Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

OBJECTIVE: To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), atrial natriuretic peptide (ANP), and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF), and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF. METHODS: Fifty SD rats were randomly divided into a normal group (n=10) and a modeling group (n=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a model group (n=9), a moxibustion group (n=8), a rapamycin (RAPA) group (n=9), and a moxibustion+RAPA group (n=9). In the moxibustion group, moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15), 15 min at each point in each intervention, once daily, for 4 consecutive weeks. In the RAPA group, RAPA solution was administered intraperitoneally at a dose of 1 mg/kg, once daily for 4 consecutive weeks. In the moxibustion+RAPA group, RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventricular fractional shortening (FS) were measured after modeling and intervention. After intervention, morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1, FSP1, ANP, and CollagenⅠ in myocardial tissue. RESULTS: Compared with the normal group, the EF and FS values decreased (P<0.01); necrosis, edema, degeneration, and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated, the structure of myocardial fibers was disarranged, the collagen fibers were obviously deposited and fibrosis increased (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue were elevated (P<0.01), while the protein and mRNA expression of FSP1 were reduced (P<0.01) in the model group. Compared with the model group, the moxibustion group showed that EF and FS increased (P<0.01); myocardial cell morphology was improved, and myocardial fibrosis was alleviated (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while the protein and mRNA expression of FSP1 increased (P<0.01, P<0.05). Compared with the model group, the myocardial fibrosis was increased (P<0.05); the total iron content and the protein and mRNA expression of TfR1, ANP, CollagenⅠ in myocardial tissue were increased (P<0.01), while protein and mRNA expression of FSP1 decreased (P<0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group, EF and FS were elevated (P<0.01, P<0.05); myocardial cells were improved in morphology, the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while protein and mRNA expression of FSP1 increased (P<0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group, the RAPA group showed the decrease in EF and FS (P<0.01), the worsened myocardial fibrosis (P<0.01), the increase in the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue (P<0.01), and the decrease in the protein and mRNA expression of FSP1 (P<0.01). CONCLUSION Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.
Animals ; Rats ; Heart Failure/physiopathology* ; Moxibustion ; Rats, Sprague-Dawley ; Male ; Receptors, Transferrin/genetics* ; Myocardium/metabolism* ; Acupuncture Points ; Humans ; Chronic Disease/therapy* ; Antigens, CD/metabolism*

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans ; Memory, Short-Term/physiology* ; Male ; Female ; Young Adult ; Transcranial Direct Current Stimulation/methods* ; Brain/physiology* ; Adult ; Electroencephalography ; Single-Blind Method

The incidence and mortality of colorectal cancer （CRC） in China have been on a steady rise. Current therapeutic approaches can curb the progression of CRC to a certain extent， but issues such as toxic side effects， high metastasis rate， and high recurrence rate cannot be ignored. In recent years， alkaloid components derived from traditional Chinese medicine （TCM） have demonstrated tremendous potential in the prevention and treatment of CRC due to their diverse structures， complex mechanisms， and broad biological activities. Representative alkaloids such as matrine， berberine and evodiamine exert anti-CRC effects through multiple pathways： regulating signaling pathways including Wnt/β-catenin， nuclear factor-κB， signal transducer and activator of transcription 3， and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin； inhibiting the proliferation， migration， and invasion of CRC cells； inducing cell apoptosis and autophagy； arresting the cell cycle progression； regulating the gut microbiota； suppressing cellular glycolysis； and inducing ferroptosis.

