used to date can negatively affect scaffold properties and performance. Poly(lactic-co-glycolic acid) (PLGA) has been widely used as a biodegradable polymer for 3D scaffolds and can be significantly affected by current sterilization techniques. The aim of this study was to investigate pulsed ozone gas as an alternative method for sterilizing PLGA nanofibers. The morphology, mechanical properties, physicochemical properties, and response of cells to PLGA nanofiber scaffolds were assessed following different degrees of ozone gas sterilization. This treatment killed Geobacillus stearothermophilus spores, the most common biological indicator used for validation of sterilization processes. In addition, the method preserved all of the characteristics of nonsterilized PLGA nanofibers at all degrees of sterilization tested. These findings suggest that ozone gas can be applied as an alternative method for sterilizing electrospun PLGA nanofiber scaffolds without detrimental effects.

Application of the BacT/ALERTR 3D system for sterility testing of injectable products.

Sterility testing as described in the pharmacopoeia compendia requires a 14-day incubation period to obtain an analytical result. Alternative methods that could be applied to evaluating product sterility are especially interesting due to the possibility of reducing this incubation period and thus the associated costs. The aims of this study were to evaluate the performance of the BacT/ALERT(R) 3D system in detecting microorganisms in large-volume parenteral solutions that were intentionally contaminated and to compare this system to pharmacopoeia sterility testing using the membrane filtration method. The results indicated that there were no significant differences between the methods regarding the ability to detect microbial contamination; however, detection with the BacT/ALERT(R) 3D system was faster compared to the pharmacopoeia method. Therefore, the BacT/ALERT(R) 3D system is a viable alternative for assessing the sterility of injectable products.