Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

Predicting the main pollen season of Broussonetia Papyrifera (paper mulberry) tree.

Paper mulberry pollen, declared a pest in several countries including Pakistan, can trigger severe allergies and cause asthma attacks. We aimed to develop an algorithm that could accurately predict high pollen days to underpin an alert system that would allow patients to take timely precautionary measures. We developed and validated two prediction models that take historical pollen and weather data as their input to predict the start date and peak date of the pollen season in Islamabad, the capital city of Pakistan. The first model is based on linear regression and the second one is based on phenological modelling. We tested our models on an original and comprehensive dataset from Islamabad. The mean absolute errors (MAEs) for the start day are 2.3 and 3.7 days for the linear and phenological models, respectively, while for the peak day, the MAEs are 3.3 and 4.0 days, respectively. These encouraging results could be used in a website or app to notify patients and healthcare providers to start preparing for the paper mulberry pollen season. Timely action could reduce the burden of symptoms, mitigate the risk of acute attacks and potentially prevent deaths due to acute pollen-induced allergy.

Willow Bark (Salix spp.) Used for Pain Relief in Arthritis: A Meta-Analysis of Randomized Controlled Trials.

This study intends to assess the analgesic effects, physical facilitation, and safety of willow bark use in patients with arthritis. Our study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for relative randomized controlled trials (RCTs) describing the efficacy or adverse events of willow bark in patients with arthritis until 12 April 2023. We used Cochrane ROB 2.0 and the Grading of Recommendations, Assessment, Development, and Evaluations system to evaluate the quality of studies and evidence. The meta-analysis was carried out by the fix-effects model. This study included five studies with six RCTs consisting of 329 patients with arthritis. The results showed significant differences in pain relief and improvement in physical status for patients with arthritis between willow bark treatment and placebo groups, and no significant differences in the risk of all adverse events in patients with arthritis between willow bark treatment and placebo. Owing to the potential bias, the certainty and evidence of our findings are still inadequate. Therefore, further RCTs are needed to confirm our results.

Intravascular laser irradiation of blood as novel migraine treatment: an observational study.

BACKGROUND: Migraine is one of four major chronic diseases that cause disability. Decreases in regional cerebral blood flow (rCBF) occur during migraine attacks. Laser therapy is extensively employed in treating other vascular diseases; nevertheless, its effectiveness in migraine management remains largely unknown. Therefore, we evaluated the effect of low-level intravascular laser irradiation of blood (ILIB) therapy in patients with migraine. METHODS: We performed an observational case-control study in 24 patients suffering from migraine. Patients were divided into an ILIB treatment group and a traditional rehabilitation group. This study performed clinical assessments and single-photon emission computed tomography (SPECT) prior to and after the treatment and 1 month later. Changes in rCBF-SPECT between groups and between timepoints were compared to clinical outcomes. RESULTS: Nine patients undergoing rehabilitation and fifteen patients undergoing ILIB were studied from baseline to 1 month follow-up. The ILIB group, visual analog scale for pain (P = 0.001), Montreal Cognitive Assessment (P = 0.003), and Athens Insomnia Scale (P < 0.001) symptom scores significantly improved after treatment. SPECT imaging showed a 1.27 ± 0.27 fold increase in rCBF after ILIB treatment, and no significant differences in the rehabilitation group. CONCLUSIONS: Low-level ILIB therapy is associated with better clinical and vascular outcomes, and may be a feasible treatment option for migraine. Although our sample size was small, our data provide a starting point for migraine laser therapy research.

Phellinus linteus mycelia extract in COVID-19 prevention and identification of its key metabolic compounds profiling using UPLC-QTOF-MS/MS spectrometry.

