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Bioengineered Dec 2021Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a...
Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a candidate mechanism involving relevant biological processes. We therefore constructed a ceRNA network using the TCGA and GEO database, to determine the potential mechanisms of microbiota-mediated colorectal carcinogenesis and progression. We found a total of 75 lncRNAs, 8 miRNAs, and 9 mRNAs in the probiotics-mediated ceRNA network and a total of 49 lncRNAs, 4 miRNAs, and 3 mRNA in the pathobiont-mediated ceRNA network, which could induce the microbiota-mediated carcinogenesis and progression. The GO and KEGG analysis indicated that the ceRNA network is mainly enriched in the metabolic process, and two unique pathways (the p53 signaling pathway and microRNA in cancer), respectively. A four-gene signature (FRMD6-AS2, DIRC3, LIFR-AS1, and MRPL23-AS1) was suggested as an independent prognostic factor. Four lncRNAs (LINC00355, KCNQ1OT1, LINC00491, and HOTAIR) were associated with poor survival. Three small molecule candidate anticancer drugs (Pentoxyverine, Rimexolone, and Doxylamine) were identified. A four-gene signature (FAM129A, BCL2, PMAIP1, and RPS6) is significantly correlated with immune infiltration level. This study provides a promising biomarker reservoir to explore the mechanism by which microbiota regulate the ceRNA network involving the immune response, and further participate in colorectal carcinogenesis and progression.
Topics: Antineoplastic Agents; Colorectal Neoplasms; Computational Biology; Gastrointestinal Microbiome; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Prognosis; Protein Interaction Maps; RNA, Messenger; RNA, Untranslated
PubMed: 34227920
DOI: 10.1080/21655979.2021.1940614 -
American Journal of Obstetrics and... Jul 2021Obstetrical healthcare providers frequently field questions about the safety of medications recommended or prescribed to their pregnant patients. Most women use as least... (Review)
Review
Obstetrical healthcare providers frequently field questions about the safety of medications recommended or prescribed to their pregnant patients. Most women use as least 1 medication during pregnancy; however, there is little information about the safety or appropriate dosing of many medications during this phase of life. In addition, the development of drugs for use in pregnant women trails behind the development of drugs intended for other sectors of the population. Our goal is to inform the obstetrics community about the US Food and Drug Administration authority and their role in approving drugs for marketing. We begin with the statutes that led to the creation of the Food and Drug Administration and its current organization. We then cover drug development and the Food and Drug Administration review process, including the role of the advisory committee. The different types of drug approvals are discussed, with some specific examples. Finally, we enumerate the drugs specifically approved for use in obstetrics and contrast them with drugs commonly used by pregnant women and drugs used "off-label" during pregnancy. The Food and Drug Administration is committed to protecting and advancing the public health of pregnant women by guiding the development and ensuring the availability of effective and safe therapeutics for obstetrical indications and for medical conditions during pregnancy. We hope this review will inspire more research addressing drug use during pregnancy.
Topics: Animals; Clinical Trials as Topic; Drug Approval; Female; Fetus; Humans; Lactation; Pregnancy; Pregnancy Complications; Prescription Drugs; Risk Assessment; Teratogens; United States; United States Food and Drug Administration
PubMed: 34215352
DOI: 10.1016/j.ajog.2021.02.032 -
Journal of Hazardous Materials Sep 2021The potential of Iris pseudacorus and the associated periphytic biofilm for biodegradation of two common pharmaceutical contaminants (PCs) in urban wastewater was...
The potential of Iris pseudacorus and the associated periphytic biofilm for biodegradation of two common pharmaceutical contaminants (PCs) in urban wastewater was assessed individually and in consortium. An enhanced removal for sulfamethoxazole (SMX) was achieved in consortium (59%) compared to individual sets of I. pseudacorus (50%) and periphytic biofilm (7%) at concentration of 5 mg L. Conversely, individual sets of periphytic biofilm (77%) outperformed removal of doxylamine succinate (DOX) compared to individual sets of I. pseudacorus (59%) and consortium (67%) at concentration of 1 mg L. Enhanced relative abundance of microflora containing microalgae (Sellaphora, Achnanthidium), rhizobacteria (Acidibacter, Azoarcus, Thioalkalivibrio), and fungi (Serendipita) in periphytic biofilm was observed after treatment. SMX treatment for five days elevated cytochrome P450 enzymes' expressions, including aniline hydroxylase (48%) and aminopyrine N-demethylase (54%) in the periphytic biofilm. Nevertheless, I. pseudacorus showed 175% elevation of aniline hydroxylase along with other biotransformation enzymes, such as peroxidase (629%), glutathione S-transferase (514%), and dichloroindophenol reductase (840%). A floating bed phytoreactor planted with I. pseudacorus and the periphytic biofilm consortium removed 67% SMX and 72% DOX in secondary wastewater effluent. Thus, the implementation of this strategy in constructed wetland-based treatment could be beneficial for managing effluents containing PCs.
