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Urologia Feb 2024The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination... (Review)
Review
The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination of curcumin (CURC) and ursolic acid (UA). We investigate this combination using a systematic review process to assess the most likely mechanistic pathway and human testing in prostate cancer. We used the PRISMA statement to screen titles, abstracts, and the full texts of relevant articles and performed a descriptive analysis of the literature reviewed for study inclusion and consensus of the manuscript. The most common molecular and cellular pathway from articles reporting on the pathways and effects of CURC ( = 173) in prostate cancer was NF-κB ( = 25, 14.5%). The most common molecular and cellular pathway from articles reporting on the pathways and effects of UA ( = 24) in prostate cancer was caspase 3/caspase 9 ( = 10, 41.6%). The three most common molecular and cellular pathway from articles reporting on the pathways and effects of both CURC and UA ( = 193) in prostate cancer was NF-κB ( = 28, 14.2%), Akt ( = 22, 11.2%), and androgen ( = 19, 9.6%). Therefore, we have identified the potential synergistic target pathways of curcumin and ursolic acid to involve NF-κB, Akt, androgen receptors, and apoptosis pathways. Our review highlights the limited human studies and specific effects in prostate cancer.
Topics: Male; Humans; Ursolic Acid; Curcumin; NF-kappa B; Signal Transduction; Proto-Oncogene Proteins c-akt; Apoptosis; Triterpenes; Prostatic Neoplasms
PubMed: 37776274
DOI: 10.1177/03915603231202304 -
Frontiers in Pharmacology 2023Ciprofol (HSK3486) is a novel intravenous anesthetic agent that bears structural similarity to propofol and displays favorable pharmacodynamic characteristics such as...
Ciprofol (HSK3486) is a novel intravenous anesthetic agent that bears structural similarity to propofol and displays favorable pharmacodynamic characteristics such as rapid onset and offset. The meta-analysis aimed at comparing the efficacy and safety of ciprofol versus propofol in clinical practice. Medline, EMBASE, Google Scholar, Cochrane Library were searched from inception to April 2023. The primary outcome was success rate of sedation/anesthetic induction and differences in sedation/induction time. The secondary outcomes included risks of hemodynamic instability, respiratory complications, and pain on injection, as well as recovery profiles, satisfaction score, and top-up dose requirement. Twelve RCTs (sedation: = 6, anesthetic induction, = 6, all conducted in China) involving 1,793 patients (age: 34-58 years) published from 2021 to 2023 were analyzed. Pooled results revealed no differences in success rate [risk ratio (RR) = 1, 95% confidence interval (CI): 0.99 to 1.01, I = 0%, 1,106 patients, = 1] and time required for successful anesthetic induction/sedation [mean difference (MD) = 7.95 s, 95% CI: -1.09 to 16.99, I = 97%, 1,594 patients, = 0.08]. The risks of top-up dose requirement (RR = 0.94, = 0.48), cardiopulmonary complications [i.e., bradycardia (RR = 0.94, = 0.67), tachycardia (RR = 0.83, = 0.68), hypertension (RR = 1.28, = 0.2), hypoxemia/pulmonary depression (RR = 0.78, = 0.24)], and postoperative nausea/vomiting (RR = 0.85, = 0.72), as well as discharge time (MD = 1.39 min, = 0.14) and satisfaction score (standardized MD = 0.23, = 0.16) did not differ significantly between the two groups. However, the ciprofol group had lower risks of hypotension (RR = 0.85, = 0.02) and pain on injection (RR = 0.17, < 0.00001) than the propofol group. The time to full alertness was statistically shorter in the propofol group (i.e., 0.66 min), but without clinical significance. Our results demonstrated similar efficacy between ciprofol and propofol for sedation and anesthetic induction, while ciprofol was associated with lower risks of hypotension and pain on injection. Future studies are warranted to evaluate the efficacy and safety of ciprofol in pediatric or the elderly populations. (https://www.crd.york.ac.uk/prospero/), identifier (CRD42023421278).
