Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis/Autophagy/Lysosome Axis.

Periodontitis development arises from the intricate interplay between bacterial biofilms and the host's immune response, where macrophages serve pivotal roles in defense and tissue homeostasis. Here, we uncover the mitigative effect of copper chelator Tetrathiomolybdate (TTM) on periodontitis through inhibiting cuproptosis, a newly identified form of cell death which is dependent on copper. Our study reveals concurrent cuproptosis and a macrophage marker within murine models. In response to lipopolysaccharide (LPS) stimulation, macrophages exhibit elevated cuproptosis-associated markers, which are mitigated by the administration of TTM. TTM treatment enhances autophagosome expression and mitophagy-related gene expression, countering the LPS-induced inhibition of autophagy flux. TTM also attenuates the LPS-induced fusion of autophagosomes and lysosomes, the degradation of lysosomal acidic environments, lysosomal membrane permeability increase, and cathepsin B secretion. In mice with periodontitis, TTM reduces cuproptosis, enhances autophagy flux, and decreases Ctsb levels. Our findings underscore the crucial role of copper-chelating agent TTM in regulating the cuproptosis/mitophagy/lysosome pathway during periodontitis inflammation, suggesting TTM as a promising approach to alleviate macrophage dysfunction. Modulating cuproptosis through TTM treatment holds potential for periodontitis intervention.

Comparative Effectiveness of Different Exercises for Reducing Pain Intensity in Primary Dysmenorrhea: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Studies have demonstrated that exercise can mitigate the intensity of menstrual pain in primary dysmenorrhea, but the most effective type of exercise remains unclear. The objective of this systematic review and network meta-analysis was to evaluate the effectiveness of different exercise regimens in reducing pain associated with primary dysmenorrhoea. METHODS: Randomized controlled trials investigating the relationship between menstrual pain and exercise were selected from major electronic databases until February 2, 2024. The primary outcome was the effect of exercise on pain intensity measured by the mean difference on a 10-cm visual analogue scale at 4 and 8 weeks after intervention. The secondary outcome was the difference in risk of dropout at 8 weeks. The study protocol was registered as INPLASY202330050. RESULTS: This systematic review and network meta-analysis included 29 randomized controlled trials, which involved 1808 participants with primary dysmenorrhea. Exercise interventions included relaxation exercise, strength training, aerobic activity, yoga, mixed exercise, and the Kegel maneuver. Relaxation exercise was the most effective in reducing menstrual pain in 4 weeks (- 3.56; 95% confidence interval: - 5.03 to - 2.08). All exercise interventions were effective in reducing menstrual pain at 8 weeks, with reductions ranging from - 3.87 (95% CI - 5.51 to - 2.22) for relaxation exercise to - 2.75 (95% CI - 4.00 to - 1.51) for yoga, compared to the control group. Relaxation exercises were found to have a significantly lower dropout risk (- 0.11; 95% CI - 0.20 to 0.02), while none of the exercise types was associated with a higher dropout risk than the control group. CONCLUSION: All exercise interventions were effective in reducing menstrual pain in primary dysmenorrhea after 8 weeks of intervention. However, relaxation exercise was found to be the most effective intervention at 4 and 8 weeks and had the lowest risk of dropout.

This analysis aimed to see how effective different types of exercise are in reducing pain in women with primary dysmenorrhea. The researchers looked at 29 studies involving 1808 participants and evaluated six different types of exercise. The main outcome was the effect of pain reduction after 4 and 8 weeks of exercise. The researchers found that all types of exercise were effective in reducing menstrual pain after 8 weeks, with relaxation exercises being the most effective at both 4 and 8 weeks. None of the exercise types were associated with higher dropout risks than the control group, and relaxation exercise had a lower dropout risk than the other types of exercise.

Acetyl-CoA-dependent ac4C acetylation promotes the osteogenic differentiation of LPS-stimulated BMSCs.