For centuries, food, herbal medicines, and natural products have been valuable resources for discovering novel antiviral drugs, uncovering new structure-activity relationships, and developing effective strategies to prevent/treat viral infections. One such resource is Phellinus linteus, a mushroom used in folk medicine in Taiwan, Japan, Korea, and China. In this rich historical context, the key metabolites of Phellinus linteus mycelia ethanolic extract (GKPL) impacting the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at multiple stages have yet to be explored. Thus, this study systematically identifies and assesses the inhibitory effect of GKPL on the SARS-CoV-2 virus. Initially, the concentrations and contact times of GKPL against SARS-CoV-2 pseudovirus were assessed in HepG2 cells. Subsequently, utilizing the Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry method, potential biomarkers in the fungal extract were discerned. Metabolomic analysis identified 18 compounds in GKPL, with hispidin and hypholomine B present in the highest amounts. These compounds were isolated using chromatographic techniques and further identified through 1D NMR spectroscopic and mass spectrometry analysis. Hispidin and hypholomine B were found to inhibit the infection of SARS-CoV-2 pseudovirus by reducing angiotensin-converting enzyme 2 gene expression in HepG2, thereby decreasing viral entry. Moreover, hispidin and hypholomine B effectively block the spike receptor-binding domain, while hypholomine B, for the first time, showed significant inhibition of 3CL protease. This suggests that GKPL, enriched with hispidin and hypholomine B, has the potential to be used as an active ingredient against SARS-CoV-2.

Analgesic efficacy of collagen peptide in knee osteoarthritis: a meta-analysis of randomized controlled trials.

BACKGROUND: The management of knee osteoarthritis involves various treatment strategies. It is important to explore alternative therapies that are both safe and effective. Collagen peptides have emerged as a potential intervention for knee osteoarthritis. This study aims to evaluate the analgesic effects and safety of collagen peptide in patients diagnosed with knee osteoarthritis. METHODS: We conducted a systematic literature search following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases including PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published up to 27 May 2023 that focused on the analgesic outcomes and adverse events associated with collagen peptides or hydrolyzed collagen in patients with osteoarthritis. We assessed the quality of the included studies and the strength of evidence using the Cochrane ROB 2.0 tool and Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS: Four trials involving 507 patients with knee osteoarthritis were included and analyzed using the random-effects model. All these trials were considered to have a high risk of bias. Our results revealed a significant difference in pain relief between the collagen peptide group and the placebo group in patients with knee osteoarthritis (standardized mean difference: - 0.58; 95% CI - 0.98, - 0.18, p = 0.004; I2: 68%; quality of evidence: moderate). However, there was no significant difference in the risk of adverse events between collagen peptide and placebo (odds ratio: 1.66; 95% CI 0.99, 2.78, p = 0.05; I2: 0%; quality of evidence: very low). CONCLUSIONS: Our findings demonstrate significant pain relief in patients with knee osteoarthritis who received collagen peptides compared to those who received placebo. In addition, the risk of adverse events did not differ significantly between the collagen peptide group and the placebo group. However, due to potential biases and limitations, well-designed randomized controlled trials are needed to validate and confirm these findings.

Effect of Acupuncture on Recovery of Consciousness in Patients with Acute Traumatic Brain Injury: A Multi-Institutional Cohort Study.

Traumatic brain injury (TBI) causes cognitive dysfunction and long-term impairments. This study aims to examine the effectiveness of acupuncture on the recovery of consciousness in TBI patients. This is a retrospective, multi-institutional cohort study. We enrolled patients with newly diagnosed TBI from 1 January 2007 to 3 August 2021, aged 20 years and older, from the Chang Gung Research Database (CGRD). The outcome was defined based on the difference between the first and last Glasgow Coma Scale (GCS). A total of 2163 TBI patients were analyzed, and 237 (11%) received acupuncture in the treatment period. Generally, the initial GCS was lower in the acupuncture users (11 vs. 14). For the results of our study, a higher proportion of acupuncture patients achieved significant improvement (GCS differences ≥ 3) compared to non-acupuncture users (46.0% vs. 22.4%, p-value < 0.001). The acupuncture users had a 2.11 times higher chance of achieving a significant improvement when considering all assessable covariates (adjusted odds ratio (aOR) 2, 11, 95% confidence interval [CI]: 1.31-3.40; p-value = 0.002). Using 1:1 propensity score matching (PSM), the acupuncture users still had better outcomes than the non-acupuncture users (45.3% vs. 32.9%, p-value = 0.020). In conclusion, this study suggests that acupuncture treatment may be beneficial for TBI patients.