PubMed: 37818194
DOI: 10.3389/fphar.2023.1225288 -
Cells Jan 2023Chronic inflammation has been closely linked to the development and progression of various cancers. The epithelial-mesenchymal transition (EMT) is a process involving... (Review)
Review
Chronic inflammation has been closely linked to the development and progression of various cancers. The epithelial-mesenchymal transition (EMT) is a process involving the acquisition of mesenchymal features by carcinoma cells and is an important link between inflammation and cancer development. Inflammatory mediators in the tumour micro-environment, such as cytokines and chemokines, can promote EMT changes in cancer cells. The aim of this systematic review is to analyse the effect of cytokines on EMT in gynaecological cancers and discuss their possible therapeutic implications. A search of the databases CINAHL, Cochrane, Embase, Medline, PubMed, TRIP, and Web of Science was performed using the keywords: "cytokines" AND "epithelial mesenchymal transition OR transformation" AND "gynaecological cancer". Seventy-one articles reported that various cytokines, such as TGF-β, TNF-α, IL-6, etc., promoted EMT changes in ovarian, cervical, and endometrial cancers. The EMT changes included from epithelial to mesenchymal morphological change, downregulation of the epithelial markers E-cadherin/β-catenin, upregulation of the mesenchymal markers N-cadherin/vimentin/fibronectin, and upregulation of the EMT-transformation factors (EMT-TF) /. Cytokine-induced EMT can lead to gynaecological cancer development and metastasis and hence novel therapies targeting the cytokines or their EMT signalling pathways could possibly prevent cancer progression, reduce cancer recurrence, and prevent drug-resistance.
Topics: Female; Humans; Cytokines; Epithelial-Mesenchymal Transition; Neoplasm Recurrence, Local; Genital Neoplasms, Female; Transforming Growth Factor beta; Tumor Microenvironment
PubMed: 36766756
DOI: 10.3390/cells12030416 -
Clinical and Translational Science Dec 2023Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals'... (Review)
Review
Clinical implementation of pharmacogenomic (PGx)-guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals' (HCPs) and consumers' knowledge, attitudes, perspectives, and education needs to inform strategies for implementation of scalable and sustainable oncology PGx programs. Systematic review of original articles indexed in EMBASE, EMCARE, MEDLINE, and PsycInfo from January 2012 until June 2022, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using the Mixed Methods Appraisal Tool. PROSPERO registration number CRD42022352348. Of 1442 identified studies; 23 met inclusion criteria with 87% assessed high quality. Of these, 52% reported on HCPs, 35% on consumers, and 13% on both HCPs and consumers. Most were conducted in the United States (70%) and included multiple cancer types (74%). Across studies, HCPs and consumers mostly perceived value in PGx, however, both groups reported barriers to utilization, including cost, lack of consistent recommendations across guidelines, and limited knowledge among HCPs; test accuracy, clear testing benefits, and genomic information confidentiality among consumers. HCPs and consumers value and want to engage in PGx strategies in oncology care, however, are inhibited by unmet needs and practice and knowledge gaps. Implementation strategies aimed at addressing these issues may best support increased PGx uptake in oncology practice.
Topics: Humans; Pharmacogenetics; Health Knowledge, Attitudes, Practice; Health Personnel; Medical Oncology; Neoplasms
PubMed: 37991131
DOI: 10.1111/cts.13672 -
Journal of Pineal Research May 2022The melatonin system and circadian disruption have well-established links with aggressive behaviors; however, the biological underpinnings have not been thoroughly... (Review)
Review
The melatonin system and circadian disruption have well-established links with aggressive behaviors; however, the biological underpinnings have not been thoroughly investigated. Here, we aimed at examining the current knowledge regarding the neurobiological and psychopharmacological involvement of the melatonin system in aggressive/violent behaviors. To this end, we performed a systematic review on Embase and Pubmed/MEDLINE of preclinical and clinical evidence linking the melatonin system, melatonin, and melatoninergic drugs with aggressive/violent behaviors. Two blinded raters performed an independent screening of the relevant literature. Overall, this review included 38 papers distributed between clinical and preclinical models. Eleven papers specifically addressed the existing evidence in rodent models, five in fish models, and 21 in humans. The data indicate that depending on the species, model, and timing of administration, melatonin may exert a complex influence on aggressive/violent behaviors. Particularly, the apparent contrasting findings on the link between the melatonin system and aggression/violence (with either increased, no, or decreased effect) shown in preclinical models underscore the need for further research to develop more accurate and fruitful translational models. Likewise, the significant heterogeneity found in the results of clinical studies does not allow yet to draw any firm conclusion on the efficacy of melatonin or melatonergic drugs on aggressive/violent behaviors. However, findings in children and in traits associated with aggressive/violent behavior, including irritability and anger, are emerging and deserve empirical attention given the low toxicity of melatonin and melatonergic drugs.
