bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility study of personalized speed adaptation method based on mental state for teleoperated robots
Authors: Zhang Teng , Zhang Xiaodong , Lu Zhufeng , Zhang Yi , Jiang Zhiming , Zhang Yingjie
Published: September 2022

The teleoperated robotic system can support humans to complete tasks in high-risk, high-precision and difficult special environments. Because this kind of special working environment is easy to cause stress, high mental workload, fatigue and other mental states of the operator, which will reduce the quality of operation and even cause safety accidents, so the mental state of the people in this system has received extensive attention. However, the existence of individual differences and mental state diversity is often ignored, so that most of the existing adjustment strategy is out of a match between mental state and adaptive decision, which cannot effectively improve operational quality and safety. Therefore, a personalized speed adaptation (PSA) method based on policy gradient reinforcement learning was proposed in this paper. It can use electroencephalogram and electro-oculogram to accurately perceive the operator’s mental state, and adjust the speed of the robot individually according to the mental state of different operators, in order to perform teleoperation tasks efficiently and safely. The experimental results showed that the PSA method learns the mapping between the mental state and the robot’s speed regulation action by means of rewards and punishments, and can adjust the speed of the robot individually according to the mental state of different operators, thereby improving the operating quality of the system. And the feasibility and superiority of this method were proved. It is worth noting that the PSA method was validated on 6 real subjects rather than a simulation model. To the best of our knowledge, the PSA method is the first implementation of online reinforcement learning control of teleoperated robots involving human subjects.
Differential synaptic mechanism underlying the neuronal modulation of prefrontal cortex, amygdala, and hippocampus in response to chronic postsurgical pain with or without cognitive deficits in rats
Authors: Li Zhen , He Zhigang , Li Zhixiao , Sun Tianning , Zhang Wencui , Xiang Hongbing
Published: September 2022

Chronic Postsurgical Pain (CPSP) is well recognized to impair cognition, particularly memory. Mounting evidence suggests anatomic and mechanistic overlap between pain and cognition on several levels. Interestingly, the drugs currently used for treating chronic pain, including opioids, gabapentin, and NMDAR (N-methyl-D-aspartate receptor) antagonists, are also known to impair cognition. So whether pain-related cognitive deficits have different synaptic mechanisms as those underlying pain remains to be elucidated. In this context, the synaptic transmission in the unsusceptible group (cognitively normal pain rats) was isolated from that in the susceptible group (cognitively compromised pain rats). It was revealed that nearly two-thirds of the CPSP rats suffered cognitive impairment. The whole-cell voltage-clamp recordings revealed that the neuronal excitability and synaptic transmission in the prefrontal cortex and amygdala neurons were enhanced in the unsusceptible group, while these parameters remained the same in the susceptible group. Moreover, the neuronal excitability and synaptic transmission in hippocampus neurons demonstrated the opposite trend. Correspondingly, the levels of synaptic transmission-related proteins demonstrated a tendency similar to that of the excitatory and inhibitory synaptic transmission. Furthermore, morphologically, the synapse ultrastructure varied in the postsynaptic density (PSD) between the CPSP rats with and without cognitive deficits. Together, these observations indicated that basal excitatory and inhibitory synaptic transmission changes were strikingly different between the CPSP rats with and without cognitive deficits.
Fluorescence quenching by high-power LEDs for highly sensitive fluorescence in situ hybridization
Authors: Tsuneoka Yousuke , Atsumi Yusuke , Makanae Aki , Yashiro Mitsuru , Funato Hiromasa
Published: September 2022

Recent technical advances have made fluorescent in situ hybridization (ISH) a pivotal method to analyze neural tissue. In a highly sensitive ISH, it is important to reduce tissue autofluorescence. We developed a photobleaching device using a light-emitting diode (LED) illuminator to quench autofluorescence in neural tissue. This device was equipped with 12 high-power LEDs (30 W per single LED) and an evaporative cooling system, and these features achieved highly efficient bleaching of autofluorescence and minimized tissue damage. Even after 60 min of photobleaching with evaporative cooling, the temperature gain of the tissue slide was suppressed almost completely. The autofluorescence of lipofuscin-like granules completely disappeared after 60 min of photobleaching, as did other background autofluorescence observed in the mouse cortex and hippocampus. In combination with the recently developed fluorescent ISH method using the hybridization chain reaction (HCR), high signal/noise ratio imaging was achieved without reduction of ISH sensitivity to visualize rare mRNA at single copy resolution by quenching autofluorescence. Photobleaching by the LED illuminator was also effective in quenching the fluorescent staining of ISH-HCR. We performed multiround ISH by repeating the cycle of HCR staining, confocal imaging, and photobleaching. In addition to the two-round ISH, fluorescent immunohistochemistry or fluorescent Nissl staining was conducted on the same tissue. This LED illuminator provides a quick and simple way to reduce autofluorescence and quench fluorescent dyes for multiround ISH with minimum tissue degradation.
Endoproteolysis of cellular prion protein by plasmin hinders propagation of prions
Authors: Mays Charles E. , Trinh Trang H. T. , Telling Glenn , Kang Hae-Eun , Ryou Chongsuk
Published: September 2022