Association of asthma exacerbations with paper mulberry (Broussenetia papyrifera) pollen in Islamabad: An observational study.

Background: Although the role of airborne plant pollen in causing allergic rhinitis has been established, the association of concentrations of paper mulberry (Broussenetia papyrifera) pollens in the air and incidence of asthma exacerbations has not, despite an observed increase in the number of asthma patients attending physician clinics and hospital Accident and Emergency (A&E) Departments during the paper mulberry pollen season. We aimed to assess the association between paper mulberry pollen concentrations (typically peaking in March each year) and asthma exacerbations in the city of Islamabad. Methods: We used three approaches to investigate the correlation of paper mulberry pollen concentration with asthma exacerbations: A retrospective analysis of historical records (2000-2019) of asthma exacerbations of patients from the Allergy and Asthma Institute, Pakistan (n = 284), an analysis of daily nebulisations in patients attending the A&E Department of the Pakistan Institute of Medical Sciences (March 2020 to July 2021), a prospective peak expiratory flow rate (PEFR) diary from participants (n = 40) with or without asthma and with or without paper mulberry sensitisation. We examined associations between pollen data and asthma exacerbations using Pearson correlation. Results: We found a strong positive correlation between mean paper mulberry pollen counts and clinical records of asthma exacerbations in patients sensitised to paper mulberry (Pearson correlation coefficient (r) = 0.86; P < 0.001), but not in non-sensitised patients (r = 0.32; P = 0.3). There was a moderate positive correlation between monthly nebulisation counts and pollen counts (r = 0.56; P = 0.03), and a strong negative correlation between percent predicted PEFR and pollen counts in sensitised asthma patients (r = -0.72, P < 0.001). However, these correlations were of low magnitude in the non-sensitised asthma (r = -0.16; P < 0.001) and sensitised non-asthma (r = -0.28; P < 0.001) groups. Conclusions: Our three approaches to analysis all showed an association between high paper mulberry pollen concentration in Islamabad and asthma exacerbations. Predicting pollen peaks could enable alerts and mobilise strategies to proactively manage these peaks of asthma exacerbations.

Role of magnesium-L-Threonate in alleviating skin/muscle incision and retraction induced mechanical allodynia and anxiodepressive-like behaviors in male rats.

Chronic postsurgical pain (CPSP) and its emotional comorbidities poses health burden to patients who have received the surgical treatment. However, its underlying mechanism remains unclear. Emerging studies indicate that magnesium deficiency is associated with neurological diseases, and magnesium supplement confers protection under these disease conditions. In this study, we examined the role and mechanism of magnesium deficiency in the pathology of surgery-induced allodynia and negative emotion using a rat model of skin/muscle incision and retraction (SMIR) and investigated the therapeutic effects of magnesium supplementation by oral magnesium-L-Threonate (L-TAMS) in SMIR-injured rats. In the SMIR model, rats developed mechanical allodynia and anxiodepressive-like behaviors. Further, SMIR caused microglia and astrocyte activation and enhanced expression of pro-inflammatory cytokine (TNF-α, IL-1ß and IL-6) in the anterior cingulate cortex (ACC). Importantly, magnesium ion (Mg2+) levels decreased in the serum and cerebrospinal fluid (CSF) of SMIR-injured rats, which exhibited high correlation with pain and emotion behavioral phenotypes in these rats. Repeated oral administration of L-TAMS increased serum and CSF levels of Mg2+ in SMIR-injured rats. Notably, L-TAMS administration reversed SMIR-induced mechanical allodynia and anxiodepressive-like behaviors but did not affect pain and emotional behaviors in sham rats. Moreover, L-TAMS administration suppressed SMIR-caused glial activation and proinflammatory cytokine expression in the ACC but had no such effect in sham rats. Together, our study demonstrates the contributing role of magnesium deficiency in the pathology of surgery-induced chronic pain and negative emotion. Moreover, we suggest that L-TAMS might be a novel approach to treat CPSP and its emotional comorbidities.