The impaired osteogenic capability of bone marrow mesenchymal stem cells (BMSCs) caused by persistent inflammation is the main pathogenesis of inflammatory bone diseases. Recent studies show that metabolism is disturbed in osteogenically differentiated BMSCs in response to Lipopolysaccharide (LPS) treatment, while the mechanism involved remains incompletely revealed. Herein, we demonstrated that BMSCs adapted their metabolism to regulate acetyl-coenzyme A (acetyl-CoA) availability and RNA acetylation level, ultimately affecting osteogenic differentiation. The mitochondrial dysfunction and impaired osteogenic potential upon inflammatory conditions accompanied by the reduced acetyl-CoA content, which in turn suppressed N4-acetylation (ac4C) level. Supplying acetyl-CoA by sodium citrate (SC) addition rescued ac4C level and promoted the osteogenic capacity of LPS-treated cells through the ATP citrate lyase (ACLY) pathway. N-acetyltransferase 10 (NAT10) inhibitor remodelin reduced ac4C level and consequently impeded osteogenic capacity. Meanwhile, the osteo-promotive effect of acetyl-CoA-dependent ac4C might be attributed to fatty acid oxidation (FAO), as evidenced by activating FAO by L-carnitine supplementation counteracted remodelin-induced inhibition of osteogenesis. Further in vivo experiments confirmed the promotive role of acetyl-CoA in the endogenous bone regeneration in rat inflammatory mandibular defects. Our study uncovered a metabolic-epigenetic axis comprising acetyl-CoA and ac4C modification in the process of inflammatory osteogenesis of BMSCs and suggested a new target for bone tissue repair in the context of inflammatory bone diseases.

Differential Impact of Exercises on Quality-of-Life Improvement in Breast Cancer Survivors: A Network Meta-Analysis of Randomized Controlled Trials.

This study aimed to assess the effectiveness of various exercise interventions in enhancing the quality of life for breast cancer survivors. To achieve this, randomized controlled trials were identified from major electronic databases, focusing on the relationship between exercise and quality of life in breast cancer survivors. The primary outcome was the impact of exercise on quality of life 12 weeks after the intervention, with a secondary outcome comparing dropout rates between intervention groups and a regular care control group. The study protocol was registered with INPLASY (INPLASY202340007). A network meta-analysis of nine randomized controlled trials involving 725 participants was conducted, examining aerobic and strength training, aerobic activity, yoga, and strength exercise. Results showed that aerobic and strength training was the most effective intervention, significantly improving the quality of life of breast cancer survivors (1.31; 95% confidence interval: 0.49 to 2.12). Aerobic activity had a borderline effect (0.83; 0.03 to 1.63), while no exercise interventions were associated with an increased dropout risk compared to the control group (regular care). The study concluded that concurrent aerobic and strength training can improve breast cancer survivors' quality of life after 12 weeks of intervention without increasing dropout risk compared to regular care.

Preliminary outcomes of accelerated partial breast irradiation by interstitial multicatheter brachytherapy with intraoperative free-hand catheter implantation in early breast cancer.

BACKGROUND: To evaluate the clinical feasibility of interstitial brachytherapy by intraoperative free-hand catheter implantation in the treatment of early breast cancer after breast-conserving surgery (BCS). METHODS: Between January 2018 and December 2019, 44 patients with early breast cancer after BCS who met the inclusion criteria ≥45 years old, invasive carcinoma ≤3 cm or ductal carcinoma in situ <2.5 cm, estrogen receptor positive, lymph node negative, surgical margin negative, no distant metastasis, and an ECOG performance score ≤1 were enrolled in this phase II single-arm study. The postoperative irradiation field includes the tumor bed plus 2-cm margin in all directions, except in the anterior-posterior direction. The total prescribed tumor dose was 3400 cGy delivered in 10 fractions twice daily at 6-hour intervals. The primary endpoints were acute side effects, late treatment-related toxicity, and cosmetic outcome. The secondary endpoints were local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: The median follow-up time was 33.5 months (mean, 32.9 months; range, 20-43 months). The cosmetic results were good to very good in 92.3% of the questionnaire respondents. The acute toxicities were mild, and no acute grade 3-4 toxicity was noted. Wound infection was noted in two patients (4.5%). There was only one event of regional lymph node recurrence in one patient. The 3-year LRFS, DMFS, and OS were 100%, and RRFS was 94.7%. For two patients who had a positive lymph node based on their final pathology reports, postoperative irradiation, including whole breast and regional lymph nodes, was added. CONCLUSION: Accelerated partial breast irradiation using interstitial brachytherapy with the intraoperative free-hand catheter implantation technique provides an alternative method of postoperative radiotherapy for selected patients with early breast cancer after BCS with acceptable toxicities.