Many questions surround the underlying mechanism for the differential metabolic processing observed for the prion protein (PrP) in healthy and prion-infected mammals. Foremost, the physiological α-cleavage of PrP interrupts a region critical for both toxicity and conversion of cellular PrP (PrPC) into its misfolded pathogenic isoform (PrPSc) by generating a glycosylphosphatidylinositol (GPI)-anchored C1 fragment. During prion diseases, alternative β-cleavage of PrP becomes prominent, producing a GPI-anchored C2 fragment with this particular region intact. It remains unexplored whether physical up-regulation of α-cleavage can inhibit disease progression. Furthermore, several pieces of evidence indicate that a disintegrin and metalloproteinase (ADAM) 10 and ADAM17 play a much smaller role in the α-cleavage of PrPC than originally believed, thus presenting the need to identify the primary protease(s) responsible. For this purpose, we characterized the ability of plasmin to perform PrP α-cleavage. Then, we conducted functional assays using protein misfolding cyclic amplification (PMCA) and prion-infected cell lines to clarify the role of plasmin-mediated α-cleavage during prion propagation. Here, we demonstrated an inhibitory role of plasmin for PrPSc formation through PrP α-cleavage that increased C1 fragments resulting in reduced prion conversion compared with non-treated PMCA and cell cultures. The reduction of prion infectious titer in the bioassay of plasmin-treated PMCA material also supported the inhibitory role of plasmin on PrPSc replication. Our results suggest that plasmin-mediated endoproteolytic cleavage of PrP may be an important event to prevent prion propagation.
Association between caloric adequacy and short-term clinical outcomes in critically ill patients using a weight-based equation: Secondary analysis of a cluster-randomized controlled trial
Authors: Lv Cheng , Jiang Xingwei , Long Yi , Liu Zirui , Lin Jiajia , Wu Cuili , Ye Xianghong , Ye Ruiling , Liu Yuxiu , Liu Man , Liu Yang , Chen Wensong , Gao Lin , Tong Zhihui , Ke Lu , Jiang Zhengying , Li Weiqin
Published: September 2022

Background

There is controversy over the optimal energy delivery in intensive care units (ICUs). In this study, we aimed to evaluate the association between different caloric adequacy assessed by a weight-based equation and short-term clinical outcomes in a cohort of critically ill patients.

Methods

This is a secondary analysis of a cluster-randomized controlled trial (N= 2,772). The energy requirement was estimated as 25 kcal/kg of body weight. The study subjects were divided into three groups according to their caloric adequacy as calculated by the mean energy delivered from days 3 to 7 of enrollment divided by the estimated energy requirements: (1) received < 70% of energy requirement (hypocaloric), (2) received 70–100% of energy requirement (normocaloric), and (3) received > 100% of energy requirement (hypercaloric). Cox proportional hazards models were used to analyze the association between caloric adequacy and 28-day mortality and time to discharge alive from the ICU.

Results

A total of 1,694 patients were included. Compared with normocaloric feeding, hypocaloric feeding significantly increased the risk of 28-day mortality (hazard ratio [HR] = 1.590, 95% confidence interval [CI]: 1.162–2.176,p= 0.004), while hypercaloric feeding did not. After controlling for potential confounders, the association remained valid (adjustedHR= 1.596, 95%CI: 1.150–2.215,p= 0.005). The caloric adequacy was not associated with time to discharge alive from the ICU in the unadjusted and the adjusted models.

Conclusion

Energy delivery below 70% of the estimated energy requirement during days 3–7 of critical illness is associated with 28-day mortality.

Clinical trial registration

[https://www.isrctn.com/ISRCTN12233792], identifier [ISRCTN12233792].
On how people deal with industrialized and non-industrialized food: A theoretical analysis
Authors: Amorim Alessandra , Laurindo João Borges , Sobral Paulo José do Amaral
Published: September 2022

“Canned, frozen, processed, ultra-processed, functional” etc. Two hundred years after the beginning of the food industry, industrialized food has evolved with many labels. Every person in the world eats and has different experiences with food that are connected to culture and social relationships which permeate our daily lives in many kinds of situations. Food evokes feelings, beliefs, desires, and moral values. For many people, food not only satisfies hunger and sustains life, but it also brings a delicious pleasure that is with their history, culture, and ancestry. Today's food industry pushes products through its marketing, which promotes a plethora of claims that have now trended proportionally with neophobic dimensions. In reality, the general public lacks objective knowledge about the complex science of modern food technology because of its low transparency, and this has resulted in the appearance of misleading ideas that can prejudice the correct analysis of food values. Given this, education about food is an urgent need. Notably, food scientists, technologists, and engineers must look at eaters through the prism of consumers who are human beings in all their rich social/anthropological diversity. The objective of this article is to explore the elemental anthropologic aspects of foods and how they can affect consumer's trust in the food industry's role.
A randomized, double-blind, placebo-controlled trial investigating the effects of an Ocimum tenuiflorum (Holy Basil) extract (HolixerTM) on stress, mood, and sleep in adults experiencing stress
Authors: Lopresti Adrian L. , Smith Stephen J. , Metse Alexandra P. , Drummond Peter D.
Published: September 2022

Background

In Ayurveda, Ocimum tenuiflorum (Holy Basil) is referred to as “the elixir of life” and is believed to promote longevity and general wellbeing. Although limited, there are clinical trials to suggest Ocimum tenuiflorum has anti-stress effects.