Investigating the effects of Ceylon cinnamon water extract on HepG2 cells for Type 2 diabetes therapy.

Cinnamon and its extracts have been used as herbal remedies for many ailments, including for reducing insulin resistance and diabetes complications. Type 2 diabetes mellitus (T2DM) is a rapidly growing health concern around the world. Although many drugs are available for T2DM treatment, side effects and costs can be considerable, and there is increasing interest in natural products for managing chronic health conditions. Cinnamon may decrease the expression of genes associated with T2DM risk. The purpose of this study was to evaluate the effects of cinnamon water extract (CWE) compared with metformin on T2DM-related gene expression. HepG2 human hepatoma cells, widely used in drug metabolism and hepatotoxicity studies, were treated with different concentrations of metformin or CWE for 24 or 48 h. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and glucose uptake was compared in untreated and CWE- or metformin-treated cells under high-glucose conditions. Finally, total RNA was extracted and analyzed by RNA sequencing (RNA-seq), and bioinformatics analyses were performed to compare the transcriptional effects of CWE and metformin. We found cell viability was better in cells treated with CWE than in metformin-treated cells, demonstrating that CWE was not toxic at tested doses. CWE significantly increased glucose uptake in HepG2 cells, to the same degree as metformin (1.4-fold). RNA-seq data revealed CWE and metformin both induced significantly increased (1.3- to 1.4-fold) glucose uptake gene expression compared with untreated controls. Transcriptional differences between CWE and metformin were not significant. The effects of 0.125 mg mL-1 CWE on gene expression were comparable to 1.5 mg mL-1 (9.5 mM) metformin. In addition, gene expression at 0.125 mg mL-1 CWE was comparable to 1.5 mg mL-1 (9.5 mM) metformin. Our results reveal that CWE's effects on cell viability, glucose uptake, and gene expression in HepG2 cells are comparable to those of metformin, suggesting CWE may be an effective dietary supplement for mitigating T2DM-related metabolic dysfunction.

Enhanced recovery after surgery in transurethral surgery for benign prostatic hyperplasia.

Enhanced recovery after surgery (ERAS) measures have not been systematically applied in transurethral surgery for benign prostatic hyperplasia (BPH). This study was performed on patients with BPH who required surgical intervention. From July 2019 to June 2020, the ERAS program was applied to 248 patients, and the conventional program was applied to 238 patients. After 1 year of follow-up, the differences between the ERAS group and the conventional group were evaluated. The ERAS group had a shorter time of urinary catheterization compared with the conventional group (mean ± standard deviation [s.d.]: 1.0 ± 0.4 days vs 2.7 ± 0.8 days, P < 0.01), and the pain (mean ± s.d.) was significantly reduced through postoperative hospitalization days (PODs) 0-2 (POD 0: 1.7 ± 0.8 vs 2.4 ± 1.0, P < 0.01; POD 1: 1.6 ± 0.9 vs 3.5 ± 1.3, P < 0.01; POD 2: 1.2 ± 0.7 vs 3.0 ± 1.3, P < 0.01). No statistically significant difference was found in the rate of postoperative complications, such as postoperative bleeding (P = 0.79), urinary retention (P = 0.40), fever (P = 0.55), and readmission (P = 0.71). The hospitalization cost of the ERAS group was similar to that of the conventional group (mean ± s.d.: 16 927.8 ± 5808.1 Chinese Yuan [CNY] vs 17 044.1 ± 5830.7 CNY, P =0.85). The International Prostate Symptom Scores (IPSS) and quality of life (QoL) scores in the two groups were also similar when compared at 1 month, 3 months, 6 months, and 12 months after discharge. The ERAS program we conducted was safe, repeatable, and efficient. In conclusion, patients undergoing the ERAS program experienced less postoperative stress than those undergoing the conventional program.

