1.Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice
FU XUFENG ; HAN HANG ; YANG HONG ; XU BO ; DAI WENJIE ; LIU LING ; HE TIANTIAN ; DU XING ; PEI XIUYING
Journal of Zhejiang University. Science. B 2024;25(4):307-323,中插1-中插15
Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.
2.Frontal fibrosing alopecia
Yuqian LI ; Qilin ZHU ; Jing ZHU ; Qitao CHEN ; Zhongming LI ; Wenrong XU ; Xufeng DU ; Weixin FAN
Chinese Journal of Dermatology 2023;56(10):973-977
Frontal fibrosing alopecia is a primary lymphocytic cicatricial alopecia, and is generally considered to be a subtype of lichen planopilaris due to similar histopathological changes. Its etiology is still unclear. With the deepening of research on this disease, more and more cases of frontal fibrosing alopecia have been reported in China and other countries. This review summarizes research progress in pathogenesis, clinical and pathological characteristics, and treatment of frontal fibrosing alopecia.
3.A case of cicatricial female pattern hair loss
Zhongming LI ; Wenrong XU ; Qilin ZHU ; Jing ZHU ; Yuqian LI ; Jie SUN ; Li YIN ; Xufeng DU
Chinese Journal of Dermatology 2022;55(2):142-145
A case of cicatricial female pattern hair loss was reported. A 36-year-old female patient presented with gradually aggravated hair loss for more than 10 years. Skin examination showed diffuse hair thinning on the scalp, thin and soft hairs, and some pencil eraser-sized areas of focal atrichia. TrichoScan examination revealed markedly decreased hair density on the forehead, variability in hair diameter greater than 20%, and increased proportions of vellus hairs. Dermoscopic examination showed increased numbers of vellus hairs, plenty of focal atrichia areas measuring 3 - 5 mm in diameter, loss of some follicular ostia, and confluent white dots. Histopathological examination of vertical and transverse scalp sections showed predominantly distributed miniaturized hair follicles with lichenoid folliculitis around the infundibulum and isthmus, concentrically layered perifollicular fibrosis, a marked decrease in the number of hair follicles compared with healthy people of the same age, increased proportions of vellus hairs, a large number of miniaturized hair follicles and follicular streamers, and formation of follicular micro-scars. The patient was diagnosed with cicatricial female pattern hair loss. She received topical treatment with 5% minoxidil liniment once a day, and alternate treatment with topical tacrolimus ointment and clobetasol propionate ointment, as well as oral spironolactone at a dose of 20 mg twice a day and compound glycyrrhizin capsules at a dose of 50 mg thrice a day. After half a year of treatment, there was no marked aggravation of hair loss, and the follow-up continued.
4.A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells.
Xing DU ; Jingjing ZHANG ; Ling LIU ; Bo XU ; Hang HAN ; Wenjie DAI ; Xiuying PEI ; Xufeng FU ; Shaozhang HOU
Journal of Zhejiang University. Science. B 2022;23(4):286-299
Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extract from the fruits of the traditional Chinese herb, L. barbarum. LBP is a promising anticancer drug, due to its high activity and low toxicity. Although it has anticancer properties, its mechanisms of action have not been fully established. Ferroptosis, which is a novel anticancer strategy, is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species (ROS) accumulation. In this study, human breast cancer cells (Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast-231 (MDA-MB-231)) were treated with LBP. LBP inhibited their viability and proliferation in association with high levels of ferroptosis. Therefore, we aimed to ascertain whether LBP reduced cell viability through ferroptosis. We found that the structure and function of mitochondria, lipid peroxidation, and expression of solute carrier family 7 member 11 (SLC7A11, also known as xCT, the light-chain subunit of cystine/glutamate antiporter system Xc-) and glutathione peroxidase 4 (GPX4) were altered by LBP. Moreover, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione (GSH) production, accumulation of intracellular free divalent iron ions and malondialdehyde (MDA), and down-regulation of the expression of xCT and GPX4. Erastin (xCT inhibitor) and RSL3 (GPX4 inhibitor) inhibited the expression of xCT and GPX4, respectively, which was lower after the co-treatment of LBP with Erastin and RSL3. These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the xCT/GPX4 pathway. Therefore, LBP exhibits novel anticancer properties by triggering ferroptosis, and may be a potential therapeutic option for breast cancer.