Purpose

Examine the effects of a standardized Ocimum tenuiflorum extract (HolixerTM) on subjective and objective measures of stress and sleep quality in adults experiencing stress.

Study design

Two-arm, parallel-group, 8-week, randomized, double-blind, placebo-controlled trial. Australian and New Zealand Clinical Trials Registry trial registration number ACTRN12621000609853.

Methods

One hundred volunteers aged 18–65 years received either 125 mg of Ocimum tenuiflorum twice daily or a placebo. Outcome measures included the Perceived Stress Scale (PSS) (primary outcome measure), Profile of Mood States, Athens Insomnia Scale (AIS), Restorative Sleep Questionnaire, and the Patient-Reported Outcomes Measurement Information System-29. Sleep quality was also assessed using a wrist-worn sleep tracker (Fitbit), and stress changes were examined by measuring between-group differences in hair cortisol and stress responses after exposure to an experiment stress procedure known as the Maastricht Acute Stress Test (MAST).

Results

Compared to the placebo, Ocimum tenuiflorum supplementation was associated with greater improvements in PSS (p = 0.003) and AIS (p = 0.025) scores; and at week 8, concentrations in hair cortisol were also lower (p = 0.025). Moreover, Ocimum tenuiflorum supplementation was associated with a buffered stress responses after exposure to the MAST as demonstrated by significantly lower concentrations in salivary cortisol (p = 0.001), salivary amylase (p = 0.001), systolic (p = 0.010) and diastolic (p = 0.025) blood pressure, and subjective stress ratings (p < 0.001). Ocimum tenuiflorum supplementation was well-tolerated with no reports of major adverse effects.

Conclusion

The results from this trial suggest that 8 weeks of supplementation with an Ocimum tenuiflorum extract (HolixerTM) may reduce objective and subjective measures of stress, and improve subjective measures of sleep quality. However, further research using gold-standard objective sleep measures will be required to substantiate the sleep-related findings.

Clinical trial registration

https://www.anzctr.org.au/ACTRN12621000609853p.aspx, identifier: ACTRN12621000609853p.
Potential antidepressant effects of a dietary supplement from the chlorella and lion's mane mushroom complex in aged SAMP8 mice
Authors: Chou Ming-Yu , Ho Jou-Hsuan , Huang Mao-Jung , Chen Ying-Ju , Yang Mei-Due , Lin Liang-Hung , Chi Ching-Hsin , Yeh Chin-Hsi , Tsao Tsui-Ying , Tzeng Jian-Kai , Hsu Rachel Jui-cheng , Huang Ping-Hsiu , Lu Wen-Chien , Li Po-Hsien , Wang Ming-Fu
Published: September 2022

Since the 1990s, the prevalence of mental illnesses, such as depression, has been increasing annually and has become a major burden on society. Due to the many side effects of antidepressant drugs, the development of a complementary therapy from natural materials is an urgent need. Therefore, this study used a complex extract of chlorella and lion's mane mushroom and evaluated its antidepressant effects. Six-month-old male senescence-accelerated mice prone-8 (SAMP8) were divided into positive control; negative control; and low, medium, and high-dose groups. All groups were treated with corticosterone (CORT) at 40 mg/Kg/day for 21- days to induce depression in the animals, and the effects of different test substances on animal behavior was observed. The positive control group was intraperitoneally injected with a tricyclic antidepressant (Fluoxetine, as tricyclic antidepressant), the control group was given ddH2O, and the test substance groups were administered test samples once daily for 21 days. The open field test (OFT) and forced swimming test (FST) were applied for behavior analyses of depression animal models. The OFT results showed that the mice in the positive control and the medium-, and high-dose groups demonstrated a significantly prolonged duration in the central area and a significantly increased travel distance. In the FST, the positive control and the medium, and high-dose groups displayed significantly reduced immobility times relative to the control group. The blood analysis results showed significant decreases in triglyceride and blood urea nitrogen levels relative to the positive control and the medium- and high-dose groups. Notably, in the positive control and the medium- and high-dose groups, brain-derived neurotrophic factor (BDNF) increase by more than in the control group. In summary, medium and high dose of extract of chlorella and lion's mane mushroom could improve depression behavior in animals and have the potential to be antidepressant health care products.
Elucidation of physicochemical properties of polysaccharides extracted from Cordyceps militaris fruiting bodies with different drying treatments and their effects on ulcerative colitis in zebrafish
Authors: Wei Yin , Du Xiao , Guo Yangbian , Chang Mingchang , Deng Bing , Liu Jingyu , Cao Jinling
Published: September 2022

Dry fruiting bodies of Cordyceps militaris (CMF) have been widely used in folk tonic foods and traditional herbal medicine in East Asia. Drying treatment serves as the last step in CMF industrial processes. In this work, the physicochemical properties of polysaccharides from C. militaris fruiting bodies (CMFPs) with hot air drying (HD), far-infrared radiation drying (ID) and vacuum freeze-drying (FD) treatments were analyzed, and their effects on ulcerative colitis (UC) were further investigated in oxazolone-induced zebrafish. The results showed that physicochemical properties of CMFP-H, CMFP-I and CMFP-F were obvious different. CMFPs could repair the intestinal mucosal barrier, inhibit ROS generation and the activities of MDA and MPO, and improve the activities of SOD, CAT, ACP, AKP and LZM. Further detection indicated that CMFPs could better improve UC via activating the MyD88/NF-κB signaling pathway in vivo. However, CMFP-H, CMFP-F and CMFP-I exhibited diverse regulation effects on specific immune-related enzymes and cytokines. The data would be helpful for finding practical and rapid drying methods for macro-fungi and further exploring CMFPs as functional food ingredients or complementary medicines for the treatments of UC.
Association of circulating branched-chain amino acids with risk of moyamoya disease
Authors: Zeng Chaofan , Ge Peicong , Liu Chenglong , Yu Xiaofan , Zhai Yuanren , Liu Wei , He Qiheng , Li Junsheng , Liu Xingju , Wang Jia , Ye Xun , Zhang Qian , Wang Rong , Zhang Yan , Zhao Jizong , Zhang Dong
Published: September 2022

