Frigid Zone Medicine

Dissecting pathophysiology of a human dominantly inherited disease, familial amyloidotic polyneuropathy, by using genetically engineered mice

Zhenghua Li, Kenichi Yamamura

2022, 2(2): 65-75. doi: 10.2478/fzm-2022-0009

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Abstract:
Familial amyloidotic polyneuropathy (FAP) is a type of systemic amyloidosis characterized by peripheral and autonomic neuropathy. Although FAP is a typical autosomal dominant disorder caused by a point mutation in the TTR gene, the average age at onset varies significantly among different countries. This discrepancy clearly suggests that a combination of intrinsic factors as well as extrinsic (environmental) factors shapes the development of FAP. However, these factors are difficult to analyze in humans, because detailed pathologic tissue analysis is only possible at autopsy. Thus, mouse models have been produced and used to disentangle these factors. This review covers the mouse models produced thus far and how these models are applied to analyze intrinsic and extrinsic factors involved in disease development and to test drug efficacy.

Effect of cold on knee osteoarthritis: Recent research status

Haile Pan, Zilong Shen, Qi Chen, Rui Jiang, Yongchen Wang

2022, 2(2): 76-81. doi: 10.2478/fzm-2022-0010

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Abstract:
Osteoarthritis is a common chronic irreversible joint disease characterized by degenerative changes of articular cartilage and secondary hyper osteogeny. Knee osteoarthritis(KOA) affects not only the articular cartilage, but also the entire joint, including subchondral bone, joint capsule, synovial membrane, meniscus, ligaments, periarticular muscles, and tendons. The primary aim of treatment is to relieve symptoms, delay joint degeneration, and maximally maintain patient's quality of life. There are many risk factors contributing to the development of KOA, including climate. This review will discuss the relationship between climate in cold region and KOA and the possibility of modifying risk factors such as the environment for the prevention and treatment of KOA.

Effects of intermittent cold-exposure on culprit plaque morphology in ST-segment elevation myocardial infarction patients: a retrospective study based on optical coherence tomography

Jinxin Liu, Shaohong Fang, Shanjie Wang, Changbin Sun, Rong Sun, Hengxuan Cai, Bo Yu

2022, 2(2): 82-89. doi: 10.2478/fzm-2022-0011

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Abstract:
Objective Present study aimed to explore the effects of intermittent cold-exposure (ICE) on culprit plaque morphology in patients with STsegment elevation myocardial infarction (STEMI) in frigid zone. Methods Totally 848 STEMI patients with plaque rupture (N = 637) or plaque erosion (N = 211) were enrolled consecutively according to optical coherence tomography imaging. Data on the changes of outdoor air temperature corresponding to 24 solar terms were collected. Patients were divided into different groups according to 24 solar terms and the number of days with indoor central heating. Imaging data were measured and analyzed qualitatively and quantitatively. Statistical analysis was conducted to elucidate the possible association of the STEMI patients of different groups with plaque morphology of culprit vessel with alterations of ambient temperature. Results The incidence of both plaque rupture and plaque erosion presented trough in summer. The incidence of plaque rupture reached a peak value in early winter when outdoor air temperature dropped below 0℃ and declined with supply of central heating. Persistent cold exposure in early winter was positively and significantly associated with plaque rupture. The incidence of plaque erosion presented a peak in severe winter with outdoor air temperature dropping below -20℃ and steady supply of central heating. ICE in severe winter was positively and significantly associated with plaque with intact intima, especially in aged male or current smoking patients. The positive correlation of cold exposure with lipid size in culprit plaque in winter weakened with central heating. Conclusion ICE resulted from switching staying in between outdoor cold environment and indoor warm temperature with central heating in severe winter changed culprit plaque morphology in STEMI. Plaque rupture decreased whereas plaque erosion increased impacted by ICE. The effect of ICE on the transformation of plaque morphology might be explained by reduced lipid deposition.

A randomized retrospective clinical study on the choice between endodontic surgery and immediate implantation