Analysis of the Pathogenicity and Phylogeny of Colletotrichum Species Associated with Brown Blight of Tea (Camellia sinensis) in Taiwan.

Brown blight, a destructive foliar disease of tea, has become a highly limiting factor for tea cultivation in Taiwan. To understand the population composition of the causal agents (Colletotrichum spp.), the fungal diversity in the main tea-growing regions all over Taiwan was surveyed from 2017 to 2019. A collection of 139 Colletotrichum isolates was obtained from 14 tea cultivars in 86 tea plantations. Phylogenic analysis using the ribosomal internal transcribed spacer, glutamine synthetase gene, Apn2-Mat1-2 intergenic spacer, ß-tubulin, actin, calmodulin, and glyceraldehyde-3-phosphate dehydrogenase genes together with morphological characterization revealed three species associated with brown blight of tea; namely, Colletotrichum camelliae (95.6% of all isolates), C. fructicola (3.7%), and C. aenigma (0.7%). This is the first report of C. aenigma in Taiwan. The optimal growth temperatures were 25°C for C. camelliae and 25 and 30°C for C. fructicola and C. aenigma. Although C. fructicola and C. aenigma were more adapted to high temperature, C. camelliae was the most pathogenic across different temperatures. Regardless of whether spore suspensions or mycelial discs were used, significantly larger lesions and higher disease incidences were observed for wounded than for nonwounded inoculation and for the third and fourth leaves than for the fifth leaves. Wounded inoculation of detached third and fourth tea leaves with mycelial discs was found to be a reliable and efficient method for assessing the pathogenicity of Colletotrichum spp. within 4 days. Preventive application of fungicides or biocontrol agents immediately after tea pruning and at a young leaf stage would help control the disease.

Pontisma blauvikense sp. nov. the first member of the early-diverging oomycete genus Pontisma parasitizing brown algae.

Holocarpic oomycetes have been neglected over several decades, until interest in these organisms has recently resurged. One of the most widespread genera of holocarpic oomycetes is Pontisma, parasitic to red seaweeds throughout all oceans. Recently, the genus Sirolpidium (parasitic to green algae) was found to be congeneric with Pontisma. This hinted at a high pathogenic versatility and prompted the screening of other macroalgae on the coastline of Iceland. During this survey a parasite of the brown algae Pylaiella littoralis was found, which formed anisolpidium-like thalli, but produced biflagellate zoospores. Phylogenetic investigations revealed that the parasite was placed in the genus Pontisma. In reconstructions based on partial nrSSU sequences, it grouped with some sequences of parasitoids of the diatom genus Licmophora, but the more variable mitochondrial cox2 sequences were divergent. Based on phylogenetic evidence and the unique parasitism of brown algae, the parasitoid is described as Pontisma blauvikense in this study. Pontisma blauvikense is the fourth oomycete species parasitic to Pylaiella, which is also parasitised by Euychasma dicksonii and two Anisolpidium species. For a better understanding of the ecology and evolution of holocarpic oomycetes, further research is necessary to investigate the host spectrum of Pontisma in general and Pontisma blauvikense in particular.

Retroperitoneal laparoscopic adrenalectomy for large adrenal tumors-analysis of tumor size and adverse events: a retrospective single-center study.

