Changed brain entropy and functional connectivity patterns induced by electroconvulsive therapy in majoy depression disorder.

OBJECTIVE: Our objective is to innovatively integrate both linear and nonlinear characteristics of brain signals in Electroconvulsive Therapy (ECT) research, with the goal of uncovering deeper insights into the pathogenesis of Major Depressive Disorder (MDD) and identifying novel targets for other physical intervention therapies. METHODS: We measured brain entropy (BEN) in 42 MDD patients and 42 matched healthy controls (HC) using rs-fMRI data. Brain regions that differed significantly in patients with MDD before and after ECT were extracted. Then, we use these brain regions as seed points to investigate the differences in whole-brain resting-state functional connectivity (RSFC) patterns before and after ECT. RESULTS: Compared to HCs, patients had higher BEN levels in the right precuneus (PCUN.R) and right angular gyrus (ANG.R). After ECT, patients had lower BEN levels in the PCUN.R and ANG.R. Compared with before ECT, patients showed significantly increased RSFC after ECT between the PCUN.R and right middle temporal gyrus and ANG.R. Significantly increased RSFC was observed between the ANG.R and right middle frontal gyrus and right supramarginal gyrus after ECT. CONCLUSION: Combining the linear and nonlinear characteristics of brain signals can effectively explore the pathogenesis of depression and provide new targets for ECT.

Electroconvulsive therapy enhances degree centrality in the orbitofrontal cortex in depressive rumination.

Depressive rumination has been implicated in the onset, duration, and treatment response of refractory depression. Electroconvulsive therapy (ECT) is remarkably effective in treatment of refractory depression by modulating the functional coordination between brain hubs. However, the mechanisms by which ECT regulates depressive rumination remain unsolved. We investigated degree centrality (DC) in 32 pre- and post-ECT depression patients as well as 38 matched healthy controls. An identified brain region was defined as the seed to calculate functional connectivity (FC) in whole brains. Rumination was measured by the Ruminative Response Scale (RRS) and its relationships with identified DC and FC alterations were examined. We found a significant negative correlation between DC of the right orbitofrontal cortex (rOFC) before ECT and brooding level before and after treatment. Moreover, rOFC DC increased after ECT. DC of the left superior temporal gyrus (lSTG) was positively correlated with reflective level before intervention, while lSTG DC decreased after ECT. Patients showed elevated FC in the rOFC with default mode network. No significant association was found between decreased RRS scores and changes in DC and FC. Our findings suggest that functional changes in rOFC and lSTG may be associated with the beneficial effects of ECT on depressive rumination.

Dynamic and static changes of amplitude of low-frequency fluctuations in anti­N­methyl­D­aspartate receptor encephalitis.

BACKGROUND: Previous neuroimaging research has examined static local brain activity changes in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. However, the dynamic properties of local brain activity in anti-NMDAR encephalitis remain unknown. METHODS: This study used a combination of the amplitude of low-frequency fluctuation (ALFF) method and a sliding-window dynamic analysis approach to examine the time-varying local brain activity changes in anti-NMDAR encephalitis. RESULTS: Results showed that patients with anti-NMDAR encephalitis exhibited increased dynamic ALFF (dALFF) variability in the left inferior occipital gyrus compared to healthy controls (HCs), while the patients exhibited decreased sALFF in widespread regions, including the left inferior frontal gyrus, left medial frontal gyrus, bilateral putamen, left medial superior frontal gyrus. dALFF had superior classification performance in distinguishing anti-NMDAR encephalitis patients from HCs over sALFF, but sALFF was correlated with multiple clinical and neuropsychological measures. CONCLUSIONS: These findings may shed light on anti-NMDAR encephalitis brain dysfunction from the perspective of dynamic local brain activity. sALFF and dALFF analyses provide complementary information, emphasizing the potential usefulness of combining sALFF and dALFF in elucidating the neuropathological mechanisms of autoimmune encephalitis and may ultimately inform future disease diagnosis.