Topics: Aggression; Animals; Melatonin; Violence
PubMed: 35192237
DOI: 10.1111/jpi.12794 -
Alcoholism, Clinical and Experimental... Feb 2017Decades of alcohol research have established the health risks and pharmacodynamic profile of oral alcohol consumption. Despite isolated periods of public health concern,... (Review)
Review
Decades of alcohol research have established the health risks and pharmacodynamic profile of oral alcohol consumption. Despite isolated periods of public health concern, comparatively less research has evaluated exposure to alcohol vapor. Inhaled alcohol initially bypasses first-pass metabolism and rapidly reaches the arterial circulation and the brain, suggesting that this route of administration may be associated with pharmacological effects that increase the risk of addiction. However, detailed reviews assessing the possible effects of inhaled alcohol in humans are lacking. A comprehensive, systematic literature review was conducted using Google Scholar and PubMed to examine manuscripts studying exposure to inhaled alcohol and measurement of biomarkers (biochemical or functional) associated with alcohol consumption in human participants. Twenty-one publications reported on alcohol inhalation. Fourteen studies examined inhalation of alcohol vapor associated with occupational exposure (e.g., hand sanitizer) in a variety of settings (e.g., naturalistic, laboratory). Six publications measured inhalation of alcohol in a controlled laboratory chamber, and 1 evaluated direct inhalation of an e-cigarette with ethanol-containing "e-liquid." Some studies have reported that inhalation of alcohol vapor results in measurable biomarkers of acute alcohol exposure, most notably ethyl glucuronide. Despite the lack of significantly elevated blood alcohol concentrations, the behavioral consequences and subjective effects associated with repeated use of devices capable of delivering alcohol vapor are yet to be determined. No studies have focused on vulnerable populations, such as adolescents or individuals with alcohol use disorder, who may be most at risk of problems associated with alcohol inhalation.
Topics: Administration, Inhalation; Adolescent; Alcohol Drinking; Animals; Central Nervous System Depressants; Electronic Nicotine Delivery Systems; Ethanol; Humans; Vaping
PubMed: 28054395
DOI: 10.1111/acer.13291 -
Pharmaceutics Feb 2023Rivaroxaban has been widely used to prevent and treat various thromboembolic diseases for more than a decade. However, whether a lower dose of rivaroxaban is required... (Review)
Review
Rivaroxaban has been widely used to prevent and treat various thromboembolic diseases for more than a decade. However, whether a lower dose of rivaroxaban is required for Asians is still debatable. This review aimed to explore the potential ethnic difference in pharmacokinetic/pharmacodynamic (PK/PD) characteristics between Asians and Caucasians. A systematic search was conducted and twenty-four studies were identified, of which 10 were conducted on Asian adults, 11 on predominantly Caucasian adults, and 3 on Caucasian pediatrics. The apparent clearance (CL/F) of rivaroxaban in Caucasian adults with non-valvular atrial fibrillation (6.45-7.64 L/h) was about 31-43% higher than that in Asians (4.46-5.98 L/h) taking 10~20 mg rivaroxaban every 24 h. Moreover, there was no obvious difference in CL/F among Japanese, Chinese, Thai, and Irani people. Regarding PK/PD relationship, prothrombin time was linked to rivaroxaban concentration in a linear or near-linear manner, and Factor Xa activity was linked with the E model. The exposure-response relationship was comparable between Asians and Caucasians. Renal function has a significant influence on CL/F, and no covariate was recognized for exposure-response relationship. In conclusion, a lower dose of rivaroxaban might be required for Asians, and further studies are warranted to verify this ethnic difference to facilitate optimal dosing regimens.
PubMed: 36839909
DOI: 10.3390/pharmaceutics15020588 -
Pharmacoepidemiology and Drug Safety Aug 2016In order to identify challenges in pediatric pharmacoepidemiological safety studies, we assessed the characteristics of such (published) studies. (Review)
Review
PURPOSE
In order to identify challenges in pediatric pharmacoepidemiological safety studies, we assessed the characteristics of such (published) studies.
METHODS
Relevant articles from inception to 2013 were retrieved from Embase and Medline. We sequentially screened titles, abstracts and full texts with independent validation. We systematically collected data regarding general information, study methods and results.