Two new chromones and a new coumarin from the fruit of Cnidium monnieri (L.) Cusson.

Two new chromones named cnidimol G (1) and cnidimol H (2), one new coumarin, 7-methoxy-8-(3-methoxy-3-methyl-2-oxobutyl)coumarin (3), and twenty known compounds were isolated from MeOH extract of the fruit of Cnidium monnieri (L.) Cusson. The structures of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, HRESIMS, IR and UV. Anti-inflammatory activity of the selected isolated compounds were evaluated. Compounds 1 and 8 exhibited inhibitory activities against nitric oxide production.

[Different processed products of Polygonati Rhizoma treat Alzheimer's disease in rats: urine metabolomics based on UPLC-Q/TOF-MS].

The study investigated the effects of different processed products of Polygonati Rhizoma(black bean-processed Polygonati Rhizoma, BBPR; stewed Polygonati Rhizoma, SPR) on the urinary metabolites in a rat model of Alzheimer's disease(AD). Sixty SPF-grade male SD rats were randomized into a control group, a model group, a donepezil group, a BBPR group, and a SPR group, with twelve rats in each group. Other groups except the control group were administrated with D-galactose injection(100 mg·kg~(-1)) once a day for seven weeks. The control group was administrated with an equal volume of normal saline once a day for seven consecutive weeks. After three weeks of D-galactose injection, bilateral hippocampal Aß_(25-35) injections were performed for modeling. The rats were administrated with corresponding drugs(10 mL·kg~(-1)) by gavage since week 2, and the rats in the model and control group with an equal volume of double distilled water once a day for 35 continuous days. The memory behaviour and pathological changes in the hippocampal tissue were observed. The untargeted metabolites in the urine were detected by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS). Principal component analysis(PCA) and orthogonal partial least square-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites and potential biomarkers, for which the metabolic pathway enrichment analysis was conducted. The results indicated that BBPR and SPR increased the new object recognition index, shortened the escape latency, and increased the times of crossing the platform of AD rats in the Morris water maze test. The results of hematoxylin-eosin(HE) staining showed that the cells in the hippocampal tissue of the drug administration groups were closely arranged. Moreover, the drugs reduced the content of interleukin-6(IL-6, P<0.01) and tumor necrosis factor-α(TNF-α) in the hippocampal tissue, which were more obvious in the BBPR group(P<0.05). After screening, 15 potential biomarkers were identified, involving two metabolic pathways: dicoumarol pathway and piroxicam pathway. BBPR and SPR may alleviate AD by regulating the metabolism of dicoumarol and piroxicam.

Enhanced recovery after surgery in transurethral surgery for benign prostatic hyperplasia / 亚洲男科学杂志(英文版)

Enhanced recovery after surgery (ERAS) measures have not been systematically applied in transurethral surgery for benign prostatic hyperplasia (BPH). This study was performed on patients with BPH who required surgical intervention. From July 2019 to June 2020, the ERAS program was applied to 248 patients, and the conventional program was applied to 238 patients. After 1 year of follow-up, the differences between the ERAS group and the conventional group were evaluated. The ERAS group had a shorter time of urinary catheterization compared with the conventional group (mean ± standard deviation [s.d.]: 1.0 ± 0.4 days vs 2.7 ± 0.8 days, P < 0.01), and the pain (mean ± s.d.) was significantly reduced through postoperative hospitalization days (PODs) 0-2 (POD 0: 1.7 ± 0.8 vs 2.4 ± 1.0, P < 0.01; POD 1: 1.6 ± 0.9 vs 3.5 ± 1.3, P < 0.01; POD 2: 1.2 ± 0.7 vs 3.0 ± 1.3, P < 0.01). No statistically significant difference was found in the rate of postoperative complications, such as postoperative bleeding (P = 0.79), urinary retention (P = 0.40), fever (P = 0.55), and readmission (P = 0.71). The hospitalization cost of the ERAS group was similar to that of the conventional group (mean ± s.d.: 16 927.8 ± 5808.1 Chinese Yuan [CNY] vs 17 044.1 ± 5830.7 CNY, P =0.85). The International Prostate Symptom Scores (IPSS) and quality of life (QoL) scores in the two groups were also similar when compared at 1 month, 3 months, 6 months, and 12 months after discharge. The ERAS program we conducted was safe, repeatable, and efficient. In conclusion, patients undergoing the ERAS program experienced less postoperative stress than those undergoing the conventional program.