Altered brain entropy and functional connectivity patterns in generalized anxiety disorder patients.

BACKGROUND: Generalized anxiety disorder (GAD) is a highly prevalent disease characterized by chronic, pervasive, and intrusive worry. Previous resting-state functional MRI (fMRI) studies on GAD have mainly focused on conventional static linear features. Entropy analysis of resting-state functional magnetic resonance imaging (rs-fMRI) has recently been adopted to characterize brain temporal dynamics in some neuropsychological or psychiatric diseases. However, the nonlinear dynamic complexity of brain signals has been rarely explored in GAD. METHODS: We measured the approximate entropy (ApEn) and sample entropy (SampEn) of the resting-state fMRI data from 38 GAD patients and 37 matched healthy controls (HCs). The brain regions with significantly different ApEn and SampEn values between the two groups were extracted. Using these brain regions as seed points, we also investigated whether there are differences in whole brain resting-state function connectivity (RSFC) pattern between GADs and HCs. Correlation analysis was subsequently conducted to investigate the association between brain entropy, RSFC and the severity of anxiety symptoms. A linear support vector machine (SVM) was used to assess the discriminative power of BEN and RSFC features among GAD patients and HCs. RESULTS: Compared to the HCs, patients with GAD showed increased levels of ApEn in the right angular cortex (AG) and increased levels of SampEn in the right middle occipital gyrus (MOG) as well as the right inferior occipital gyrus (IOG). Contrarily, compared to the HCs, patients with GAD showed decreased RSFC between the right AG and the right inferior parietal gyrus (IPG). The SVM-based classification model achieved 85.33 % accuracy (sensitivity: 89.19 %; specificity: 81.58 %; and area under the receiver operating characteristic curve: 0.9018). The ApEn of the right AG and the SVM-based decision value was positively correlated with the Hamilton Anxiety Scale (HAMA). LIMITATIONS: This study used cross-sectional data and sample size was small. CONCLUSION: Patients with GAD showed increased level of nonlinear dynamical complexity of ApEn in the right AG and decreased linear features of RSFC in the right IPG. Combining the linear and nonlinear features of brain signals may be used to effectively diagnose psychiatric disorders.

Study on the Evaluation of Lung Cancer Patients from the Three Aspects of Emotion.

In recent years, epidemiological survey data have shown that lung cancer is the tumor with the fastest increase in cancer incidence and mortality in China. The incidence and mortality of lung cancer in China rank first among tumors, and 80% of patients die within one year of diagnosis. This paper aims to study the evaluation of lung cancer patients from three aspects of emotion, coping style, and Quality of Life (QoL), expounding on the changes in emotion, coping style, and QoL in lung cancer patients after chemotherapy. We assess the negative emotions and survival of lung cancer patients after chemotherapy quality satisfaction survey research. We investigate the general data, QoL, and coping styles of 219 lung cancer patients undergoing chemotherapy before, during, and after chemotherapy based on the artificial intelligence processor. All survey data are input into SPSS 19 for descriptive and relevant statistical analysis. The experimental results show that under a survey of 219 lung cancer chemotherapy patients with negative emotions and QoL satisfaction after chemotherapy, at a significance level of = 0.05, there is a linear regression relationship between mental resilience and anxiety and depression.

Prognostic Nutritional Index and Neutrophil/Lymphocyte Ratio Can Serve as Independent Predictors of the Prognosis of Hepatocellular Carcinoma Patients Receiving Targeted Therapy.