Introduction: Adrenal tumors are relatively common, and adrenalectomy is the third most common endocrine surgery. Patients with adrenal tumors were categorized into two groups for analysis: those with intermediate (4-6 cm, Group 1) and large (>6 cm, Group 2) tumors undergoing Retroperitoneal Laparoscopic Adrenalectomy (RLA). The primary outcome is to compare the surgical outcomes between these two groups. The secondary outcome involves analyzing the relationship between tumor characteristics and the incidence of adverse events. Methods: Data from 76 patients who underwent RLA for tumors of size ≥4 cm between 2005 and 2022 at a single tertiary referral center were analyzed retrospectively. Variables, including patients' age, hormone function, operation time, conversion to open approach, perioperative complications, and adverse surgical events (blood loss >500 cc, conversion to open approach, and perioperative complications), were assessed. Results: No significant differences were observed between the two groups in terms of functional and histopathologic analysis, gender distribution, functioning factors, perioperative complications, and estimated blood loss. However, patients in Group 2 were younger (median age 50, IQR: 40-57, P = 0.04), experienced longer operative times (median 175 min, IQR: 145-230 min, P = 0.005), and had a higher rate of conversion to open surgery (12%, P = 0.033). For every 1 cm increase in tumor size, the odds ratio for adverse surgical events increased by 1.58. Conclusions: RLA is a safe and feasible procedure for adrenal tumors larger than 6 cm. While intraoperative and postoperative complications are not significantly increased in either group, larger tumors increase surgery times and are more likely to require conversion to open surgery. Therefore, caution and preparedness for potential adverse events are recommended when dealing with larger tumors. A tumor size of 5.3 cm may serve as a guide for risk stratification and surgical planning in large adrenal tumor management.

Comparison of overall survival after neoadjuvant and adjuvant chemotherapy in patients with early breast cancer with immediate breast reconstruction after mastectomy: A retrospective, matched case-control study.

Immediate breast reconstruction after mastectomy combined with chemotherapy is the preferred option for patients with early-stage breast cancer who require both superior clinical and aesthetic outcomes. The present study aimed to determine the survival benefits of neoadjuvant and adjuvant chemotherapy for patients with early-stage breast cancer who have undergone immediate breast reconstruction after mastectomy in Taiwan. The present study compared overall survival (OS) following neoadjuvant or adjuvant chemotherapy in 139 patients with early-stage breast cancer who underwent immediate breast reconstruction after mastectomy. Patient data were used retrospectively as an unmatched cohort. Next, 37 neoadjuvant cases were matched with 37 adjuvant controls through 1:1 age-, clinical stage-, and molecular subtype-matching. OS differences between the cases and controls were determined using Kaplan-Meier survival curve analyses. Here, 77.7 and 81.1% of the unmatched and matched cohort patients were aged <50 years, respectively. Of the matched neoadjuvant cases, 10 (15.6%) reached pathologic complete response after neoadjuvant chemotherapy, whereas 5 (13.5%) neoadjuvant cases succumbed during the study period. The neoadjuvant matched cases demonstrated a significantly poor OS with their adjuvant matched controls (P=0.044); nevertheless, the stratification analysis results demonstrated that the survival differences between the neoadjuvant and the adjuvant controls decreased after matching. Targeted therapy demonstrated the same OS benefits for both the neoadjuvant matched cases and adjuvant matched controls (P=1.000). This study provided matched case-control evidence for the feasibility of neoadjuvant chemotherapy combined with targeted therapy for patients with early-stage breast cancer with immediate breast reconstruction after mastectomy in a Taiwanese female population.

Impact of sarcopenia on the prognosis and treatment of lung cancer: an umbrella review.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality worldwide. Sarcopenia, defined as the loss of muscle mass and function, is known to cause adverse health outcomes. The purpose of this umbrella review was to integrate published systematic reviews and meta-analyses exploring sarcopenia and lung cancer to provide comprehensive knowledge on their relationship. METHODS: Eligible studies were searched from scientific databases until June 28, 2022. Critical appraisal was performed using A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. The impact of sarcopenia on the pathophysiology, prevalence, and prognosis of lung cancer is summarized at the level of systematic reviews or meta-analyses. RESULTS: Fourteen reviews and meta-analyses were conducted. The methodological quality was high for one review, low for nine, and critically low for four. The most common standard for diagnosing sarcopenia in the lung cancer population is computed tomography (CT) to measure the skeletal muscle index at the third lumbar vertebra (L3). Sarcopenia was highly prevalent among patients with lung cancer, with a pooled prevalence ranging from 42.8% to 45.0%. The association between sarcopenia and increased postoperative complications and decreased disease control rates with immune checkpoint inhibitors has been demonstrated. Mortality was significantly higher in sarcopenic patients than in non-sarcopenic patients with lung cancer, regardless of the stage of disease or type of treatment. CONCLUSIONS: Sarcopenia is a poor prognostic factor for lung cancer. Future studies are necessary to clarify the pathophysiology of sarcopenia and develop effective interventions for sarcopenia in patients with lung cancer.