Breast Neoplasms/drug therapy*
;
Drugs, Chinese Herbal/pharmacology*
;
Female
;
Ferroptosis
;
Glutathione/metabolism*
;
Humans
;
Iron/metabolism*
5.Biomechanical Environment Regulates Biomimetic Mineralization of Bone Matrix
Chunyang MA ; Tianming DU ; Xufeng NIU ; Yubo FAN
Journal of Medical Biomechanics 2022;37(2):E200-E210
Bone defects have always been an important cause of threat to human health, and artificial biomimetic bone repair replacement materials are currently one of the most effective and feasible solution approaches to treat bone damage. To develop artificial bone biomimetic materials, an in vitro biomimetic mineralization system must be constructed first to study in vitro biomimetic mineralization mechanism of natural bone matrix. Collagen is a template for mineralization, and its properties such as crosslinking degree, diameter, osmotic pressure, and surface charge can all directly affect mineralization progress. The biochemical and mechanical environments in which mineralization occurs are also quite distinct in their effects on mineralization process, particularly noncollagenous proteins and fluid shear stress (FSS). FSS is considered to be the main mechanical stimulation of bone tissues in micro-environment, which is of great significance to bone growth, repair and health maintenance. FSS at different levels and loading regimes has significant effects on transformation of amorphous calcium phosphate to bone apatite, self-assembly and directional alignment of collagen fibrils, and formation of hierarchical intrafibrillar mineralization. In this paper, the factors affecting collagen mineralization and their mechanism were summarized, with focus on regulation of FSS on collagen mineralization, and development direction in future was also prospected.
6.Analysis on research status and hot spots of gabapentinoid drugs in the treatment of pain
Xiaojing LU ; Xiangfen SHI ; Fangying SI ; Yuanxia ZHAO ; Jinyuan XING ; Xufeng ZHANG ; Xiaoyu ZHAO ; Shuzhang DU
China Pharmacy 2022;33(8):996-1002
OBJECTIVE To analyze the si tuation and hot spots of gabapentinoid drugs in the treatment of pain. METHODS Related researches about gabapentinoid drugs in the treatment of pain were retrieved from Web of Science core collection database during Jan. 1st,2011-Dec. 31st,2020. VOSviewer 1.6.17,CiteSpace 5.8.R1 and Excel 2018 software were used to statistically analyze the key characteristics of relevant literature ,such as the annual publications ,countries/regions,institutions,authors, journals and research hot spots. RESULTS & CONCLUSIONS A total of 3 519 literatures were retrieved ,and the annual publication outputs showed an upward trend generally. Totally 86 countries/regions had conducted relevant studies ,of which the United States ranked first (up to 1 219),and had close cooperation with the United Kingdom ,Canada,China,Germany,Japan, etc;a total of 3 996 institutions had published relevant literatures ,and the Pfizer Inc. issued the most publications ;the most studies were devoted by Professor Parsons from the University of California San Diego ,and the highest co-citations author was Professor Gilron from the Queen ’s University. Among 1 185 journals,Pain ranked first not only in the high-productive journal ,but also in the co-cited journal. The main hot topics include abuse and misuse of gabapentinoid ,off-label use of gabapentinoid ,clinical application of gabapentinoid as a component of multimodal analgesia ,and the update of guidelines for pain based on systematic evaluation and meta-analysis.
7.A proteomic analysis of Bcl-2 regulation of cell cycle arrest: insight into the mechanisms.
Xing DU ; Jingjing XIAO ; Xufeng FU ; Bo XU ; Hang HAN ; Yin WANG ; Xiuying PEI
Journal of Zhejiang University. Science. B 2021;22(10):839-855
B cell lymphoma 2 (
8.Fibrosing alopecia in a pattern distribution: a case report
Zhongming LI ; Wenrong XU ; Qilin ZHU ; Jing ZHU ; Jie SUN ; Li YIN ; Yuqian LI ; Anyi PENG ; Xufeng DU ; M. Dirk ELSTON
Chinese Journal of Dermatology 2020;53(5):356-359
A case of fibrosing alopecia in a pattern distribution (FAPD) and its clinicopathological, dermoscopic and TrichoScan features were reported to improve the understanding of FAPD. A 23-year-old male patient presented with progressive hair loss on the forehead and top of the head for 10 years, local hair thinning and softening, and occasional scalp itching. Skin examination showed diffuse sparseness of hair from the forehead to the top of the head, frontal hairline recession, focal thinning and softening of hair, some follicular keratotic papules and perifollicular erythema on the alopecic area, with no obvious scales. TrichoScan examination revealed markedly decreased hair density and increased proportions of vellus hairs. Dermoscopy showed loss of some follicular ostia and confluent white dots. Histopathological examination of the scalp showed lichenoid lymphocytic infiltration around the infundibulum and isthmus of hair follicles, concentrically layered perifollicular fibrosis, hair follicle destruction, formation of follicular micro-scars, markedly increased variation in the diameter of residual follicles, and some vellus hairs. The patient was diagnosed with FAPD. FAPD is easily misdiagnosed as androgenetic alopecia, and early diagnosis and treatment are needed.