Objective

Branched-Chain Amino Acids (BCAAs) has been identified as a risk factor for circulatory disease. Nevertheless, the effects and mechanisms of BCAAs on the risk of moyamoya disease (MMD) remain unrecognized. Hence, we aimed to elucidate the association between circulating BCAAs and the risk of MMD and clinical subtypes.

Methods

We conducted a case-control study of 360 adult MMD patients and 89 matched healthy controls consecutively recruited between September 2020 and December 2021. Serum level of BCAAs was quantified by liquid chromatography-mass spectrometry. The associations between BCAAs and risk of MMD were evaluated.

Results

Increased level of serum BCAAs was observed in MMD patients (P < 0.001). After adjusting for traditional confounders, the elevated BCAAs level was significantly associated with the risk of MMD (Q4 vs. Q1: odds ratio, 3.10 [95% CI, 1.29–7.50]). The risk of subtypes in MMD also increased with each increment in the quartiles of BCAAs. Furthermore, BCAAs offered substantial improvement in risk reclassification and discrimination for MMD and subtypes.

Conclusion

Higher level of circulating BCAAs was associated with increased risk of MMD and clinical subtypes. This study will help to elucidate the pathogenesis of MMD, which may provide the support for facilitating the treatments and preventions.
Is a high-risk clinical target volume required? Evaluation of the dosimetric feasibility based on T staging
Authors: Yuan Xingxing , Yan Chao , Peng Shiyi , Chen Zhiping , Lu Tianzhu , Gong Qiaoying , Qiu Yang , Xiong Wenming , Ao Fenghua , Li Guoqing , Li Jingao , Tu Ziwei
Published: September 2022

Background

Clinical target delineation is a primary focus in the field of radiotherapy. This study aimed to investigate whether high-risk clinical target volume can be removed in nasopharyngeal carcinoma patients with different T stages.

Materials and methods

We designed a test plan without the high-risk clinical target volume for 111 nasopharyngeal carcinoma patients and further compared the test plans with the treatment plans in the parameters of planning target volumes and the radiation dose to normal organs.

Results

Our data showed that when high-risk clinical target volume was abnegated, target coverage, conformity indices, and homogeneity indices of planning target volumes and doses of normal organs were not influenced in the T4 nasopharyngeal carcinoma patients, and more than 95% of the high-risk planning target volume area could still be covered by the 60 Gy dose line. However, only some T1–3 patients achieved the ideal dose coverage, and even fewer after induction chemotherapy (62.8% vs. 41.2%, p = 0.018). Gross tumor volume was positively correlated with the target coverage of the original high-risk planning target volume in the test-plan (p = 0.0001). Gross tumor volume can be used to predict whether the target coverage of high-risk planning target volume is more than 95% (area under the curve = 0.868).

Conclusion

Omitting high risk clinical target volume can be considered in patients with T4 nasopharyngeal carcinoma according to physical evaluations. However, this approach is only suitable for a specific subset of T1–3 patients.
Knockdown of NDUFC1 inhibits cell proliferation, migration, and invasion of hepatocellular carcinoma
Authors: Han Fang , Liu Junwei , Chu Hongwu , Cao Dan , Wu Jia , Fu Hong , Guo Anyang , Chen Weiqin , Xu Yingping , Cheng Xiangdong , Zhang Yuhua
Published: September 2022

Background

NADH: ubiquinone oxidoreductase subunit C1(NDUFC1) encodes a subunit of the Complex I, which may support the structural stability of Complex I and assist in its biogenesis. The expression and functional roles of NDUFC1 in hepatocellular carcinoma (HCC) remain unknown.

Result

We knocked down the expression of NDUFC1 in HCC cell lines to explore the effects of NDUFC1 downregulation on HCC in vitro. MTT assay determined that downregulation of NDUFC1 significantly inhibited cell proliferation. Flow cytometry with (propidium iodide) PI staining indicated silencing of NDUFC1 arrested cell cycle of BEL-7404 cells at G2 phase and SK-HEP-1 cells at S/G2 phase. Annexin V-PI double staining and flow cytometric analysis showed that the downregulation of NDUFC1 significantly increased the population of apoptotic cells. Wound-healing assay and transwell assay indicated that the downregulation of NDUFC1 suppressed the migration and invasion of HCC cells. According to the detection of complex1 activity, we found that the activity of NDUFC1 silenced group decreased, whereas the content of ROS increased. Furthermore, combined with bioinformatics analysis of senescence-related genes, we found that the silence of NDUFC1 in HCC could induce senescence and inhibit autophagy. In addition, NDUFC1 could correlate positively with cancer-related pathways, among which the p53 pathways and the PI3K/Akt/mTOR pathways. Finally, NDUFC1 is high expression in HCC specimens. High NDUFC1 expression was associated with poor prognosis and was an independent risk factor for reduced overall survival (OS).