Effectiveness of Coenzyme Q10 Supplementation for Reducing Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Coenzyme Q10 (CoQ10) is a popular nutritional supplement, an antioxidant and an essential component of the mitochondrial electron transport chain. Several clinical studies have suggested that fatigue can be reduced by antioxidant supplementation. However, the data on this topic has been sparse to date. Hence, we conducted this meta-analysis with the aim of investigating the effectiveness of fatigue reduction via CoQ10 supplementation. More specifically, we searched electronic databases for randomized controlled trials (RCTs) published from the database inception to January 2022. A random effects model was implemented to conduct the meta-analysis among 13 RCTs (with a total of 1,126 participants). As compared with the placebo groups evaluated in each RCT, the CoQ10 group showed a statistically significant reduction in fatigue scores (Hedges' g = -0.398, 95% confidence interval = -0.641 to -0.155, p = 0.001). The directions of the treatment effects were consistent between the healthy and diseased participants. Compared with the placebo group, the effect of reducing fatigue was statistically significant in the subgroup using the CoQ10-only formulation but not in the subgroup using CoQ10 compounds. The results of our meta-regression demonstrate that increases in the daily dose (coefficient = -0.0017 per mg, p < 0.001) and treatment duration (coefficient = -0.0042 per day, p = 0.007) of CoQ10 supplementation were correlated with greater fatigue reduction. There was only one adverse (gastrointestinal) event in the 602 participants who underwent the CoQ10 intervention. Based on the results of this meta-analysis, we conclude that CoQ10 is an effective and safe supplement for reducing fatigue symptoms. Systematic Review Registration: https://inplasy.com/inplasy-2022-1-0113/, identifier INPLASY202210113.

Analysis of EZH2 Genetic Variants on Triple-Negative Breast Cancer Susceptibility and Pathology.

Triple-negative breast cancer (TNBC) is the third most common female cancer in Taiwan. EZH2 plays an important role in cancer development through transcriptional repression by chromatin remodeling. However, the expression of EZH2 in breast cancer is highly correlated with tumorigenesis, and patient survival is not matched to TNBC. Furthermore, it has not been determined if specific EZH2 genetic variants are associated with breast cancer risk. In this paper, we evaluated the survival of different types of breast cancer. The results indicated that a lower expression of EZH2 led to poor survival of TNBC patients. Therefore, we aimed at studying the relationship between genetic polymorphisms of EZH2 and susceptibility to TNBC in Taiwan. Four single-nucleotide polymorphisms (SNPs) of EZH2 (rs6950683, rs2302427, rs3757441, and rs41277434) were analyzed by real-time PCR genotyping in 176 patients with TNBC and 1000 cancer-free controls. The results showed that TNBC patients under 60 years old who carried a TC or CC genotype at EZH2 rs6950683 and re3757441 had a tumor size of 20 mm or smaller (T1). Thus, this study is the first to examine the age and mutant genes associated with EZH2 SNPs in TNBC progression and development in Taiwan.

Does suprascapular nerve release provide additional benefits for rotator cuff repair: a systematic review and meta-analysis.