OBJECTIVE To explore the effects of Yueju Pill on depression and gastrointestinal function in depressed co-morbid functional dyspepsia mice.METHODS C57BL/6J mice were randomly divided into control group,model group,Yueju Pill low-dose group,Yueju Pill high-dose group and positive drug group.A co-morbidity model was constructed using chronic unpredictable mild stress(CUMS),and the mice were assessed for depression-like behaviour and neuronal damage by behavioural tests and Nissl staining;gastrointestinal function was assessed by HE staining of gastric and intestinal tissues,gastric emptying rate,and small intestinal propul-sive rate;PACAP,VIP,IL-6,TNF-α,and BDNF expression were detected by ELISA;PAC1-R,Vipr1,and Vipr2 protein expres-sion were detected by protein immunoblotting.RESULTS Mice in the model group showed depression-like behaviour,reduced num-ber of hippocampal nidus,slowed gastrointestinal motility,elevated serum inflammatory factors IL-6 and TNF-α(P＜0.05,P＜0.01),and reduced expression of PACAP,VIP,and BDNF(P＜0.05,P＜0.01),The PAC1-R,VPAC1-R,VPAC2-R expression de-creased in the hippocampus and gastric sinus,duodenal tissue(P＜0.05,P＜0.01).Compared with the model group,the low and high dose groups of Yueju Pill improved the above indexes except for Vipr1 and Vipr2(P＜0.05,P＜0.01).CONCLUSION Yueju Pill can reduce inflammatory factors through PACAP/PAC1-R,increase the level of BDNF,and improve the depression-like behaviour and gastrointestinal dysfunction in CUMS mice.

Objective To observe the effects of moxibustion on myocardial pathological morphology,α-smooth muscle actin(α-SMA)and chromosome 10 deletion phosphatase and tensin homologous protein(PTEN)/mammalian target of rapamycin(mTOR)signalling pathway in rats with chronic heart failure(CHF),and to explore the possible mechanism of moxibustion in attenuating myocardial fibrosis in rats with CHF.Methods According to the random number table method,60 male SD rats were divided into the normal group(n=10)and the surgery group(n=50),and the rats in the surgery group were ligated the left coronary artery to replicate the CHF model.According to the random number table method,40 successfully modelled rats were divided into the model group,the moxibustion group,the bpV(phen)group,and the moxibustion+bpV(phen)group,with 10 rats in each group.The normal and model groups were not given any intervention;in the moxibustion group,customized moxa sticks were used to moxibrate the bilateral"Feishu"(BL13)and"Xinshu"(BL15)on the back of the rats for 30 min at each point once a day;the bpV(phen)group was injected intraperitoneally with the bpV(phen)solution(0.15 mg/kg)twice a week;the moxibustion+bpV(phen)group was based on the bpV(phen)group,and moxibustion was applied according to the moxibustion group.The intervention was carried out for 4 weeks.The general conditions of rats,such as feeding and activity were observed;HE staining was used to detect morphological changes of the cardiomyocytes;Masson staining was used to detect myocardial fibrosis;the cardiac echocardiography was used to detect ejection fraction(EF)and fractional shortening(FS);real-time PCR was used to detect the mRNA expressions of PTEN and mTOR in the cardiac muscle tissues;protein expressions of PTEN,mTOR,α-SMA in rat myocardial tissue were detected by Western blotting.Results Compared with the normal group,rats in the model group had altered cardiomyocyte morphology,severe damage to myocardial fiber structure,significantly lower EF,FS,and mTOR mRNA and protein expressions,and significantly higher PTEN,α-SMA protein expressions and PTEN mRNA expression(P<0.05).Compared with the model group,myocardial ultrastructural damage was attenuated in the moxibustion group,bpV(phen)group,and moxibustion+ bpV(phen)group,and EF,FS,and mRNA and protein expressions of mTOR were significantly higher,α-SMA protein expression was significantly lower,and mRNA and protein expressions of PTEN were significantly lower(P<0.05).Compared with the moxibustion+bpV(phen)group,myocardial ultrastructural damage was worsen in the moxibustion and bpV(phen)groups,with significantly lower EF,FS,and mRNA and protein expressions of mTOR,significantly higher α-SMA protein expression,and significantly higher mRNA and protein expressions of PTEN(P<0.05).Conclusion Moxibustion can improve the pathological morphology and function of cardiomyocytes and attenuate myocardial fibrosis in rats with CHF,and its mechanism may be related to the down-regulation of PTEN expression,and then the up-regulation of mTOR expression.