Topics: Biofilms; Iris Plant; Nitrogen; Pharmaceutical Preparations; Wastewater
PubMed: 34118536
DOI: 10.1016/j.jhazmat.2021.126349 -
The Australian & New Zealand Journal of... Aug 2021We conducted an online survey of 249 Australian women who currently or previously experienced severe nausea and vomiting of pregnancy (NVP) or hyperemesis gravidarum...
We conducted an online survey of 249 Australian women who currently or previously experienced severe nausea and vomiting of pregnancy (NVP) or hyperemesis gravidarum (HG) and examined their experiences in being denied medications during pregnancy. One in four women reported being denied medications for NVP/HG, which most commonly involved doxylamine and encounters with community pharmacists. Women's experiences reflected that lack of awareness of guidelines and unfavourable risk-benefit assessments appeared to be key barriers to facilitating medication access. Approaches towards identifying and effectively addressing barriers to the provision of effective treatments for severe NVP and HG are urgently needed.
Topics: Antiemetics; Australia; Female; Humans; Hyperemesis Gravidarum; Nausea; Pregnancy; Pregnant Women
PubMed: 33984156
DOI: 10.1111/ajo.13359 -
The Medical Journal of Australia Apr 2021
Topics: Antiemetics; Australia; Doxylamine; Female; Humans; Morning Sickness; Pregnancy
PubMed: 33629372
DOI: 10.5694/mja2.50969 -
Maedica Dec 2020Prescribing drugs in pregnancy is a challenging approach for doctors. To evaluate drugs used in pregnancy. A prospective, cross-sectional, descriptive study was carried...
Prescribing drugs in pregnancy is a challenging approach for doctors. To evaluate drugs used in pregnancy. A prospective, cross-sectional, descriptive study was carried out by collecting and evaluating prescriptions on various parameters. More than 50% of antenatal care attendees belonged to the 18-24 age group, and 102 (41.46%) were primigravidae. The main presenting complaints were abdominal pain (25.16%), followed by nausea and vomiting (22.60%) and fever (11.14%); the maximum number of visits to hospital was seen in the first trimester (40.53%), followed by the third trimester (38.42%). It was observed that 25.78% of prescriptions did not contain any medicine. The average number of prescribed medicines was 2.32, with the lowest in the first trimester (1.77) and the highest in the second trimester (2.78). It was noticed that 74.11% and 71.26% of all prescribed medicines were from essential medicine list and generics, respectively. Of all prescribed drugs, 11.52% were antimicrobials, and 4.11% injectable dosage forms. Vitamins and minerals were the preferred prescribed medicines (34.82%), followed by antimicrobial agents (11.52%) and doxylamine plus pyridoxine (10.16%). Also, doctors who made the drug choice during antenatal visits were more confident in evidence-based safety as per New Pregnancy and Lactation Rule (PPLR); 45.37% of drugs were prescribed from category A, followed by 38.25% from category B and none from group X. Doctors were concerned about prescribing safer drugs in pregnancy and were more confident in evidence-based medication.
PubMed: 33603908
DOI: 10.26574/maedica.2020.15.4.503 -
Frontiers in Microbiology 2020Pharmaceutical contaminants (PCs) have been recognized as emerging contaminants causing unexpected consequences to environment and humans. There is an urgent need for...
Pharmaceutical contaminants (PCs) have been recognized as emerging contaminants causing unexpected consequences to environment and humans. There is an urgent need for development of efficient technologies to treat these PCs from water. The current study has investigated the removal capacity of a green microalgal species, , for doxylamine, chemical oxygen demand (COD), and nutrients from real wastewater. Results have indicated that can grow well in the doxylamine-polluted wastewater with the achievement of 56, 78.5, 100, and 89% removal of doxylamine, COD, total nitrogen (TN), and total phosphorus (TP). Addition of 2 g L bicarbonate enhanced the removal of doxylamine up to 63% and slightly inhibited the removal of COD. Decreased carbohydrate (28-26%) and increased protein content (30-33%) of the harvested biomass have been observed after cultivation in the wastewater. The current study has shown the feasibility of using microalgae-based biotechnologies for PC-contaminated wastewater.