BACKGROUND: There is still a lack of consensus regarding whether suprascapular nerve decompression should be routinely performed with rotator cuff repair. Therefore, this meta-analysis aimed to evaluate whether additional suprascapular nerve release (SSNR) could improve shoulder functional outcomes and pain relief more than rotator cuff repair alone. MATERIALS AND METHODS: We performed a literature review of electronic databases for noncomparative and comparative studies investigating the effect of SSNR in patients undergoing rotator cuff repair. The primary outcome was the change in shoulder function scores from the preoperative status, and the secondary outcome was the change in the visual analog scale (VAS) score of pain after surgery. A subgroup analysis was conducted based on the study design (noncomparative studies vs. comparative studies). RESULTS: Nine studies comprising 279 participants were included. Our analysis demonstrated that the group that underwent SSNR had a better shoulder functional score after surgery than at preoperative assessment (standardized mean difference [SMD], 1.333, 95% confidence interval [CI], 0.708-1.959). No significant differences were identified in shoulder function improvement between those with and without SSNR, with an SMD of 0.163 (95% CI, -0.091 to 0.418). Likewise, the group with SSNR showed a decreased VAS score after surgery compared to their preoperative status (SMD, 0.910; 95% CI, 0.560-1.260). However, there was no significant difference in VAS change between those with and without SSNR, with an SMD of 0.431 (95% CI, -0.095 to 0.956). CONCLUSION: The present meta-analysis revealed that SSNR might not be routinely needed in rotator cuff tendon repair as no additional benefits in functional improvement or pain relief were identified compared to rotator cuff tendon repair alone.

Clinical Outcomes of Neoadjuvant Therapy in Human Epidermal Growth Factor Receptor 2 Breast Cancer Patients: A Single-Center Retrospective Study.

(1) Background: Neoadjuvant therapy is widely used to treat locally advanced breast cancer. It has been recently shown that it can also improve the prognosis of patients during the early stages of breast cancer. In the past, advanced breast cancer with positive Human Epidermal growth factor Receptor 2 (HER2+) resulted in poor prognoses; however, outcomes have since changed after the introduction of HER2-targeting therapy. Achieving pathological Complete Response (pCR) is the most important aim, as it is a predictor of long-term outcomes in high-risk breast cancer subtypes. (2) Methods: We performed a retrospective review of all breast cancer patients who were treated with neoadjuvant therapy at Taichung Veterans General Hospital (VGHTC) between 2010 and 2018. A total of 147 HER2+ breast cancer patients who underwent neoadjuvant chemotherapy involving anthracycline and taxane-based regimens were enrolled. Within that population, 95 and 52 cases received single-blockade (Trastuzumab) and dual-blockade (Trastuzumab and Pertuzumab) neoadjuvant anti-HER2 therapy, respectively. (3) Results: The dual-blockade therapy group displayed a significantly higher pCR rate after surgery as compared to the single-blockade group (63.5% vs. 43.2%, p = 0.019). Advanced stage, larger tumor size, lymph node involvement and HER2 expression status were associated with the pCR rate. The 4-year OS was 85.2% and 100% in the single-blockage and dual-blockade therapy groups, respectively (p = 0.041). (4) Conclusion: Anthracycline, followed by taxane-based neoadjuvant chemotherapy combined with the dual HER2-blockade, had a higher pCR rate and better outcome when compared with the single HER2-blockade strategy in locally advanced HER2 breast cancer.

Upcycling fruit peel waste into a green reductant to reduce graphene oxide for fabricating an electrochemical sensing platform for sulfamethoxazole determination in aquatic environments.

Fruit and vegetable wastes contribute to a substantial proportion of global food waste. While these wastes could potentially be repurposed for a wide range of applications, the majority of them are discarded without effective utilization. To address the current challenges of fruit waste accumulation and sustainable nanomaterial synthesis, natural reductants derived from discarded dragon fruit (Hylocereus polyrhizus) peels are proposed as an alternative to conventional hazardous reductants for graphene-based material synthesis. Given that the chemical reduction of graphene oxide (GO) is the major route for graphene production, the effectiveness of the proposed reductants derived from peels of dragon fruit on graphene oxide reduction was evaluated. The reducing constituents (i.e., betanin substances) were recovered from dragon fruit peel wastes using facile aqueous extraction processes, where suitable extraction treatments (e.g., pH conditions) were found to be critical for boosting the reducing power of the obtained reductants. The compiled results indicated that the proposed fruit waste-derived reducing agents demonstrated great promise for GO reduction through SN2 nucleophilic reactions, mainly driven by the extracted betanin. The obtained reduced GO serves as a promising platform for electrochemical determination of sulfamethoxazole in aquatic environments, realizing both food waste valorization and environmentally benign material synthesis.