Conclusions

Our study indicated, for the first time, that NDUFC1 is an independent risk factor for the poor prognosis of HCC patients. NDUFC1 may promote tumor progression by inhibiting mitochondrial Complex I and up-regulating ROS through multiple cancer-related and senescence-related pathways of HCC, including p53 pathways and PI3K/Akt/mTOR pathways. We suppose that NDUFC1 might be a potential target for the mitochondrial metabolism therapy of HCC.
Reversal of IKZF1-induced glucocorticoid resistance by dual targeting of AKT and ERK signaling pathways
Authors: Butler Miriam , Vervoort Britt M.T. , van Ingen Schenau Dorette S. , Jongeneel Lieneke , van der Zwet Jordy C.G. , Marke René , Meijerink Jules P.P. , Scheijen Blanca , van der Meer Laurens T. , van Leeuwen Frank N.
Published: September 2022

Although long-term survival in pediatric acute lymphoblastic leukemia (ALL) currently exceeds 90%, some subgroups, defined by specific genomic aberrations, respond poorly to treatment. We previously reported that leukemias harboring deletions or mutations affecting the B-cell transcription factor IKZF1 exhibit a tumor cell intrinsic resistance to glucocorticoids (GCs), one of the cornerstone drugs used in the treatment of ALL. Here, we identified increased activation of both AKT and ERK signaling pathways as drivers of GC resistance in IKZF1-deficient leukemic cells. Indeed, combined pharmacological inhibition of AKT and ERK signaling effectively reversed GC resistance in IKZF1-deficient leukemias. As inhibitors for both pathways are under clinical investigation, their combined use may enhance the efficacy of prednisolone-based therapy in this high-risk patient group.
Acupuncture for adult lung cancer of patient-reported outcomes: A systematic review and meta-analysis
Authors: Xi Ziqi , Wei Xuqiang , Ye Zi , Wang Ke , Zhou Jia
Published: September 2022

Purpose

This systematic review and meta-analysis aims to assess the effects of acupuncture on patient-reported outcomes (PROs) in adults with lung cancer.

Methods

Electronic databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (CQVIP), Wanfang Data, SinoMed, and gray literatures were retrieved from inception to 1 July 2022 for randomized controlled trials (RCTs). Acupuncture was defined as an experimental intervention, and the patients of the control groups included either treatment including conventional therapy (usual care, sham/placebo acupuncture, pharmacotherapy including Western medicine and Chinese traditional medicine). PROs for this study were measured by seven scales of primary outcomes including the Karnofsky Performance Status (KPS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Functional Assessment of Cancer Therapy-Lung, Functional Assessment of Cancer Therapy Lung Cancer Subscale, Leicester Cough Questionnaire (LCQ score), the Medical Outcomes Study (MOS) item short form health survey (SF-36), and the St George’s Respiratory Questionnaire, and 12 scales of secondary outcomes. Cochrane Collaboration’s tool was used to assess the risks of bias. Data were combined and analyzed with RevMan 5.4 and Stata/SE 16.0.

Results

We retrieved 3,002 lung cancer patients from 33 trials. KPS included with 1,000 patients showed that acupuncture could significantly improve the quality of life (QOL) compared with the control group regardless of different tumor–node–metastasis stages or the different stages of disease. The study showed that acupuncture significantly improved lung cancer–related symptoms in the QOL, pain, nausea and vomiting, insomnia, anxiety and depression, fatigue, and constipation compared with the control group. Eight RCTs reported the occurrence of adverse events, whereas four reported none and four RCTs reported that the events in the observation group were significantly less than those in the control group.

Conclusion

Acupuncture proved to be a promising intervention, both postoperatively and after chemotherapy, and should be recommended as a beneficial alternative strategy to promote PROs in lung cancer patients at all stages of application. Considering the low quality, we suggest more rigorous clinical trials of acupuncture for lung cancer in the future and more emphasis on the effect of acupuncture in patients with lung cancer on their PROs, mainly in the aspect of the QOL.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?, identifier [CRD42021274122].
Role of extracellular matrix architecture and signaling in melanoma therapeutic resistance
Authors: Popovic Ana , Tartare-Deckert Sophie
Published: September 2022

The extracellular matrix (ECM) is critical for maintaining tissue homeostasis therefore its production, assembly and mechanical stiffness are highly regulated in normal tissues. However, in solid tumors, increased stiffness resulting from abnormal ECM structural changes is associated with disease progression, an increased risk of metastasis and poor survival. As a dynamic and key component of the tumor microenvironment, the ECM is becoming increasingly recognized as an important feature of tumors, as it has been shown to promote several hallmarks of cancer via biochemical and biomechanical signaling. In this regard, melanoma cells are highly sensitive to ECM composition, stiffness and fiber alignment because they interact directly with the ECM in the tumor microenvironment via cell surface receptors, secreted factors or enzymes. Importantly, seeing as the ECM is predominantly deposited and remodeled by myofibroblastic stromal fibroblasts, it is a key avenue facilitating their paracrine interactions with melanoma cells. This review gives an overview of melanoma and further describes the critical roles that ECM properties such as ECM remodeling, ECM-related proteins and stiffness play in cutaneous melanoma progression, tumor cell plasticity and therapeutic resistance. Finally, given the emerging importance of ECM dynamics in melanoma, future perspectives on therapeutic strategies to normalize the ECM in tumors are discussed.
Proton-induced DNA damage promotes integration of foreign plasmid DNA into human genome
Authors: Katerji Meghri , Bertucci Antonella , Filippov Valery , Vazquez Marcelo , Chen Xin , Duerksen-Hughes Penelope J.
Published: September 2022