PubMed: 33224120
DOI: 10.3389/fmicb.2020.584020 -
Spectrochimica Acta. Part A, Molecular... Feb 2021The combination of pyridoxine HCl (PYR) and doxylamine succinate (DOX) was proved to be effective and safe acting as the first line of pregnancy medication for vomiting...
In vitro analytical dissolution profiling of antiemetic delayed release tablets in two different dissolution media: Validated spectrophotometric methods versus reported HPLC.
The combination of pyridoxine HCl (PYR) and doxylamine succinate (DOX) was proved to be effective and safe acting as the first line of pregnancy medication for vomiting and nausea under a trade name; Vomibreak® delayed release tablets. This combination has been available in the Egyptian market since 2016. Dissolution study is a meaningful tool that represents a predictor of output because the rate controlling steps in any drug's absorption is the rate of discharging from its medicinal formulation. Generally, the dissolution test of all delayed release tablets is operated at two stages: first the acid stage then the buffer stage. In our work, the acid stage was performed in 0.1 N hydrochloric acid (0.1 M HCl) and the buffer one was in 0.2 M sodium phosphate buffer (0.2 M Na-PB), pH = 6.8, according to FDA guidelines. In present work, for the first time, this binary mixture was quantitatively determined by applying four spectrophotometric methods. PYR was directly determined by zero order spectra method (D) at 291.0 nm in the range 2.0-26.0 μg/mL in the acid stage and at 325.0 nm in the range 5.0-35.0 μg/mL in the buffer stage, where DOX show no interference in both cases. However, DOX was determined by three methods, namely, Dual wavelength (DW), Ratio difference (RD) and Derivative ratio (DD). DD was the chosen method for determination of DOX in the two-phase dissolution study of Vomibreak® tablets at 249.0 nm in the range 2.0-44.0 μg/mL and 273.0 nm in the range 5.0-100.0 μg/mL in acid and buffer phases, respectively. All of the suggested methods were tested in compliance with ICH guidelines, where all methods were found to be reliable, reproducible, and selective. A statistical comparison was computed between two analytical techniques of critical importance in the development of two media dissolution profile: proposed UV- spectrophotometric and reported HPLC methods where no significant difference was found. Difference (ƒ) and similarity (ƒ) factors were calculated for PYR and DOX and shown that ƒ was 1.490 and 1.654 and ƒ was 94.431 and 92.396 for PYR and DOX, respectively.
Topics: Antiemetics; Chromatography, High Pressure Liquid; Egypt; Female; Humans; Pregnancy; Solubility; Tablets
PubMed: 33049467
DOI: 10.1016/j.saa.2020.119013 -
Pharmacological Research Jan 2021Because observational studies often use imperfect measurements, results are prone to misclassification errors. We used as a motivating example the possible teratogenic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Because observational studies often use imperfect measurements, results are prone to misclassification errors. We used as a motivating example the possible teratogenic risks of antiemetic agents in pregnancy since a large observational study recently showed that first-trimester exposure to doxylamine-pyridoxine was associated with significantly increased risk of congenital malformations as a whole, as well as central nervous system defects, and previous observational studies did not show such associations. A meta-analysis on this issue was carried out with the aim to illustrate how differential exposure and outcome misclassifications may lead to uncertain conclusions.
METHODS
Medline, searched to October 2019 for full text papers in English. Summary Odds Ratios (ORs) with confidence intervals (CIs) were calculated using random-effect models. Probabilistic sensitivity analyses were performed for evaluating the extension of differential misclassification required to account for the exposure-outcome association.
RESULTS
Summary ORs were 1.02 (95 % CI, 0.92-1.15), 0.99 (0.82-1.19) and 1.25 (1.08-1.44) for overall congenital, cardiocirculatory, and central nervous system malformations respectively. By assuming exposure and outcome bias factor respectively of 0.95 (i.e., newborns with congenital defects had exposure specificity 5% lower than healthy newborns) and 1.12 (i.e., exposed newborns had outcome sensitivity 12 % higher than unexposed newborns), summary OR of central nervous system defects became 1.13 (95 % CI, 0.99-1.29) and 1.17 (95 % CI, 0.99-1.38).
CONCLUSION
Observational investigations and meta-analyses of observational studies need cautious interpretations. Their susceptibility to several, often sneaky, sources of bias should be carefully evaluated.
Topics: Abnormalities, Drug-Induced; Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Nausea; Observational Studies as Topic; Odds Ratio; Pregnancy; Pyridoxine; Scientific Experimental Error; Uncertainty; Vomiting
PubMed: 33031909
DOI: 10.1016/j.phrs.2020.105229