The Effect of Curcumin Differs on Individual Cognitive Domains across Different Patient Populations: A Systematic Review and Meta-Analysis.

Curcumin is a polyphenol with strong antioxidant and anti-inflammatory effects that has been shown to be effective in ameliorating cognitive decline in animal studies. However, its clinical effectiveness is inconclusive, and relevant gastrointestinal adverse events (AEs) have been reported. The aim of this meta-analysis was to summarize the existing evidence from randomized controlled trials (RCTs) of effects of curcumin on overall cognitive function, individual cognitive domains, and gastrointestinal AE. The study includes 8 RCTs and 389 participants. A random-effects model was used for the meta-analysis. Compared with the placebo group, the curcumin group was associated with an improvement in working memory (Hedges' g = 0.396, 95% confidence interval (CI) = 0.078 to 0.714, p = 0.015) and a borderline benefit in processing speed (Hedges' g = 0.303, 95% CI = -0.013 to 0.619, p = 0.06). In the domains of language, episodic memory/visual learning, verbal memory, cognitive flexibility/problem solving, and overall cognitive function, no significant difference existed for the comparison between the curcumin and placebo groups. The curcumin group had a significantly higher risk of gastrointestinal AEs than the placebo group (odds ratio = 3.019, 95% CI = 1.118 to 8.150, p = 0.029). In the future, the effects of curcumin on working memory, processing speed, and gastrointestinal AE should be further investigated.

Molecular Phylogenetic Diversity and Biological Characterization of Diaporthe Species Associated with Leaf Spots of Camellia sinensis in Taiwan.

Camellia sinensis is one of the major crops grown in Taiwan and has been widely cultivated around the island. Tea leaves are prone to various fungal infections, and leaf spot is considered one of the major diseases in Taiwan tea fields. As part of a survey on fungal species causing leaf spots on tea leaves in Taiwan, 19 fungal strains morphologically similar to the genus Diaporthe were collected. ITS (internal transcribed spacer), tef1-α (translation elongation factor 1-α), tub2 (beta-tubulin), and cal (calmodulin) gene regions were used to construct phylogenetic trees and determine the evolutionary relationships among the collected strains. In total, six Diaporthe species, including one new species, Diaporthe hsinchuensis, were identified as linked with leaf spot of C. sinensis in Taiwan based on both phenotypic characters and phylogeny. These species were further characterized in terms of their pathogenicity, temperature, and pH requirements under laboratory conditions. Diaporthe tulliensis, D. passiflorae, and D. perseae were isolated from C. sinensis for the first time. Furthermore, pathogenicity tests revealed that, with wound inoculation, only D. hongkongensis was pathogenic on tea leaves. This investigation delivers the first assessment of Diaporthe taxa related to leaf spots on tea in Taiwan.

Stemphylium Leaf Blight of Welsh Onion (Allium fistulosum): An Emerging Disease in Sanxing, Taiwan.

