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1.
Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3-ITD: A multicenter phase 2 study.
Yu, S, Zhang, Y, Yu, G, Wang, Y, Shao, R, Du, X, Xu, N, Lin, D, Zhao, W, Zhang, X, et al
Journal of internal medicine. 2024;(2):216-228
Abstract
BACKGROUND Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3-internal tandem duplication (FLT3-ITD) respond infrequently to salvage chemotherapy. OBJECTIVE To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population. METHODS This multicenter, single-arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML with FLT3-ITD (aged 18-65 years) who were treated with VAH. The primary endpoint was composite complete remission (CRc) after two cycles. Secondary outcomes included the overall response rate (ORR), safety, and survival. RESULTS Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom were enrolled. The median patient age was 47 years (interquartile range [IQR] 31-57). CRc was 76.5% with ORR of 82.4%. At a median follow-up of 17.7 months (IQR, 8.7-24.7), the median duration of CRc was not reached (NR), overall survival was 18.1 months (95% confidence interval [CI], 11.8-NR) and event-free survival was 11.4 months (95% CI, 5.6-NR). Grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92.2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%), and sepsis in 6 (11.8%) patients. Treatment-related death occurred in two (3.9%) patients. CONCLUSIONS The sorafenib plus VAH regimen was well tolerated and highly active against R/R AML with FLT3-ITD. This regimen may be a suitable therapeutic option for this population, but larger population trials are needed to be explored. TRIAL REGISTRATION Clinical Trials Registry: NCT04424147.
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2.
Clinical and ocular abnormalities in DEGCAGS syndrome-Developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities.
Ali, SM, AlMasri, DA, Prada, CE, Lin, D, Bosley, TM, Kozak, I
Molecular genetics & genomic medicine. 2024;(1):e2329
Abstract
PURPOSE To describe clinical and ocular abnormalities in a case of Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities (DEGCAGS syndrome). METHODS A clinical report. CASE DESCRIPTION An infant born to a consanguineous Middle Eastern family who was delivered by cesarean section because of in utero growth restriction, premature labor, and breech presentation. Post-partum medical problems included hypotension, generalized hypotonia, bradycardia, apnea requiring resuscitation and positive pressure ventilation, facial dysmorphia, skeletal malformations, and disorders of the gastrointestinal, immune, urinary, respiratory, cardiac, and visual systems. The family reported that a previous child had severe hypotonia at birth and was given the diagnosis of hypoxic ischemic encephalopathy; that child remains on a ventilator in a chronic care facility. Our patient was found to be homozygous for a novel pathogenic missense variant in theZNF699 zinc finger gene on chromosome 19p13 causing a syndrome known as Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities (DEGCAGS syndrome). We review this variable syndrome, including abnormalities of the visual system not described previously. CONCLUSIONS We describe the 15th child to be presumably identified with the DEGCAGS syndrome and the first individual with homozygous missense variants in the ZNF699 gene who had complete clinical examination and detailed retinal imaging.
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3.
Developing Ganoderma lucidum as a next-generation cell factory for food and nutraceuticals.
Azi, F, Wang, Z, Chen, W, Lin, D, Xu, P
Trends in biotechnology. 2024;(2):197-211
Abstract
Ganoderma lucidum holds a colossal reservoir of hydrolytic enzymes and therapeutic compounds and can be a sustainable source of proteins and bioactive compounds. Its metabolic versatility, propelled by its rich genome content, provides excellent biosynthetic machinery for innovation-driven pathway engineering. However, robust regulatory networks and low frequency of homologous recombination are critical bottlenecks that limit the development of molecular tools and precise genetic markers for biomanufacturing innovations in this organism. Modern synthetic biology provides tools that could help to accelerate precise multiple gene targeting and editing and untangling the biosynthetic machinery of G. lucidum. This review provides insight into molecular strategies to unwind the regulatory bottlenecks and transform G. lucidum into efficient cell factories for food and nutraceuticals.
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4.
Epidermal microorganisms contributed to the toxic mechanism of nZVI and TCEP in earthworms by robbing metal elements and nutrients.
Hou, J, Yang, M, Wu, X, Chen, Q, Lu, Y, Zhang, J, Lin, D
Eco-Environment & Health. 2024;(1):80-88
Abstract
Disrupting effects of pollutants on symbiotic microbiota have been regarded as an important mechanism of host toxicity, with most current research focusing on the intestinal microbiota. In fact, the epidermal microbiota, which participates in the nutrient exchange between hosts and environments, could play a crucial role in host toxicity via community changes. To compare the contributions of intestinal and epidermal symbiotic microorganisms to host toxicity, this study designed single and combined scenarios of soil contamination [nano zero-valent iron (nZVI) and tris (2-chloroethyl) phosphate (TCEP)], and revealed the coupling mechanisms between intestinal/epidermal symbiotic bacterial communities and earthworm toxicological endpoints. Microbiome analysis showed that 15% of intestinal microbes were highly correlated with host endpoints, compared to 45% of epidermal microbes showing a similar correlation. Functional comparisons revealed that key species on the epidermis were mainly heterotrophic microbes with genetic abilities to utilize metal elements and carbohydrate nutrients. Further verifications demonstrated that when facing the co-contamination of nZVI and TCEP, certain symbiotic microorganisms became dominant and consumed zinc, copper, and manganese along with saccharides and amino acids, which may be responsible for the nutritional deficiencies in the host earthworms. The findings can enrich the understanding of the coupling relationship between symbiotic microorganisms and host toxicity, highlighting the importance of epidermal microorganisms in host resistance to environmental pollution.