Objective: The prognostic nutritional index (PNI) is an immunonutritional indicator, and the neutrophil/lymphocyte ratio (NLR) reflects the inflammatory status. This research intends to determine the implications of NLR and PNI in evaluating the outcome of hepatocellular carcinoma (HCC) patients undergoing targeted therapy (TT). Methods: We retrospectively analyzed 83 patients' records with sorafenib treatment for advanced HCC in the Second Affiliated Hospital of Anhui Medical University. Patient records comprised general data and blood routines. The PNI and NLR values were calculated using the serum albumin levels (ALB), neutrophil (NEU) count, and lymphocyte (LY) count. The optimal thresholds of the PNI and NLR for predicting HCC patients' outcomes were calculated by X-tile. Patients were further assigned to low- and high-groups of PNI and NLR according to their thresholds. By using the Cox proportional hazards regression models, univariate and multivariate analyses were conducted to identify risk factors influencing the patient's prognosis. Results: The participants were assigned to the corresponding low-PNI (≤42.9; n = 10) and high-PNI (>42.9; n = 73) groups, as well as low-NLR (≤2.4; n = 64) and high-NLR (>2.4; n = 19) groups based on the critical values of PNI (42.9) and NLR (2.4) obtained through the X-tile calculation. A higher overall survival (OS) rate was observed in the high-PNI group and low-NLR group, than in the low-PNI group and high-NLR group, respectively. The disease control rate showed no evident difference between the groups. The PNI and NLR were of high reliability in predicting the OS of patients. Cox multivariate analysis identified the independence of the PNI and NLR as prognostic factors for patients receiving TT for advanced HCC. Conclusions: The pretreatment PNI and NLR levels have great prognostic implications for advanced HCC patients receiving TT. A higher PNI and a lower NLR suggest a higher postoperative survival rate.

Astragaloside IV suppresses migration and invasion of TGF-ß1-induced human hepatoma HuH-7 cells by regulating Nrf2/HO-1 and TGF-ß1/Smad3 pathways.

Astragaloside IV (AS-IV), one of the major compounds extract from Astragalus membranaceus, has shown attractive anti-cancer effects in certain malignancies. Oxidative stress (OS) is considered as a crucial factor in promoting the progression of hepatocellular carcinoma (HCC). In response to OS, nuclear factor erythroid 2-related factor 2 (Nrf2) upregulates and induces heme oxygenase 1 (HO-1) to combat oxidative damages. The phosphorylation of the COOH-terminal of Smad3 (pSmad3C) activates p21 to resist HCC progression, while the phosphorylation of the linker region of Smad3 (pSmad3L) up-regulates c-Myc transcription to exert promoting effect towards HCC. This study aimed to explore whether AS-IV suppresses migration and invasion of human hepatoma HuH-7 cells by regulating Nrf2/HO-1 and TGF-ß1/Smad3 pathways. HuH-7 cells were induced with TGF-ß1 (9 or 40 pM) to establish HCC model in vitro and pretreated with AS-IV at different concentration (5, 10, and 20 µM) for 24 h. Cell proliferation, migration, invasion, and intracellular reactive oxygen species (ROS) of HuH-7 cells were measured. The expression of Nrf2, pSmad3C, Nrf2/pNrf2, HO-1, pSmad3C/3L, c-Myc, and p21 were detected. Exposure of HuH-7 cells to TGF-ß1 enhanced the cell proliferation, migration, invasion, and ROS production. Pretreatment with AS-IV (5, 10, and 20 µM) significantly reduced the cell proliferation, migration, invasion, and ROS production in HuH-7 cells. Furthermore, AS-IV increased the expressions of Nrf2/pNrf2, HO-1, pSmad3C, and p21, meanwhile reduced the expressions of pSmad3L and c-Myc. In conclusion, our study suggested that AS-IV inhibit HuH-7 cells migration and invasion, which related to activate Nrf2/HO-1 pathway, up-regulation pSmad3C/p21 pathway, and down-regulation pSmad3L/c-Myc pathway. The present research supports the notion that AS-IV may be a latent agent for the treatment of HCC.

Targeting the JAK/STAT Signaling Pathway for Breast Cancer.