9. Diagnostic performance of modified Ho-Vert technique in 21 cases of classical lichen planopilaris: a clinicopathological study
Zhongming LI ; Wenrong XU ; Yuqian LI ; Qilin ZHU ; Jing ZHU ; Yuanbo HUANG ; Jie SUN ; Xufeng DU ; Weixin FAN
Chinese Journal of Dermatology 2020;53(1):17-22
Objective:
To compare diagnostic performance of traditional vertical section technique, horizontal section technique and modified Ho-Vert technique for classical lichen planopilaris.
Methods:
Clinical data were collected from patients with classical lichen planopilaris in Department of Dermatology, The Affiliated Wuxi People′s Hospital of Nanjing Medical University from January 1st 2015 to January 1st 2019. With the help of dermoscopy, 2 scalp specimens were obtained from each patient and sliced horizontally and vertically respectively by using modified Ho-Vert technique. The horizontal and vertical sections were read separately or simultaneously, and histopathological changes were observed.
Results:
Totally, 21 patients with classical lichen planopilaris were enrolled into this study, including 15 males and 6 females. Their age was 50.0 ± 13.6 years, and the average course of disease was 18 months. The patients mainly presented with multifocal or confluent patchy hair loss, and scalp atrophy, perifollicular hyperkeratosis, loss of follicular ostia, fibrous white dots and orbit sign were observed. On the horizontal sections, lichenoid lymphocytic infiltration around the infundibulum and isthmus of hair follicles and follicular micro-scars could be observed in all patients, and the dermo-epidermal interface could be seen in 7 patients. On the vertical sections, lichenoid lymphocytic infiltration around the infundibulum and isthmus of hair follicles only could be observed in 9 patients, follicular micro-scars could be seen in 4, and the dermo-epidermal interface could be observed in all patients. Moreover, the detection rates of interfollicular interface dermatitis, follicular keratotic plugs, lymphocytic infiltration around sebaceous glands, atrophy or disappearance of sebaceous glands and inflammatory infiltration around hair follicle bulbs were significantly different between the horizontal and vertical sections. In combination with clinical manifestations, 7 patients could be exactly diagnosed with lichen planopilaris according to findings from horizontal sections, and 9 could be diagnosed exactly according to findings from vertical sections, while 21 could be diagnosed exactly according to histopathological findings from both horizontal and vertical sections.
Conclusion
With the help of dermoscopy, modified Ho-Vert technique can improve the efficacy of pathological diagnosis of classical lichen planopilaris, by multidimensionally showing histopathological changes.
10.Application of scalp pathological biopsy in diagnosis and treatment of alopecia
Zhongming LI ; Nan ZHOU ; Xufeng DU ; Wenrong XU ; Lei WANG ; Jie SUN ; Jun YANG ; Weixin FAN
Chinese Journal of Dermatology 2019;52(1):67-70
Alopecia is a common disease in dermatologic clinics.The diagnosis of some hair diseases does not rely on pathological examinations,and with the development of science and technology,the role of many new non-invasive detection instruments,such as dermoscopy,hair scanners and skin CT,is increasingly valued in the diagnosis and treatment of hair diseases.However,the role of pathological examination is still irreplaceable.Because of the particularity of hair diseases,hair pathology differs from common skin pathology in the aspects of scalp biopsy sites,biopsy methods and techniques,tissue-slicing methods and pathological report content.This review systematically discusses the role of scalp pathological biopsy in the diagnosis and treatment of alopecia.

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