The response of Golgi protein 73 to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma may relate to the influence of certain chemotherapeutics

BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoemboliza- tion （TACE） have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients af- ter TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS： Blood samples were collected from 72 HCC pa- tients, before TACE, at day I and day 30 after TACE. GP73 lev- els were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents （5-FU and pirarubicin） on GP73 expression were tested in three HCC cell lines （HepG2, HCCLM3 and MHCC97H）. RESULTS： The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure （P〈0.05）. There was no statistical differ- ence between the two time points after TACE, nor correlationbetween GP73 levels and dinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, signifi- cantly increased GP73 expression in three cell lines. CONCLUSIONS： Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

Risk factors and therapeutic results of early local recurrence after transcatheter arterial chemoembolization

AIM: To identify factors affecting early local recurrence after transcatheter arterial chemoembolization (TACE) and investigate treatments and outcomes for local recurrence.

Advanced imaging techniques in the therapeutic response of transarterial chemoembolization for hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the major causes of morbidity and mortality in patients with chronic liver disease. Transarterial chemoembolization(TACE) can significantly improve the survival rate of patients with HCC and is the first treatment choice for patients who are not suitable for surgical resections. The evaluation of the response to TACE treatment affects not only the assessment of the therapy efficacy but also the development of the next step in the treatment plan. The use of imaging to examine changes in tumor volume to assess the response of solid tumors to treatment has been controversial. In recent years, the emergence of new imaging technology has made it possible to observe the response of tumors to treatment prior to any morphological changes. In this article, the advances in studies reporting the use of computed tomography perfusion imaging, diffusionweighted magnetic resonance imaging(MRI), intravoxel incoherent motion, diffusion kurtosis imaging, magnetic resonance spectroscopy, magnetic resonance perfusionweighted imaging, blood oxygen level-dependent MRI, positron emission tomography(PET)/computed tomography and PET/MRI to assess the TACE treatment response are reviewed.

Computed tomography perfusion in evaluating the therapeutic effect of transarterial chemoembolization for hepatocellular carcinoma

AIM： To prospectively assess the changes in parameters of computed tomography （CT） perfusion pre- and post-transarterial chemoembolization （TACE） of hepatocellular carcinoma （HCC） in different treatment response groups, and to correlate the changes with various responses of HCC to TACE. METHODS： Thirty-nine HCC patients underwent CT perfusion examinations pre-（1 d before TACE） and post-treatment （4 wk after TACE）. The response evaluation criteria for solid tumors （RECIST） were referred to when treatment responses were distributed. Wilcoxon-signed ranks test was used to compare the differences in CT perfusion parameters pre- and post- TACE for different response groups. RESULTS： Only one case had treatment response to CR and the CT perfusion maps of post-treatment lesion displayed complete absence of signals. In the PR treatment response group, hepatic artery perfusion （HAP）, hepatic arterial fracture （HAF） and hepatic blood volume （HBV） of viable tumors post-TACE were reduced compared with pre-TACE （P = 0.001, 0.030 and 0.001, respectively）. In the SD group, all CT perfusion parameters were not significantly different pre- and post-TACE. In the PD group, HAP, HAl=, portal vein perfusion （PVP） and hepatic blood flow （HBF） of viable tumors post-TACE were significantly increased compared with pre-TACE （P = 0.005, 0.012, 0.035 and 0.005, respectively）. CONCLUSION： Changes in CT perfusion parameters of viable tumors are correlated with different responses of HCC to TACE. Therefore, CT perfusion imaging is a feasible technique for monitoring response of HCC to TACE.

Therapeutic effect of transcatheter arterial chemoembolization and percutaneous injection of acetic acids on primary liver cancer

BACKGROUND: The resection rate of primary liver tumor in China is only about 20%. A lot of patients with moderate and advanced liver tumor may lose the chance of opera- tion. The objective of present research was to study the ef- ficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous injection of chemical agents and acetic acids in the treatment of patients with primary liver cancer (PLC). METHODS: Thirty-three patients with middle and ad- vanced stage of PLC were divided into two groups: percu- taneous injection of chemical agents and acetic acids (15 patients, group A) and TACE (18 patients, group B). RESULTS: Tumor diameter and serum AFP level reduced to 86.6% and 83.3% in group A, and 55.5% and 40% in group B, respectively. There was significant difference be- tween the two groups ( P < 0 . 0 1 ) . The 1-, 2-, 3-, 4-year survival rates of group A were 96.7%, 86.6%, 51.3%, 33.3%, respectively and in group B were 66.7%, 44.4%, 16.7%, 0%, respectively (P<0.01). CONCLUSION: TACE combined with percutaneous injec- tion of chemical agents and acetic acids is efficacious to in- crease the survival rate of patients with PLC.

Intravoxel Incoherent Motion Diffusion Weighted Imaging for the Therapeutic Response of Transarterial Chemoembolization for Hepatocellular Carcinoma

Background: Intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) can not only observe the diffusion of tissue water molecules but also reflect the blood perfusion information of tissue microcirculation. IVIM-DWI has been applied in many clinical areas. However, few studies have addressed the use of IVIM-DWI for the evaluation of transarterial chemoembolization (TACE) response in hepatocellular carcinoma (HCC) patients. Objectives: The purpose of the present study was to explore the role of IVIM-DWI for the therapeutic response of TACE for HCC. Materials and Methods: Twenty patients underwent IVIM-DWI scan on a 3.0T magnetic resonance imaging instrument 1 - 3 days before and 30 to 40 days after TACE. The values of IVIM-DWI parameters, including standard apparent diffusion coefficient (ADC), pure diffusion coefficient (Dslow), pseudo-diffusion coefficient (Dfast) and perfusion fraction (f) were measured. The values of IVIM-DWI parameters before and after TACE were compared using paired t tests. The values between responsive and non-responsive groups were compared using independent-samples t test. P 0.05 indicated statistical significance. Results: After TACE, the ADC and Dslow values in the tumors increased significantly, and the values of Dfast decreased significantly, while the values of f value did not change obviously. The ADC values in responsive group were remarkably higher than those in non-responsive group, the Dfast values in responsive group were significantly lower than those in non-responsive group, but the values of Dslow and f between the two groups were not different significantly. Conclusions: IVIM-DWI parameters can be used as potential markers for the therapeutic response of TACE for HCC.