Breast cancer is the most common malignant tumor in women worldwide. Traditional ways of treatment, including radiotherapy and endocrine therapy, for breast cancer have inevitable side effects. In recent decades, targeted therapies for breast cancer have rapidly advanced and shown a promising future. The JAK/STAT signaling pathway has been shown to play important roles in tumorigenesis, maintenance and metastasis of breast cancer. Hence, many small molecule inhibitors of JAK and STAT proteins have been developed. These inhibitors exhibit potent inhibitory effects on breast cancer in both cellular and animal models, and even some of them have already been in clinical trials. This review article discussed the JAK/STAT signal transduction pathway in the pathogenesis of breast cancer, and the potential for the application of JAK/STAT inhibitors in breast cancer treatment.

Expression and characterization of recombinant human lactoferrin in edible alga Chlamydomonas reinhardtii.

Lactoferrin (LF) is a naturally occurring iron-binding glycoprotein with a variety of biological functions. It has increasing demand every year and huge market potential. In this study, we explored the feasibility of expressing human LF (hLF) in edible algae C. reinhardtii. A codon-optimized hLF gene was synthesized, inserted into pCAMBIA-1301C and transformed into C. reinhardtii SP strain. In total, 7 hLF-expressing clones were selected with clone 121 exhibiting the highest expression level. The hLF-containing algal extract significantly inhibited the growth of bacteria such as Escherichia coli and Klebsiella variicola. During acute toxicity experiment no acute toxicity was detected, especially on changes of the body weight and histopathology of organs. The recombinant hLF possessed a similar or modestly reduced stability compared to commercial hLF standard. Our data indicated that expression of hLF in C. reinhardtii is feasible and paved a way to commercial production of lactoferrin using edible Chlamydomonas expression system. Abbreviations: atrazine chlorohydrolase gene (atzA); bovine serum albumin (BSA); human LF (hLF); lactoferrin (LF); Luria-Bertani (LB); quantitative reverse transcriptase PCR (qRT-PCR) ; SDS polyacrylamide gel electrophoresis (SDS-PAGE); Tris-acetate phosphate (TAP); western blotting (WB).

Directed Evolution of Dunaliella salina Ds-26-16 and Salt-Tolerant Response in Escherichia coli.

Identification and evolution of salt tolerant genes are crucial steps in developing salt tolerant crops or microorganisms using biotechnology. Ds-26-16, a salt tolerant gene that was isolated from Dunaliella salina, encodes a transcription factor that can confer salt tolerance to a number of organisms including Escherichia coli (E. coli), Haematococcus pluvialis and tobacco. To further improve its salt tolerance, a random mutagenesis library was constructed using deoxyinosine triphosphate-mediated error-prone PCR technology, and then screened using an E. coli expression system that is based on its broad-spectrum salt tolerance. Seven variants with enhanced salt tolerance were obtained. Variant EP-5 that contained mutation S32P showed the most improvement with the E. coli transformant enduring salt concentrations up to 1.54 M, in comparison with 1.03 M for the wild type gene. Besides, Ds-26-16 and EP-5 also conferred E. coli transformant tolerance to freezing, cold, heat, Cu2+ and alkaline. Homology modeling revealed that mutation S32P in EP-5 caused the conformational change of N- and C-terminal α-helixes. Expression of Ds-26-16 and EP-5 maintained normal cellular morphology, increased the intracellular antioxidant enzymatic activity, reduced malondialdehyde content, and stimulated Nitric Oxide synthesis, thus enhancing salt tolerance to E. coli transformants.

Research progress in physicochemical characteristics of lactoferrin and its recombinant expression systems.

Lactoferrin is an iron-binding glycoprotein with a molecular weight of about 80 kDa that belongs to the transferrin family. Due to its unique physical and chemical properties, lactoferrin has a variety of biological functions including antibacterial, antiviral, anticancer, immunomodulatory activities and regulation of iron absorption. High-yield production of recombinant lactoferrin with biological activity and its application in clinical treatment have been a hot topic for long time. With the development of genetic engineering techniques, various expression systems have been developed to produce recombinant lactoferrin. In this review, we summarize physicochemical characteristics, biological activities, clinical studies and current recombinant expression systems of lactoferrin, in order to provide references for its clinical application.