Drug Discoveries and Therapeutics最新文献

Docosahexaenoic acid (DHA; 22:6n-3), an n-3 polyunsaturated fatty acid, has various important roles in brain functions. Nitric oxide (NO) produced by neuronal NO synthase (nNOS) and Ca²⁺/calmodulindependent protein kinase II (CaMKII) is also involved in brain functions. We investigated the influence of DHA on nNOS and CaMKII protein expression in differentiated NG108-15 cells. NG108-15 cells were seeded in 12-well plates, and after 24 h, the medium was replaced with Dulbecco's modified Eagle's medium containing 1% fetal bovine serum, 0.2 mM dibutyryl cyclic adenosine monophosphate and 100 nM dexamethasone as differentiation-inducing medium. When cells were cultured in differentiation-inducing medium, neurite-like outgrowths were observed on days 5 and 6. However, no significant difference in morphology was observed in cells with or without DHA treatment. With or without DHA addition, nNOS protein expression was increased on days 5 and 6 compared with day 0. This increase tended to be enhanced by DHA. CaMKII protein expression did not change after differentiation without DHA, but was significantly increased on day 6 compared with day 0 with DHA addition. These data indicate that DHA is involved in brain functions by regulating CaMKII and nNOS protein expression.

Diospyrobezoar is a relatively uncommon cause of small bowel obstruction. Here we report successful treatment in a patient with small bowel obstruction due to diospyrobezoar by laparoscopic-assisted surgery. A 93-year-old woman who had undergone distal gastrectomy and laparoscopic cholecystectomy presented with nausea and anorexia. An intestinal obstruction and an intestinal intraluminal mass were discovered on abdominal enhanced computed tomography. Following a transnasal ileus tube placement, the patient underwent laparoscopic surgery to remove the diospyrobezoar from the small intestine. The postoperative course of the patient was uneventful. Laparoscopic-assisted surgery following the transnasal ileus tube was beneficial for the patient's small bowel obstruction caused by diospyrobezoar.

The interruption of anticancer infusion processes in patients undergoing chemotherapy may affect their quality of life and the efficacy and safety of the therapy. We experienced several interruptions of carboplatin infusion in multiple patients receiving paclitaxel-carboplatin combination therapy. Therefore, we investigated the causes of these interruptions. The filter and catheter surfaces were evaluated by scanning electron microscopy. Moreover, using a texture analyzer, the mechanical strengths of catheter-attached syringes were compared pre- and post-administration. We observed that the syringe pushing force requirement was higher following dripping failure. However, precipitates were not evident on the filter surfaces, regardless of the dripping failure route. In this case, some of the drug adhered to the catheters' surfaces and interrupted the carboplatin titration. Consequently, in patients receiving combination therapy with paclitaxel and carboplatin, and experiencing interruptions in carboplatin infusion, attention should be paid to the catheter.

The use of harmful solvents during the preparation of pharmaceutical formulations is restricted to preserve environment and ensure safety of industrial operations. However, harmful solvents must be used to produce certain formulations. For instance, methylene chloride has been used in the fabrication of polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) microspheres. This review highlights the latest advances in the strategy of PLA or PLGA microsphere production from non-halogenated solvents and describes advantages and limitations of these methods. The study also discusses the development of dry fabrication techniques for microsphere fabrication and the positioning of conventional and dry fabrication in the containment concept for workers' safety.

Since itching without rash frequently among older adults' population, study about skin properties of itching without rash is important to develop prevention methods. Therefore, this study explored the skin properties related to itching without rash and the factors associated with them. A correlation, predictive designs study was conducted at Indonesian Long-term Care (LTC) facilities. Skin properties including skin barrier function and skin inflammation were examined by photographs (macroscopic and microscopic), stratum corneum (SC) hydration, skin Potential of Hydrogen (pH), and skin blotting. Itching experience and skincare behavior were obtained by questionnaire. The itching-related skin properties and associated factors were analyzed. A total of 405 residents participated in this study, with mean age was 74 years. The prevalence of itching on the whole body was 69.1%, and 50.3% of those manifesting itching on the left forearm involved itching without macroscopic abnormalities (itching without rash). SC hydration, skin pH, albumin and nerve growth factor β (NGFβ) were associated with itching without rash (p = 0.007, 0.012, < 0.001, and < 0.001, respectively). Additionally, factors associated with skin properties were age, sex, sun exposure experience, skincare, and hygiene care in the linear regression analysis. Measurement of skin biomarkers using skin blotting was a possible objective measurement of itching skin properties without rash regardless of the environmental condition.

Traditional medicines are recently being focused on to treat diabetes and its complications because of their lack of toxic and/or side effects. This report describes the effects of 7-O-galloyl-D-sedoheptulose (GS), a polyphenolic compound isolated from Corni Fructus, on type 2 diabetic db/db mice with hepatic and pancreatic damage. We examined several biochemical factors and oxidative stress- and inflammation-related markers. In the serum, levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, and interleukin-6 were down-regulated, while adiponectin was augmented by GS treatment. In addition, GS suppressed the reactive oxygen species and lipid peroxidation in the serum, liver, and pancreas, but increased the pancreatic insulin and pancreatic C-peptide contents. These results were derived from attenuating the expression of nicotinamide adenine dinucleotide phosphate oxidase subunit proteins, Nox-4 and p22^phox. Augmented nuclear factor (NF)-E2-related factor 2 and heme oxygenase-1 were reduced with a decrease in oxidative stress during GS treatment. NF-κB-related pro-inflammatory factors were also alleviated in hepatic tissue. Moreover, GS modulated the protein expressions of pro-inflammatory NF-κB, cyclooxygenase-2, inducible nitric oxide synthase, c-Jun N-terminal kinase (JNK), phosphor-JNK, activator protein-1, transforming growth factor-β₁, and fibronectin. Based on these results, we demonstrated that the anti-diabetic action of GS may be due to its anti-oxidative stress property and anti-inflammatory action.