Experiences of Middle-Aged and Older Taiwanese Adults With Chronic Insomnia: A Descriptive Qualitative Study.

The purpose of the current study was to describe the experiences of middle-aged and older adults with chronic insomnia. A descriptive qualitative study design was used, and semi-structured interviews were conducted with 17 participants from two primary clinic health centers in northern Taiwan. Mean age of participants was 64.3 years, most (58.8%) participants were middle aged (aged 40 to 64 years), and mean duration of insomnia was 5.6 years. Three themes emerged: Imperfection of Lived Experience, Dilemma of Whether to Take a Hypnotic, and Seeking Help from Alternative Therapy. Participants believed chronic insomnia contributed to an accumulation of anxiety and negative emotions, resulting in psychological burden. For participants with insomnia, because of their negative impressions of hypnotics, they usually sought alternative therapies to improve sleep. Health care providers should endeavor to understand the needs of individuals with insomnia and provide them with sleep hygiene knowledge and assistance in safe sleep practices. [Journal of Gerontological Nursing, 48(11), 21-28.].

Ibuprofen treatment ameliorates memory deficits in rats with collagen-induced arthritis by normalizing aberrant MAPK/NF-κB and glutamatergic pathways.

Many studies have indicated that the risk of cognitive impairment is higher in patients with rheumatoid arthritis (RA). Additionally, patients with RA may have a lower incidence of cognitive impairment with long-term use of ibuprofen. This study was aimed at investigating the impacts of RA on memory function and the mechanisms that ibuprofen may exhibit to improve memory function in rats with collagen-induced arthritis (CIA). Ibuprofen (30 mg/kg) was given twice daily to CIA rats for two weeks starting from Day 18 following the first immunization. Memory function was measured by the Morris water maze (MWM) test and long-term potentiation (LTP). The proinflammatory cytokine levels and downstream signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), were examined. Furthermore, the glutamatergic system, including glutamate transporters/receptors and brain extracellular levels of glutamate, was investigated. The results showed that the impaired learning memory in CIA rats, examined by the MWM test and LTP, can be ameliorated by ibuprofen treatment. Along with the improvement in memory deficits, ibuprofen attenuated both neuroinflammation and the associated elevated levels of phosphorylated p38, JNK, and p65 in the hippocampus of CIA rats. In addition, the decreased excitatory amino acid transporter 2 level, the increased extracellular glutamate, and the upregulated hippocampal NMDA receptor 2B of CIA rats were all normalized by ibuprofen treatment. These findings suggest that the effect of ibuprofen on the memory improvement in CIA rats is associated with the normalization of the activated MAPK and NF-κB pathways and the aberrant glutamatergic system.

Diterpene promptly executes a non-canonical autophagic cell death in doxorubicin-resistant lung cancer.

16-hydroxycleroda-3,13-dien-15,16-olide (HCD) has antitumor activity reported in numerous types of cancers. However, the efficacy of HCD treatment in non-small-cell lung cancer (NSCLC) cells and doxorubicin-resistant (Dox-R)-NSCLC cells remains to be unraveled. The underlying anti-cancer mechanism of HCD on Dox-R and Dox-sensitive (Dox-S) of A549 cells was also investigated. Cytotoxicity of HCD against two cell lines (Dox-S and Dox-R) were determined via MTT assay, flow cytometry, and Western blot. A further examination of its anti-cancer efficacy was performed in A549-bearing xenograft mice via orthotopic intratrachea (IT) inoculation, which showed that HCD could arrest both Dox-S and Dox-R cells at G2/M phase without altering the sub-G1 cycle along with increasing of cleaved-PARP. HCD downregulated the mTOR/Akt/PI3K-p85 and PI3K-ClassIII/Beclin-1 signals and upregulated p62/LC3-I/II expressions to further confirm that the cell autophagy of NSCLC cells after being HCD-induced. Morphological observations of mouse lung sections illustrated that fewer cancer cells accumulated close to the trachea while less neoplastic activities were found in HCD orthotopic treated mice without liver, kidney, and spleen toxicity. Lastly, Dox, HCD, and target therapy medicines of EGFR and ALK were nicely docked with EGFR, ALK, and mTOR. Conclusively, HCD was demonstrated the chemotherapeutic potential regardless of Dox-R and Dox-S cells, suggesting natural autophagic inducer HCD provides a promising lead compound for new drug discovery and development of lung cancer therapies.