High-risk human papillomaviruses (HPVs) cause virtually all cervical cancer cases and are also associated with other types of anogenital and oropharyngeal cancers. Normally, HPV exists as a circular episomal DNA in the infected cell. However, in some instances, it integrates into the human genome in such a way as to enable increased expression of viral oncogenes, thereby leading to carcinogenesis. Since viral integration requires breaks in both viral and human genomes, DNA damage likely plays a key role in this critical process. One potentially significant source of DNA damage is exposure to elevated doses of ionizing radiation. Natural background radiation is ubiquitous; however, some populations, including radiological workers, radiotherapy patients, and astronauts, are exposed to significantly higher radiation doses, as well as to different types of radiation such as particle radiation. We hypothesize that ionizing radiation-induced DNA damage facilitates the integration of HPV into the human genome, increasing the risk of developing HPV-related cancers in the exposed population. To test this, we first determined the kinetics of DNA damage in keratinocytes exposed to ionizing radiation (protons) by assessing γ-H2AX foci formation using immunofluorescence (direct damage), and also measured ROS and 8-oxoG levels via DCFDA and Avidin-FITC (indirect damage).As anticipated, direct DNA damage was observed promptly, within 30 min, whereas indirect DNA damage was delayed due to the time required for ROS to accumulate and cause oxidative damage. Although radiation was lethal at high doses, we were able to establish an experimental system where radiation exposure (protons and X-rays) induced DNA damage dose-dependently without causing major cytotoxic effects as assessed by several cytotoxicity assays. Most importantly, we explored the impact of radiation exposure on integration frequency using a clonogenic assay and demonstrated that as predicted, proton-induced DNA damage promotes the integration of HPV-like foreign DNA in oral keratinocytes. Overall, the insights gained from this work enable us to better understand the contribution of radiation exposure and DNA damage to HPV-mediated carcinogenesis and direct us toward strategies aimed at preventing malignancies in HPV-infected individuals.
The expression and biological effect of NR2F6 in non-small cell lung cancer
Authors: Yang Shu lin , Guan Huan qin , Yang Hong bao , Chen Yao , Huang Xiao ying , Chen Lei , Shen Zhi fa , Wang Liang xing
Published: September 2022

Objective

This study aimed to explore the expression and effect of the nuclear receptor subfamily 2 group F member 6 (NR2F6) gene in non-small cell lung cancer (NSCLC) and provide an experimental basis for the targeted therapy of NSCLC.

Method

First, the expression of NR2F6 in lung cancer tissues was analyzed using the Gene Expression Omnibus and the Cancer Genome Atlas (TCGA) databases, and the expression of NR2F6 in lung cancer tissues and cells was verified by Western blotting and quantitative polymerase chain reaction. Next, the relationship between NR2F6 expression and the clinicopathological features of lung cancer was analyzed via immunohistochemistry, and the relationship between NR2F6 expression and prognosis was analyzed using the Kaplan–Meier Plotter. The influence of NR2F6 knockdown on the proliferation capacity of lung cancer cells was then verified at cell level. Finally, the expression of heterogeneous nuclear ribonucleoprotein D (HNRNPD) in lung cancer tissue was analyzed using the TCGA database and immunohistochemistry. The impact of HNRNPD knockdown on the proliferation capacity of lung cancer cells was verified at cell level, and the relationship between NR2F6 and HNRNPD was verified by co-immunoprecipitation.

Results

NR2F6 was highly expressed in lung cancer tissues and cells, and its expression was positively correlated with the depth of invasion, lymphatic metastasis, and clinical stage of lung cancer. High expression of NR2F6 in lung cancer was also significantly associated with poor prognosis. At cell level, NR2F6 knockdown was found to inhibit the proliferation of H460 and H358 in lung cancer cells. Furthermore, the TCGA database and immunohistochemical results showed that HNRNPD was highly expressed in lung cancer tissues and was highly consistent with NR2F6 expression in these tissues. Knockdown of HNRNPD also inhibited the proliferation of lung cancer cells. The co-immunoprecipitation experiment verified that NR2F6 interacted with HNRNPD.