RESULTS
Out of 4825 unique articles, 268 full texts (5.6%) were retained; 147 (54.9%) pertained to drugs rather than vaccines. Considering the 268 studies, 202 (75.4%) concerned children and adolescents (2 to 11 years) and 14 (5.3%) included preterm newborns. Most studies originated from North America (154 [57.5%]) or Europe (92 [34.3%]). Only 47 studies (17.5%) were privately funded. The majority (174 [64.9%]) were cohort studies. Out of 268 studies, 196 (73.1%) collected data retrospectively; paper medical charts were the most common data source for the exposures (85 [31.7%]) and outcomes (122 [45.5%]). Only 3 (2.0%) drug-only studies investigated rarely used drugs. Considering all 268 studies, only 27 (10.1%) reported sample size or power calculation. Most (75 [51.0%]) drug-only studies corrected confounding by multivariate modeling unlike stratification in 66 (55.9%) vaccine-only studies. Considering 75 child-only studies without any statistically significant result, 41 (54.7%) did not discuss lack of power.
CONCLUSIONS
Although the field of pediatric pharmacoepidemiology is steadily developing evaluation seldom includes neonates, is mainly focused on few drug classes and safety outcomes and concerns mainly drug use in developed countries. Small study size is a specific challenge in pediatrics. Reporting should be improved. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.
Topics: Adolescent; Child; Confounding Factors, Epidemiologic; Data Collection; Drug-Related Side Effects and Adverse Reactions; Epidemiologic Research Design; Humans; Infant, Newborn; Multivariate Analysis; Pediatrics; Pharmacoepidemiology; Research Support as Topic
PubMed: 27255559
DOI: 10.1002/pds.4041 -
Journal of Medicine and Life Mar 2022The COVID-19 pandemic has tremendously increased the production and sales of disinfectants. This study aimed to systematically review and analyze the efficacy and safety... (Review)
Review
The COVID-19 pandemic has tremendously increased the production and sales of disinfectants. This study aimed to systematically review and analyze the efficacy and safety of chlorine dioxide as a disinfectant. The literature relating to the use of chlorine dioxide as a disinfectant was systematically reviewed in January 2021 using databases such as PubMed, Science Direct, and Google Scholar. Inclusion criteria were studies that investigated the use of chlorine dioxide to assess the efficacy, safety, and impact of chlorine dioxide as a disinfectant. Out of the 33 included studies, 14 studies focused on the disinfectant efficacy of chlorine dioxide, 8 studies expounded on the safety and toxicity in humans and animals, and 15 studies discussed the impact, such as water treatment disinfection using chlorine dioxide. Chlorine dioxide is a safe and effective disinfectant, even at concentrations as low as 20 to 30 mg/L. Moreover, the efficacy of chlorine dioxide is mostly independent of pH. Chlorine dioxide can be effectively used to disinfect drinking water without much alteration of palatability and can also be used to destroy pathogenic microbes, including viruses, bacteria, and fungi from vegetables and fruits. Our review confirms that chlorine dioxide is effective against the resistant , H1N1, and other influenza viruses. Studies generally support the use of chlorine dioxide as a disinfectant. The concentration deemed safe for usage still needs to be determined on a case-by-case basis.
Topics: Animals; COVID-19; Chlorine; Chlorine Compounds; Disinfectants; Humans; Influenza A Virus, H1N1 Subtype; Oxides; Pandemics
PubMed: 35449999
DOI: 10.25122/jml-2021-0180 -
Current Neuropharmacology 2023Traditional medicine and biomedical sciences are reaching a turning point because of the constantly growing impact and volume of Big Data. Machine Learning (ML)...
Traditional medicine and biomedical sciences are reaching a turning point because of the constantly growing impact and volume of Big Data. Machine Learning (ML) techniques and related algorithms play a central role as diagnostic, prognostic, and decision-making tools in this field. Another promising area becoming part of everyday clinical practice is personalized therapy and pharmacogenomics. Applying ML to pharmacogenomics opens new frontiers to tailored therapeutical strategies to help clinicians choose drugs with the best response and fewer side effects, operating with genetic information and combining it with the clinical profile. This systematic review aims to draw up the state-of-the-art ML applied to pharmacogenomics in psychiatry. Our research yielded fourteen papers; most were published in the last three years. The sample comprises 9,180 patients diagnosed with mood disorders, psychoses, or autism spectrum disorders. Prediction of drug response and prediction of side effects are the most frequently considered domains with the supervised ML technique, which first requires training and then testing. The random forest is the most used algorithm; it comprises several decision trees, reduces the training set's overfitting, and makes precise predictions. ML proved effective and reliable, especially when genetic and biodemographic information were integrated into the algorithm. Even though ML and pharmacogenomics are not part of everyday clinical practice yet, they will gain a unique role in the next future in improving personalized treatments in psychiatry.
Topics: Humans; Pharmacogenetics; Precision Medicine; Machine Learning; Mental Disorders; Psychiatry
PubMed: 37559539
DOI: 10.2174/1570159X21666230808170123