Garegin Movsesyan, Edita Margaryan, Marianna Arakelyan, Mikhail Stepanov

2022, 2(2): 90-93. doi: 10.2478/fzm-2022-0012

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Abstract:
Background Periapical endodontic surgery (PES) for root amputation and tooth replacement by immediate implant placement are two possible treatment options for bone lesions in the root apex of a tooth that has previously undergone endodontic treatment. Treatment methods are performed when the effectiveness of orthograde canal revision is questionable or when such treatment cannot be performed. The effectiveness of these methods varies from study to study. Objective clinical evaluation of the efficacy of periapical endodontic surgery for root amputation and immediate implant placement with simultaneous tooth extraction in the proximate and long-term treatment. Materials and methods The study included 183 patients between the ages of 24 and 63. Patients were divided into 2 groups; group Ⅰ - endodontic surgery was performed to resect the apex of the tooth root (108 patients) and group Ⅱ - an operation to install an implant with simultaneous tooth extraction (75 patients). In group Ⅰ, in 36 cases, PES was performed in the area of the first molars and premolars, and 72 cases in the area of incisors and canines. In group Ⅱ, 75 patients received 231 implants. Results In all 108 patients of group Ⅰ in the postoperative period and within 1 month, the wounds healed without complications. In none of the 36 operated premolars and molars, there was no definitive elimination of the radiographic bone loss (Rude grade 2 and 3) after 12 months. In the area of incisors and canines, complete healing was observed only in 37.5% of cases (Ⅰ class according to Rud). In group Ⅱ, out of 184 implants installed immediately after tooth extraction, one was removed one month after implantation. In other cases, all implants were successfully integrated with the subsequent fabrication of prosthetic construction. Conclusion The complex "implant (installed in the socket of the tooth immediately after its removal) - bone - soft tissues - prosthetic construction" is stable over time in terms of functional and aesthetic parameters, preservation of bone tissue, and mucous membrane.

Challenges and improvement in management of neonates born to mothers with COVID-19 in China

Jie Yang, Zhuxiao Ren, Lingkong Zeng, Shiwen Xia, Lin Wang, Jiayu Miao, Zhe Zhao, Chuanzhong Yang, Xiuyong Cheng, Huayan Zhang, Yuanfang Zhu, Li Liu, Xirong Gao, Bin Yi, Zhenlang Lin, Wei Liu, Xiaoyu Zhou, Benqing Wu, Ling Chen, Zhankui Li, Xuefeng Zhang, Wei Lu, Lianhong Zhang, Xiao Chen, Xiaoyun Zhong, Falin Xu, Jinhui Wu, Yong Ji, Jiahua Pan, Yanxiang Chen, Carine Ronsmans, Zhichun Feng, on behalf of the Chinese Neonatologist Association

2022, 2(2): 94-102. doi: 10.2478/fzm-2022-0013

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Abstract:
Objective China was the first country suffering from the SARS-CoV-2 pandemic and one of the countries with stringent mother-neonate isolation measure implemented. Now increasing evidence suggests that coronavirus disease 2019 (COVID-19) should not be taken as an indication for formula feeding or isolation of the infant from the mother. Methods We conducted a retrospective cohort study in 44 hospitals from 14 provinces in China to investigate the management of neonates whose mothers have confirmed or suspected COVID-19. In addition, 65 members of Chinese Neonatologist Association (CNA) were invited to give their comments and suggestions on the clinical management guidelines for high-risk neonates. Results There were 121 neonates born to 118 mothers suspected with COVID-19 including 42 mothers with SARS-CoV-2 positive results and 76 mothers with SARS-CoV-2 negative results. All neonates were born by caesarean section, isolated from their mothers immediately after birth and were formula-fed. Five neonates were positive for SARSCoV-2 at initial testing between 36 and 46 h after birth. Regarding the confusion on the clinical management guidelines, 58.78% of the newborns were put into isolation, 32.22% were subject to PCR tests, and 5.16% and 2.75% received breastfeeding and vaccination, respectively. Conclusion The clinical symptoms of neonates born to mothers with confirmed SARS-CoV-2 were mild, though five neonates might have been infected in utero or during delivery. Given the favorable outcomes of neonates born to COVID-confirmed mothers, full isolation may not be warranted. Rather, separation of the mother and her newborn should be assessed on a case-by-case basis, considering local facilities and risk factors for adverse outcomes, such as prematurity and fetal distress.

Nortriterpenoids from the fruit stalk of Schisandra chinensis (Turcz.) Baill.

Yan Liu, Xiaohui Rong, Yuanhang Chang, Juan Pan, Wei Guan, Haixue Kuang, Bingyou Yang