Conclusion

NR2F6 may interact with HNRNPD to jointly regulate the progression of lung cancer, and this conclusion provides a new experimental basis for the study of the molecular targeted therapy of NSCLC.
A case report of the sustained and rapid response of bevacizumab in a TP53-positive breast cancer and liver metastatic patient through personalized medicine
Authors: Eskandarion Mohammad Reza , Tizmaghz Zahra , Andalib Bahram , Parsa Nasser , Emami Seyed Amir Hossein , Shahsiah Reza , Oghabian Mohammad Ali , Shirkoohi Reza
Published: September 2022

HER2-positive metastatic breast cancer is much less frequent than other subgroups of breast cancer. Treatment options for this cancer are mostly limited to systemic chemotherapy, which leads to moderate improvements. Targeted therapy against malignant breast cancer requires the identification of reliable biomarkers for personalized medicine to obtain the maximum benefit of this therapy. Any mutations in the TP53 signaling pathway can be considered as a significant causative factor of breast cancer, for which the identification of target genes plays an important role in selecting the appropriate treatment. The use of personalized gene expression profiling could be valuable to find the direct target of the treatment in this case. The present study assessed the genetic profile of an HER2-positive metastatic breast cancer patient (with a liver metastasis) and figured out a complete and sustained response to bevacizumab. According to the results of next-generation sequencing (NGS) analysis, the patient’s genetic profile showed an increased expression of p4EBP1 and PTEN and the activation of the mTOR signaling pathway with a mutation in the TP53 gene. Based on the common treatment of similar profiling, we administrated bevacizumab/Taxol/Gemzar chemotherapy up to six courses. Accordingly, as the response to treatment was revealed by reducing the volume of the liver metastasis from 4 to 1.4 cm, metastasectomy was performed as a complementary treatment. Hence, personalized gene expression profiling not only is useful for targeted therapy but also could be recommended to avoid prescription of non-responsive drugs.
Thyroid cancer harboring PTEN and TP53 mutations: A peculiar molecular and clinical case report
Authors: Colombo Carla , Pogliaghi Gabriele , Tosi Delfina , Muzza Marina , Bulfamante Gaetano , Persani Luca , Fugazzola Laura , Cirello Valentina
Published: September 2022

To date, the molecular mechanisms that underline aggressiveness and resistance to tyrosine kinase inhibitors in some thyroid carcinomas (TCs) are not known yet. We report the case of a young patient with a metastatic poorly differentiated (PDTC) and follicular thyroid carcinoma (FTC) refractory to conventional therapies and to Sorafenib. The patient, despite an initial partial response, died of progressive disease 21 months after diagnosis. The genetic analysis performed on the primary tumor and on lymph nodes and distant metastases allowed to identify a frameshift mutation (p.P248Tfs*5) in the PTEN gene, never described in TC. This mutation was present in the primary tumor and, with a lower allelic frequency, in metastases diagnosed after treatment with Sorafenib. Mutations in TP53 (p.C135Y and c.920-2A>G previously detected in anaplastic carcinomas and p.M133R never found in TC) were also detected in the primary tissue together with a mono-allelic expression of the p.C135Y mutant at RNA level. At metastatic sites level, we found only the TP53 splicing mutation c.920-2A>G. The presence of defects in mismatch repair (MMR) proteins and genomic instability was also evaluated. The primary tumor showed a partial expression of MMR proteins together with a strong genomic instability. In conclusion, we demonstrated that the rare combination of somatic PTEN and TP53 mutations in a patient with a metastatic FTC, together with the presence of tumor heterogeneity and genomic instability, might be associated with a high tumor aggressiveness and resistance to treatments.
Low-dose PD-1 inhibitor combined with lenvatinib for preemptive treatment of recurrence after liver transplantation for hepatocellular carcinoma: Case report and literature review
Authors: Jin Xin , Zhang Kangjun , Fang Taishi , Zeng Xinchen , Yan Xu , Tang Jianxin , Liang Ziming , Xie Linjie , Zhao Dong
Published: September 2022

Orthotopic liver transplantation (OLT), as one of the curative methods for the treatment of hepatocellular carcinoma (HCC), has brought hope to patients with HCC. However, treatment options for HCC recurrence and metastasis after liver transplantation are limited. Immune checkpoint inhibitor (ICI), such as programmed cell death protein 1 (PD-1) inhibitor, have been successfully used in advanced or metastatic HCC, but the data on the safety of PD-1 inhibitor after liver transplantation is limited. In this article, we report a 47-year-old patient with acute-on-chronic liver failure and multiple HCC who was successfully treated with liver transplantation. On the 45th day after OLT, the patient’s alpha fetoprotein (AFP) and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) were increased, and imaging examination showed no residual tumor. The patient had high risk factors for tumor recurrence before operation, so the possibility of tumor recurrence was considered. When the tumor markers showed an upward trend, we immediately treated the patient with lenvatinib 8 mg, after half a month, the AFP and AFP-L3 continued to increase compared with before. Then we used low-dose nivolumab 40mg, the patient’s AFP and AFP-L3 gradually decreased. One month later, a second low-dose nivolumab 40mg was given, and the patient’s tumor markers gradually decreased to normal. No acute rejection and other complications occurred during the treatment. So far, we have followed up this patient for 2 years, and no tumor recurrence was observed. To our knowledge, this is the first reported case using a low dose of nivolumab in combination with lenvatinib to prevent recurrence of HCC after liver transplantation.
Embryonic esophageal rhabdomyosarcoma in an adult male: A case report and literature review
Authors: Zhang Xiaoman , Li Guang
Published: September 2022

Basic principle

There exists a rare aggressive neoplasm called esophageal rhabdomyosarcoma. It originates in cells of the striated muscle or mesenchymal cells which differ from the striated muscle. This tumor has a high degree of malignancy and extensive metastasis. Masses of the sick people are at a high phase when going to hospital. Consequently, the prognosis is exceedingly bad.