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5.
[Effects of Polystyrene Microplastics on Growth, Physiology, Biochemistry, and Canopy Temperature Characteristics of Chinese Cabbage Pakchoi (Brassica chinensis L.)].
Guo, BL, Feng, CC, Chen, Y, Lin, D, Li, LT
Huan jing ke xue= Huanjing kexue. 2023;(9):5080-5091
Abstract
The aim of this study was to clarify the response characteristics of Chinese cabbage pakchoi (Brassica chinensis L.) under two particle size (100 nm and 1000 nm) polystyrene microplastic (PS-MPs) stress conditions. This study can provide a theoretical basis and experimental reference for the interpretation of the physiological and ecological mechanism of microplastic pollution and the bioremediation of microplastic-contaminated soil. Hydroponic experiments were carried out to study the effects of two particle sizes (100 nm and 1000 nm) of PS-MPs on growth, photosynthetic physiology, antioxidant enzyme activities, nutritional quality, anatomical structure, and canopy temperature in Chinese cabbage pakchoi. The results showed that PS-MPs stress significantly inhibited the growth and development of Chinese cabbage pakchoi. When PS-MPs stress was increased, the phenotypic indicators were significantly reduced. Meanwhile, PS-MPs stress significantly enhanced the oxidative stress response of Chinese cabbage pakchoi, such as the activities of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX) and the content of malondialdehyde (MDA) in leaves. Such a change tended to decrease the thickness of fenestrated and leaf and spongy tissues. Moreover, PS-MPs stress significantly increased the canopy population temperature of the Chinese cabbage pakchoi leaves. Microplastic stress had obvious inhibitory effects and toxic damage on the growth, development, and physical and chemical properties of Chinese cabbage pakchoi.
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6.
WISER Survivor Trial: Combined Effect of Exercise and Weight Loss Interventions on Adiponectin and Leptin Levels in Breast Cancer Survivors with Overweight or Obesity.
Lin, D, Sturgeon, KM, Gordon, BR, Brown, JC, Sears, DD, Sarwer, DB, Schmitz, KH
Nutrients. 2023;(15)
Abstract
Adipocyte dysregulation is one mechanism linking overweight and breast cancer recurrence. Exercise and weight loss are associated with a decreased risk of breast cancer recurrence in breast cancer survivors with overweight or obesity, which may be mediated through reduced leptin levels, increased adiponectin levels, and an elevated adiponectin to leptin (A:L) ratio. The four-arm randomized controlled WISER Survivor trial examined the 12-month intervention effects of exercise, weight loss, and the combination of exercise and weight loss on adipokine levels among breast cancer survivors (n = 339) with overweight or obesity. Compared with Control, the Combination of Exercise and Weight Loss decreased leptin levels (-35.9%; 95% CI: -46.8%, -25.0%) and increased A:L ratio (11.6%; 95% CI: 5.6%, 17.6%) but did not change adiponectin levels (4.1%; 95% CI: -3.1%, 11.2%). Compared with Control, Weight Loss Alone decreased leptin levels (-35.6%; 95% CI: -46.6%, -24.5%) and increased A:L ratio (10.6%; 95% CI: 4.7%, 16.5%) but did not change adiponectin levels (0.9%; 95% CI: -6.0%, 7.9%). Compared with Control, Exercise Alone did not change leptin levels, adiponectin levels, or A:L ratio. In analyses that consolidated intervention groups, compared with Control, weight loss of ≥5% decreased leptin levels (p trend < 0.01) and increased A:L ratio (p trend < 0.01) but did not alter adiponectin levels (p trend = 0.53). Weight loss, with or without exercise, was associated with decreased leptin levels in breast cancer survivors with overweight or obesity. Improvements in the adipokine secretion profile (A:L ratio) were primarily driven by a weight loss-induced change in leptin levels.
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7.
Nanocellulose: An amazing nanomaterial with diverse applications in food science.