Welsh onion (Allium fistulosum L.) is one of the main and oldest vegetable crops grown in Taiwan. A severe epidemic of leaf blight in Welsh onion caused by a Stemphylium-like pathogen was found in Sanxing, Taiwan, from 2018 to 2020. However, correct species identification, biology, and control of Stemphylium leaf blight (SLB) of Welsh onion are not well-established. Therefore, the main objective of this study was to investigate the causal agent of SLB in Sanxing and evaluate the in vitro sensitivity of Stemphylium-like pathogen to commonly used fungicides. A phylogenetic analysis based on combining the internal transcribed spacer (ITS) region and glyceraldedyhe-3-phosphate dehydrogenase (gapdh) and calmodulin (cmdA) gene sequences together with morphological features identified that S. vesicarium is associated with SLB in Sanxing. When inoculated onto Welsh onion leaves, the isolates caused symptoms identical to those observed in the field; therefore, S. vesicarium was reisolated and Koch's postulates were confirmed. We observed a higher incidence of SLB symptoms on the oldest leaves compared with younger leaves. The maximum and minimum temperatures for in vitro mycelial growth and conidial germination (%) of S. vesicarium were 20 to 30°C and 5°C, respectively. Sixteen fungicides were tested for their effectiveness to reduce the mycelial growth and conidial germination of S. vesicarium in vitro. Boscalid plus pyraclostrobin, fluopyram, fluxapyroxad, and fluxapyroxad plus pyraclostrobin were highly effective at reducing mycelial growth and conidial germination in S. vesicarium. However, strobilurin fungicides (azoxystrobin and kresoxim-methyl) commonly used in Welsh onion production in Sanxing were ineffective. This study discusses the emergence of SLB caused by S. vesicarium in the foliar disease complex affecting Welsh onion and the management of the disease using fungicides with different modes of action in Taiwan. The research will support the sustainable management of SLB in Sanxing, Taiwan; however, further field assessments of the fungicides are warranted.

Capsanthin induces G1/S phase arrest, erlotinib-sensitivity and inhibits tumor progression by suppressing EZH2-mediated epigenetically silencing of p21 in triple-negative breast cancer cells.

Capsanthin is a naturally occurring red pepper carotenoid with possible antitumor activity, but its antitumor mechanisms have yet to be delineated. We tested the anti-proliferative activity of capsanthin with human triple-negative breast cancer (TNBC) and found that cell proliferation was inhibited after 24, 48 and 72 h of treatment. We also investigated the cellular and molecular mechanisms of the antitumor efficacy of capsanthin on TNBC cells and found that capsanthin delayed cell-cycle progression at the G1/S stage, that cyclin A expression was suppressed, and that p21 expression was upregulated. Capsanthin also inhibited the EZH2 expression and EZH2 could binding to the p21 promoter in TNBC cells. We further discovered that capsanthin has synthetic effects when combined with erlotinib (Tarceva). In the animal experiment, we found that the capsanthin-induced inhibition of TNBC cell proliferation decreased the incidence of the initiation and growth of TNBC cell-derived tumors in mice. Our study reveals that capsanthin exerted antitumor effects through delaying cell-cycle progression, induces erlotinib-sensitivity and inhibits tumor progression by inhibiting EZH2/p21 axis, and capsanthin is a potential drug candidate for development of a safe and effective therapy against TNBCs, especially for TNBCs that have developed resistance to targeting therapy.

Efficacy Of Pegylated Liposomal Doxorubicin-based Neoadjuvant Chemotherapy In Breast Cancer: A Single Center Experience.

PURPOSE: Neoadjuvant chemotherapy using a doxorubicin-based regimen has recently become a common therapeutic option for operable breast cancer. This study aimed to investigate the efficacy of polyethylene glycol-coated liposomal doxorubicin (PLD)-based chemotherapy for breast cancer in neoadjuvant settings. METHODS: A total of 227 female operable breast cancer patients who were diagnosed between January 2009 and December 2017 and completed neoadjuvant PLD-based chemotherapy were retrospectively included. The logistic regression analysis was used to determine the associations between pathologic complete response (pCR) and preoperative clinicopathological characteristics. The breast cancer recurrence rate was estimated using the survival analysis. RESULTS: A higher pCR rate was found in the patients with clinically negative lymph nodes and HER2-enriched patients. Moreover, the patients who achieved pCR also had a better prognosis outcome. A recurrence rate of 11.5% (n=26) was observed during a median follow-up of 11.63 months, and the recurrence rate of the pCR group (2.04%; 95% CI = 0.29-13.62) was lower than the non-pCR group (14.62%; 95% CI = 10.12-20.87). Higher histological grade was also associated high pCR rate (52.0% vs 40.0%). CONCLUSION: The use of PLD-containing chemotherapeutics in neoadjuvant settings might have benefits for non-metastatic operable breast cancer in Taiwanese females.