Identification of Bioactive Components of Stephania epigaea Lo and Their Potential Therapeutic Targets by UPLC-MS/MS and Network Pharmacology.

Stephania epigaea, an important traditional folk medicinal plant, elucidating its bioactive compound profiles and their molecular mechanisms of action on human health, would better understand its traditional therapies and guide their use in preclinical and clinical. This study aims to detect the critical therapeutic compounds, predict their targets, and explore potential therapeutic molecular mechanisms. This work first determined metabolites from roots, stems, and flowering twigs of S. epigaea by a widely targeted metabolomic analysis assay. Then, the drug likeness of the compounds and their pharmacokinetic profiles were screened by the ADMETlab server. The target proteins of active compounds were further analyzed by PPI combing with GO and KEGG cluster enrichment analysis. Finally, the interaction networks between essential compounds, targets, and disease-associated pathways were constructed, and the essential compounds binding to their possible target proteins were verified by molecular docking. Five key target proteins (EGFR, HSP90AA1, SRC, TNF, and CASP3) and twelve correlated metabolites, including aknadinine, cephakicine, homostephanoline, and N-methylliriodendronine associated with medical applications of S. epigaea, were identified, and the compounds and protein interactions were verified. The key active ingredients are mainly accumulated in the root, which indicates that the root is the main medicinal tissue. This study demonstrated that S. epigaea might exert the desired disease efficacy mainly through twelve components interacting via five essential target proteins. EGFR is the most critical one, which deserves further verification by biological studies.

Nephrocalcinosis in children who received high-dose vitamin D.

BACKGROUND: Vitamin D supplements are readily available as over-the-counter preparations. However, although rare, cases of vitamin D overdose still occur and are associated with nephrocalcinosis and life-threatening hypercalcemia. Errors in manufacturing of nutritional supplements may be a cause of vitamin D intoxication in children. This study aimed to identify factors associated with vitamin D overdose-related nephrocalcinosis in children due to manufacturing errors in supplements. METHODS: This retrospective study reviewed medical charts of pediatric patients with non-registered supplement-related vitamin D overdose at a tertiary referral hospital between 2006 and 2011. Clinical and laboratory characteristics of patients with or without nephrocalcinosis were evaluated. Receiver operating characteristics curve and area under the receiver operating characteristics curve were used to determine the most predictive value of each characteristic. RESULTS: A total of 44 patients (males: 29; age: 7-62 months) were included. Age ≤ 16.5 months, body weight ≤ 10.25 kg, body height ≤ 78.5 cm, body surface area (BSA) ≤ 0.475 m2, 25-hydroxyvitamin D3 ≥ 143 ng/mL, and calcium ≥ 10.65 mg/dL were predictive of developing nephrocalcinosis with a sensitivity and specificity of > 60%. Univariant analysis revealed that BSA was the most significant anthropometric prognostic factor (odds ratio: 12.09; 95% confidence interval: 2.61-55.72; P = 0.001). CONCLUSIONS: Children with smaller BSAs were more vulnerable to high-dose vitamin D3-related nephrocalcinosis. Physicians and parents should be aware of the potential adverse effects of vitamin D overdose in children. A higher resolution version of the Graphical abstract is available as Supplementary information.