Objective:To demonstrate any role of iron metabolism in the inhibition by aerobic exercise of myocardial apoptosis in atherosclerotic mice.Methods:Eight-week-old male ApoE -/- gene knockout mice were randomly divided into a control group, a model group and an aerobic exercise group, each of 9. A model of atherosclerosis was induced in the rats of the model and aerobic exercise groups by feeding them a " western" diet for 12 weeks. During that time the aerobic exercise group only was given aerobic exercise training. The control group was fed normal rat chow during that period. Myocardial apoptosis was detected using TUNEL staining, and the expression and localization of ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) in the myocardium used immunohistochemistry. Western blotting was applied to detect the FTH1 and GPX4 protein levels, and iron deposition in the myocardium was detected using Prussian blue staining. Iron, lipid peroxide malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) in the myocardial tissue were also measured. Results:The TUNEL staining showed significant apoptosis in the model group. In the aerobic exercise group it was significantly less. There was obvious iron deposition in the myocardia of the model group, which was significantly reduced in the aerobic exercise group. The average FTH1 and GPX4 levels in the model group were lower than in the control group, and significantly elevated in the aerobic exercise group.in the aerobic exercise group than in the model group. Iron and MDA levels in the aerobic exercise group were significantly lower, on average, than among the model group, while that of GSH-PX was significantly higher.Conclusions:Aerobic exercise can significantly inhibit cardiomyocyte apoptosis in atherosclerotic mice. The mechanism may be closely related to better iron metabolism, reduced oxidative stress and the inhibition of iron overload.

ObjectiveTo explore the effects of Naozhenning granules on the memory function and neuron cells in the rat model of post-concussion syndrome based on mitochondrial biosynthesis. MethodSPF-grade Wistar rats were used to establish the multiple cerebral concussion （MCC） model by the weight-drop method. The successfully modeled rats were assigned into model， piracetam （0.324 g·kg^-1）， and low-， medium-， and high-dose （2.25， 4.5， and 9 g·kg^-1， respectively） Naozhenning groups. The rats were administrated with corresponding drugs by gavage and those in the blank group and model group were administrated the same volume of normal saline once a day for 14 days. The general state of rats was observed before and after treatment. The open field test and new object recognition test were conducted to examine the motor and memory abilities of rats. Hematoxylin-eosin staining was employed to observe the pathological changes of cortical neurons in rats. Western blot and real-time polymerase chain reaction were employed to determine the protein and mRNA levels， respectively， of peroxisome proliferator-activated receptor γ-coactivator-1α （PGC-1α）， nuclear respiratory factor-1 （NRF-1）， and transcription factor A mitochondrial （TFAM） in rat cortex. ResultCompared with the blank group， the model group showed anxious and manic mental status， yellow and messy fur， and reduced food intake. In the open field experiment， the model group showed reduced total movement distance， times of entering the central grid， and times of rearing decreased and increased resting time compared with the blank group （P<0.01）. The model group had lower recognition index of new objects than the blank group （P<0.01）. In addition， the modeling caused reduced neurons with sparse distribution and deformed， broken， and irregular nucleoli and down-regulated the mRNA and protein levels of PGC-1α， NRF-1， and TFAM in the cortex （P<0.01）. Compared with the model group， piracetam and Naozhenning improved the mental state， coat color， food intake， and activities of rats. In the open field test， piracetam and Naozhenning increased the total movement distance， the times of entering the central grid， and the times of rearing and shortened the resting time （P<0.05， P<0.01）. The piracetam and Naozhenning groups had higher recognition index of new objects than the model group （P<0.05， P<0.01）. Compared with the model group， the piracetam and Naozhenning groups showed increased neurons with tight arrangement and large and round nuclei， and some cells with irregular morphology and turbid cytoplasm. Furthermore， piracetam and medium-dose Naozhenning upregulated the protein levels of PGC-1α， NRF-1， and TFAM （P<0.01）. Low-dose Naozhenning upregulated the protein levels of NRF-1 and TFAM （P<0.01）， and high-dose Naozhenning upregulated the protein levels of PGC-1α and TFAM in the cortex （P<0.01）. The mRNA levels of PGC-1α， NRF-1， and TFAM in the cortex were upregulated in the piracetam group and Naozhenning groups （P<0.05， P<0.01）. ConclusionNaozhenning granules can improve the motor， memory， and learning， repair the neuronal damage， and protect the nerve function in the rat model of MCC by promoting mitochondrial biosynthesis.