Zhang, F, Shen, R, Li, N, Yang, X, Lin, D
Carbohydrate polymers. 2023;:120497
Abstract
Recently, nanocellulose has gained growing interests in food science due to its many advantages including its broad resource of raw materials, renewability, interface stability, high surface area, mechanical strength, prebiotic characteristics, surface chemistry versatility and easy modification. Since then, this review summarized the sources, morphology, and structure characteristics of nanocellulose. Meanwhile, the mechanical, chemical, and combined treatment methods for the preparation of nanocellulose with desired properties were elaborated. Furthermore, the application of nanocellulose in Pickering emulsions, reinforced food packaging, functional food ingredient, food-grade hydrogels, and biosensors were emphasized. Finally, the safety, challenges, and future perspectives of nanocellulose were discussed. This work provided key developments and effective benefits of nanocellulose for future research opportunities in food.
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8.
Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.
Shi, J, Shiraishi, K, Choi, J, Matsuo, K, Chen, TY, Dai, J, Hung, RJ, Chen, K, Shu, XO, Kim, YT, et al
Nature communications. 2023;(1):3043
Abstract
Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.
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9.
Effects of platelet-rich plasma on subchondral bone marrow edema and biomarkers in synovial fluid of knee osteoarthritis.
Lin, W, Xie, L, Zhou, L, Zheng, J, Zhai, W, Lin, D
The Knee. 2023;:161-169
Abstract
BACKGROUND The aim of the study was to investigate the effect of platelet-rich plasma (PRP) on subchondral bone marrow edema (BME) and the level of biomarkers in synovial fluid of the knee osteoarthritis. METHODS Eighty-one patients with symptomatic knee osteoarthritis were randomly divided into two groups according to the number of inpatients. Forty-five cases were treated with intra-articular injection of PRP (PRP group), 36 cases were treated with sodium hyaluronate (SH group), and the clinical effects were evaluated using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The changes of subchondral BME were assessed by magnetic resonance imaging (MRI) before and after treatment. The levels of TNFα, IL-6, MCP-1, MMP-1, MMP-3, and MMP-9 in synovial fluid were also detected. RESULTS All the patients completed the corresponding treatment and were followed up for 12 months without serious complications. After the treatment, the VAS and WOMAC scores of the two groups were significantly decreased, and the difference was statistically significant at different time points (P < 0.05). The VAS and WOMAC scores of the PRP group were better than those of the SH group (P < 0.05). MRI showed that the subchondral bone edema of the two groups were reduced in varying degrees, and the reduction was more noticeable in the PRP group (P < 0.05). The levels of TNFα, IL-6, MCP-1, MMP-1, MMP-3, and MMP-9 in two groups were decreased, and the difference was statistically significant at different time points (P < 0.05). However, the levels of TNFα, IL-6, MCP-1, MMP-1, MMP-3, and MMP-9 in the PRP group were significantly lower than those in the SH group (P < 0.05). CONCLUSIONS Intra-articular injection of PRP can significantly reduce the subchondral BME and the level of biomarkers in synovial fluid of the symptomatic knee osteoarthritis.
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10.
Role of breastfeeding on maternal and childhood cancers: An umbrella review of meta-analyses.
Fan, D, Xia, Q, Lin, D, Ma, Y, Rao, J, Liu, L, Tang, H, Xu, T, Li, P, Chen, G, et al
Journal of global health. 2023;:04067
Abstract
BACKGROUND Multiple studies and meta-analyses have claimed that breastfeeding is inversely correlated with maternal and childhood cancers. These results could either be causal or confounded by shared risk factors. By conducting an umbrella review, we aimed to consolidate the relationship between breastfeeding and maternal and childhood cancers. METHODS We searched PubMed, Embase, Web of Science, Elsevier ScienceDirect, and Cochrane Library databases from inception to December 2022. Two reviewers independently extracted the data and assessed the quality of the studies using standardised forms. We considered two types of breastfeeding comparisons ("ever" vs "never" breastfeeding; and "longest" vs "shortest" duration). We estimated the pooled risk and 95% confidence interval (CI) for each meta-analysis. RESULTS We included seventeen meta-analyses with 55 comparisons. There was an inverse correlation between breastfeeding and childhood leukaemia (pooled risk = 0.90, 95% CI = 0.81-0.99), neuroblastoma (pooled risk = 0.81, 95% CI = 0.71-0.93), maternal ovarian cancer (pooled risk = 0.76, CI = 0.71-0.81), breast cancer (pooled risk = 0.85, 95% CI = 0.82-0.88), and oesophageal cancer (pooled risk = 0.67, 95% CI = 0.54-0.81) for "ever" vs "never" breastfeeding; and with childhood leukaemia (pooled risk = 0.94, 95% CI = 0.89-0.98), and maternal ovarian cancer (pooled risk = 0.84, 95% CI = 0.78-0.90) and breast cancer (pooled risk = 0.92, 95% CI = 0.89-0.96) for "longest" vs "shortest" breastfeeding duration. CONCLUSIONS We found evidence that breastfeeding may reduce the risk of maternal breast cancer, ovarian cancers, and childhood leukaemia, suggesting positive implications for influencing women's decision in breastfeeding. REGISTRATION PROSPERO (CRD42021255608).