The majority of cervical cancer cases are contributed to chronic infection with high-risk human papillomavirus (HPV), while only a fraction of infected women finally develop cancer. It is suggested that apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A), a type of mRNA editing enzyme, may be involved in the development and progression of HPV-related tumors. This study aimed to explore the role and potential mechanisms of APOBEC3A in cervical cancer. First, the expression levels, prognostic values and genetic alterations of APOBEC3A in cervical cancer were explored using various bioinformatics tools and databases. Then, functional enrichment analyses were performed. Finally, genetic polymorphisms (rs12157810 and rs12628403) of APOBEC3A were genotyped in our clinical sample of 91 cervical patients. The associations between APOBEC3A polymorphisms and clinical characteristics as well as patient overall survival were further evaluated. Compared with normal tissues, the expression level of APOBEC3A was significantly elevated in cervical cancer. High expression of APOBEC3A had better survival compared with the low expression group. The immunohistochemistry results showed that the expression of APOBEC3A protein was localized in the nucleus. APOBEC3A expression level in cervical and endocervical cancer (CESC) was negatively correlated with the infiltration level of cancer-associated fibroblasts, and positively correlated with the infiltration level of gamma delta T cells. No association was observed between APOBEC3A polymorphisms and patient survival. The expression of APOBEC3A was significantly higher in cervical cancer tissues, while high expression was associated with better prognosis in cervical cancer patients. APOBEC3A has the potential of being used in prognostic evaluation in cervical cancer patients.

Oxidative stress, glycation and inflammation are the main causes of many severe diseases. To date, no single extract has been shown to simultaneously inhibit these three reactions. In this study, the antioxidant, antiglycation and anti-inflammatory activities of ethanol extracts from four edible plants that are commonly used as Thai folk medicine were compared. Among these extracts, Caesalpinia mimosoides extract (CME) showed the highest antioxidant potential with Trolox equivalent antioxidant activity (TEAC) of 5.9 ± 0.1 mM/mg followed closely by Zingiber officinale extract (ZOE) with a TEAC value of 5.4 ± 0.2 mM/mg. However, CME showed no cytotoxicity, whereas ZOE greater than 60 μg/mL showed cytotoxicity to normal human cells. Antiglycation assay using bovine serum albumin-ribose showed comparable potency between CME and Spondias dulcis extract (SDE). However, CME exhibited a high anti-inflammatory activity, significantly higher than SDE and activity depending on the dose. At a concentration of 60 μg/mL, approximately 85% of the interleukin-6 pro-inflammatory cytokine produced from human monocytes, induced by lipopolysaccharides, was completely inhibited by CME whereas SDE showed no inhibition. In summary, CME is the most potential extract with simultaneously activity of these three reactions. CME has the highest total phenolic content expressed as gallic acid equivalent to 301 ± 8 mg/g. Identification using high-performance liquid chromatography revealed the presence of at least four phenolic compounds, gallic acid, syringic acid, p-coumaric acid, and ellagic acid are existed in CME. Our finding suggests that CME is a promising natural source for inhibition of oxidative stress, glycation, and inflammation.

With the in-depth study of the human genome and the increasing popularity of gene sequencing, it has been gradually confirmed that genetics can play a crucial role in infertility. To provide references for clinical treatment, we have focused on genes and drug therapy for genetic infertility. This review recommends adjuvant therapy and drug substitution. Examples of these therapies include antioxidants (such as folic acid, vitamin D, vitamin E, inositol, coenzyme Q10 etc.), metformin, anticoagulants, levothyroxine, dehydroepiandrosterone, glucocorticoids, and gonadotropins etc. Based on the pathogenesis, we provide an overview of the current knowledge, including randomized controlled trials and systematic reviews, and predict potential target genes and signaling pathways, proposing possible future strategies for the use of targeted drugs to treat infertility. Non-coding RNAs are anticipated to become a novel target for the treatment of reproductive illnesses since they have a significant role in controlling the occurrence and development of reproductive diseases.

This study aimed to explore the factors influencing subjective health views based on the living conditions and concerns of university students during the coronavirus infection 2019 (COVID-19) pandemic. From March to April 2021, a questionnaire survey was administered to 8,547 Japanese university students, and logistic regression analysis was used to explore factors related to subjective health views. The results showed that satisfaction with quality of sleep (OR = 2.651, 95% Cl 2.370-2.966,p < 0.001), satisfaction with university life (OR = 2.486, 95%Cl 2.215-2.789, p < 0.001), satisfaction with diet (OR = 1.849, 95% CI: 1.496-2.285, p < 0.001), regular exercise (OR = 1.759, 95% CI: 1.594-1.941, p < 0.001), consciousness of nutritional balance (OR = 1.276, 95% CI: 1.147-1.420,p < 0.001), eating breakfast every day (OR = 1.247, 95% CI: 1.121-1.387, p < 0.001), and consuming soft drinks at least once a week (OR = 0.865, 95% CI: 0.755-0.966, p = 0.010) were positive factors for subjective views of health. On the other hand, anxiety about whether the necessary credits can be obtained (OR = 0.885, 95% CI: 0.799-0.980, p = 0.019), infection from minimal outings (OR = 0.881, 95% CI: 0.794-0.976, p = 0.016) building and maintaining friendships on campus (OR = 0.867, 95% CI: 0.767-0.980, p = 0.023), and being able to continue working (OR = 0.713, 95% CI: 0.640-0.795, p < 0.001) were identified as negative factors. To ensure a healthy university life during the COVID-19 pandemic or future pandemic, supports tailored to students' living conditions and measures to address their anxieties are required.