Patient concerns

A 54-year-old male presented with dysphagia as the initial symptom. Gastroscopy showed an irregular protuberant lesion about 18–22 cm from the incisor. The lesion was observed to be pathological under gastroscopy and was diagnosed as an (esophageal) sarcoma.

Diagnosis

Embryonic esophageal rhabdomyosarcoma.

Interventions

After receiving two cycles of DP (docetaxel and cisplatin) chemotherapy in the local hospital, the patient received 60 Gy of radiotherapy in 30 fractions combined with chemotherapy at our hospital. Dysphagia was relieved, and the tumor appeared significantly shrunken on imaging after the treatment.

Outcomes

Lung metastasis occurred 1 month after radiotherapy, and the patient died of pulmonary edema on March 11, 2022.

Lessons

Previously reported cases of embryonic esophageal rhabdomyosarcoma are few. Theoretically, the disease should occur in adolescents; nevertheless, our case was a man who was in middle-aged; the neoplasm was in an unusual position: the upper part of the esophagus. Moreover, the patient initially had good response to the combination of radiotherapy and chemotherapy. Although he died 8 months after diagnosis, the presented data represent a valuable resource for understanding the survival benefits of treating embryonic esophageal rhabdomyosarcoma patients with radiotherapy combined with chemotherapy. In addition, we reviewed the previously reported literature, and a total of 17 cases of esophageal rhabdomyosarcoma were identified and analyzed.
Overcoming resistance to immune checkpoint inhibitors in hepatocellular carcinoma: Challenges and opportunities
Authors: Xie Qingqing , Zhang Pengfei , Wang Yuanyuan , Mei Wuxuan , Zeng Changchun
Published: September 2022

Hepatocellular carcinoma is one of the leading causes of cancer mortality globally, and its incidence is increasing. Immune checkpoint therapy has revolutionized the treatment of hepatocellular carcinoma over the past few years. However, only a limited proportion of patients with hepatocellular carcinoma respond to immunotherapy. Despite the significant breakthroughs, the molecular mechanisms that drive immune responses and evasion are largely unresolved. Predicting tumor response and resistance to immune checkpoint inhibitors is a significant challenge. In this review, we focus on the current research progress of immune checkpoint inhibitors in hepatocellular carcinoma. Importantly, this review highlights the underlying mechanisms of resistance to immune checkpoint inhibitors and summarizes potential strategies to overcome the resistance to immune checkpoint inhibitors in hepatocellular carcinoma.
Expression pattern of non-coding RNAs in non-functioning pituitary adenoma
Authors: Ghafouri-Fard Soudeh , Safarzadeh Arash , Akhavan-Bahabadi Mehdi , Hussen Bashdar Mahmud , Taheri Mohammad , Dilmaghani Nader Akbari
Published: September 2022

Non-functioning pituitary adenoma (NFPA) is a benign tumor arising from the adenohypophyseal cells. They can be associated with symptoms arising from mass effect. Although these tumors are regarded to be benign tumors, they are associated with increased comorbidity and mortality. Several studies have indicated abnormal expression of genes in these tumors. In the current study, we have used existing methods to identify differentially expressed genes (DEGs) including DE long non-coding RNAs (DElncRNAs) and DE microRNAs (DEmiRNAs) in NFPAs compared with normal samples. Then, we have assessed the relation between these genes and important signaling pathways. Our analyses led to identification of 3131 DEGs, including 189 downregulated DEGs (such as RPS4Y1 and DDX3Y) and 2898 upregulated DEGs (such as ASB3 and DRD4), and 44 DElncRNAs, including 8 downregulated DElncRNAs (such as NUTM2B-AS1 and MALAT1) and 36 upregulated DElncRNAs (such as BCAR4 and SRD5A3-AS1). GnRH signaling pathway, Tight junction, Gap junction, Melanogenesis, DNA replication, Nucleotide excision repair, Mismatch repair and N-Glycan biosynthesis have been among dysregulated pathways in NFPAs. Taken together, our study has revealed differential expression of several genes and signaling pathways in this type of tumors.
Berberine as a potential agent for breast cancer therapy
Authors: Zhong Xiao-Dan , Chen Li-Juan , Xu Xin-Yang , Liu Yan-Jun , Tao Fan , Zhu Ming-Hui , Li Chang-Yun , Zhao Dan , Yang Guan-Jun , Chen Jiong
Published: September 2022

Breast cancer (BC) is a common malignancy that mainly occurred in women and it has become the most diagnosed cancer annually since 2020. Berberine (BBR), an alkaloid extracted from the Berberidacea family, has been found with broad pharmacological bioactivities including anti-inflammatory, anti-diabetic, anti-hypertensive, anti-obesity, antidepressant, and anticancer effects. Mounting evidence shows that BBR is a safe and effective agent with good anticancer activity against BC. However, its detailed underlying mechanism in BC treatment remains unclear. Here, we will provide the evidence for BBR in BC therapy and summarize its potential mechanisms. This review briefly introduces the source, metabolism, and biological function of BBR and emphasizes the therapeutic effects of BBR against BC via directly interacting with effector proteins, transcriptional regulatory elements, miRNA, and several BBR-mediated signaling pathways. Moreover, the novel BBR-based therapeutic strategies against BC improve biocompatibility and water solubility, and the efficacies of BBR are also briefly discussed. Finally, the status of BBR in BC treatment and future research directions is also prospected.