2022, 2(2): 103-108. doi: 10.2478/fzm-2022-0014

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Abstract:
Objective The fruit stalk of Schisandra chinensis (Turcz.) Baill. (S. chinensis) has been found to contain bioactive components similar to the fruit of S. chinensis. Here, we report a recent discovery about new nortriterpenoids with a novel skeleton and anti-gastric cancer activity, which were isolated from the fruit stalk of S. chinensis. Methods The chemical components of ethyl acetate extract from 70% ethanol extract from S. chinensis fruit stalk were separated, purified, and identified by liquid chromatography methods (silica gel, ODS, HPLC) and extensive spectroscopic analyses (NMR, IR, UV, MS, CD). Results Two new nortriterpenoids, schilancitrilactone M and 25-hydroxyl schindilactone D (1 and 2), along with ten known nortriterpenoids (3-12) were isolated from the fruit stalk of S. chinensis. The isolated compounds were tested for their cytotoxic activities against MGC-803 cells, and the results showed that compounds 6-8 possessed significant activities with IC₅₀ of 9.01, 11.77, and 2.74 μmol/L, respectively. Conclusion Twelve nortriterpenoids including two new compounds were isolated from the fruit stalk of S. chinensis for the first time. Among them, compounds 6-8 showed significant anti-gastric cancer activities. We postulated that the fruit stalk of S. chinensis could be used as an anti-gastric cancer drug.

Altered expression profile of long non-coding RNAs during heart aging in mice

Xiuxiu Wang, Bingjie Hua, Meixi Yu, Shenzhen Liu, Wenya Ma, Fengzhi Ding, Qi Huang, Lai Zhang, Chongwei Bi, Ye Yuan, Mengyu Jin, Tianyi Liu, Ying Yu, Benzhi Cai, Baofeng Yang

2022, 2(2): 109-118. doi: 10.2478/fzm-2022-0015

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Abstract:
Objective Long noncoding RNAs (lncRNAs) play an important role in regulating the occurrence and development of cardiovascular diseases. However, the role of lncRNAs in heart aging remains poorly understood. The objective of this study was to identify differentially expressed lncRNAs in the heart of aging mice and elucidate the relevant regulatory pathways of cardiac aging. Materials and methods Echocardiography was used to detect the cardiac function of 18-months (aged) and 3-months (young) old C57BL/6 mice. Microarray analysis was performed to unravel the expression profiles of lncRNAs and mRNAs, and qRT-PCR to verify the highly dysregulated lncRNAs. Results Our results demonstrated that the heart function in aged mice was impaired relative to young ones. Microarray results showed that 155 lncRNAs were upregulated and 37 were downregulated, and 170 mRNAs were significantly upregulated and 44 were remarkably downregulated in aging hearts. Gene ontology analysis indicated that differentially expressed genes are mainly related to immune function, cell proliferation, copper ion response, and cellular cation homeostasis. KEGG pathway analysis showed that the differentially expressed mRNAs are related to cytokine-cytokine receptor interaction, inflammatory mediator regulation of TRP channels, and the NF-kappa B signaling pathway. Conclusion These results imply that the differentially expressed lncRNAs may regulate the development of heart aging. This study provides a new perspective on the potential effects and mechanisms of lncRNAs in heart aging.

Cryptotanshinone increases the sensitivity of liver cancer to sorafenib by inhibiting the STAT3/Snail/epithelial mesenchymal transition pathway

Zhiyu Li, Kegong Chen, Chao Cui, Yinghui Wang, Dequan Wu

2022, 2(2): 119-128. doi: 10.2478/fzm-2022-0016

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Abstract:
Objective Sorafenib resistance has been a major factor limiting its clinical use as a targeted drug in liver cancer. The present study aimed to investigate whether cryptotanshinone can enhance the sensitivity of liver cancer and reduce the resistance to sorafenib. Methods Sorafenib-resistant cells were established based on HepG2 and Huh7 cell lines. And the anti-tumor effect of sorafenib combined with cryptotanshinone on the sorafenib-resistant cells was verified by MTT, colony formation, transwell assays and tumor growth xenograft model. Moreover, the effects of the combined treatment on the expression of phosphorylated (p)-STAT3, as well as epithelial mesenchymal transition (EMT) and apoptosis related proteins of cells were evaluated by western blot analysis. Results It was identified that cryptotanshinone inhibited the viability of both HepG2 and Huh7 cells in a dose- and time-dependent manner, and decreased p-STAT3 expression rather than total STAT3 expression at a concentration of 40 ǌmol/L. In the sorafenib-resistant cells, sorafenib in combination with cryptotanshinone markedly inhibited cell viability, invasion and migration compared with sorafenib alone. In contrast, increased p-STAT3 level by colivelin led to the inhibition of the synergistic effect of cryptotanshinone and sorafenib not only on cell viability, but also on EMT and apoptosis, suggesting that cryptotanshinone and sorafenib may act by downregulating STAT3 signaling. Further, the inhibition of carcinogenicity effect was also verified in xenografted tumor models. Conclusion The present results indicated that cryptotanshinone could synergize with sorafenib to inhibit the proliferative, invasive, and migratory abilities of sorafenib-resistant cells by downregulating STAT3 signaling.

2022 Vol. 2, No. 2

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