Therapeutic Effects of All Trans-retinoitc Acid Combined with Transarterial Chemoembolization on Walker-256 Hepatoma in Rats

In order to investigate the inhibitory effects of all trans-retinoitc acid(ATRA)on differentiation and apoptosis of Walker-256 hepatocellular carcinoma cells and the therapeutic effects of ATRA combined with transarterial chemoembolization(TACE)on rat Walker-256 transplanted hepatocarcinoma,Walker-256 hepatocarcinoma cell lines were treated with ATRA at different concentrations.After culture for 48h,the inhibitory rate of cell proliferation was determined by MTT assay;the changes of Fas and Bcl-2mRNA expres...

Analysis on the Clinical Therapeutic Effect of Hepatic Artery Chemoembolization in the Treatment of Advanced Liver Cancer

Objective:To analyze the clinical efficacy of hepatic artery chemoembolization in the treatment of advanced liver cancer.Methods:124 patients with advanced liver cancer admitted to our hospital from September 2019 to November 2020 were selected as the research subjects of this paper.The patients with advanced liver cancer were divided into experimental group and control group.The control group was treated with radiofrequency ablation alone,and the experimental group was administered hepatic arterial chemoembolization.The improvement in physical indicators and the incidence of adverse reactions between the two groups were compared.Results:The alpha-fetoprotein(AFP)index and serum total bilirubin(TBIL)index of the experimental group were lower than those of the control group,and the alanine aminotransferase(ALT)index was higher than that of the control group.There were differences in the comparison of liver function indices between the two groups which were statistically significant.After treatment,there were 3 cases of fever,4 cases of vomiting,8 cases of bone marrow transplantation,4 cases of abdominal pain,2 cases of proteinuria,and 1 case of diarrhea occurred in the experimental group;whereas there were 6 cases of fever,8 cases of vomiting,14 cases of bone marrow transplantation,7 cases of abdominal pain,5 cases of proteinuria,and 6 cases of diarrhea occurred in the control group.The difference in incidence of adverse reactions between patients after different treatment interventions was statistically significant.Analyzing the remission rate of tumor diseases in patients,the remission rate of the experimental group was higher than that of the control group,and the difference in the remission rate between the two groups of patients was statistically significant.Conclusion:The implementation of hepatic arterial chemoembolization for patients with advanced liver cancer can promote the improvement of the patient's short-term treatment efficacy,enhance the liver functions of the patient,reduce the incidence of adverse reactions,improve the efficiency of the patient's body rehabilitation,and enhance the quality of life of the patient after treatment.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Combined transarterial chemoembolization and tislelizumab for patients with unresectable hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)often presents as unresectable,necessitating effective treatment modalities.Combining transarterial chemoembolization(TACE)with immunotherapy and targeted therapy has shown promise,yet real-world evidence is needed.AIM To investigate effectiveness and safety of TACE with tislelizumab±targeted therapy for unresectable HCC in real-world setting.METHODS This retrospective study included patients with unresectable HCC receiving combined treatment of TACE and tislelizumab.The clinical outcomes included progression-free survival(PFS),overall survival(OS),objective response rate(ORR),and disease control rate(DCR).All patients were evaluated according to the mRECIST criteria.The adverse event(AE)was also assessed.RESULTS In this study of 56 patients with median follow-up of 10.9 months,7 had previous immunotherapy.Tislelizumab was administered before TACE in 21(37.50%)and after in 35(62.50%)patients,with 91.07%receiving concurrent targeted therapy.Median PFS was 14.0(95%CI:7.0-18.00)months,and OS was 28(95%CI:2.94-53.05)months.Patients with prior immunotherapy had shorter PFS(6 vs.18 months,P=0.006).Overall ORR and DCR were 82.14%and 87.50%.Grade≥3 treatment-related AEs included increased alanine aminotransferase(8.93%),aspartate aminotransferase(10.71%),and total bilirubin(3.57%).CONCLUSION The combination of TACE and tislelizumab,with or without targeted therapy,demonstrated promising efficacy and safety in unresectable HCC,especially in immunotherapy-naive patients,warranting further prospective validation studies.

Meta-analysis of transarterial chemoembolization combined with cryoablation vs transarterial chemoembolization alone for≥5 cm hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks sixth globally in cancer incidence and third in mortality rates.Unfortunately,over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations,poor physical condition,and limited organ availability upon diagnosis.Clinical guidelines endorse transarterial chemoembolization(TACE)as the frontline treatment for intermediate to advanced-stage HCC.Cryoablation(CRA)is an emerging local ablative therapy increasingly used in HCC management.Recent studies suggest that combining CRA with TACE offers complementary and synergistic effects,potentially improving long-term survival rates.However,the superiority of combined TACE+CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further investigation.AIM To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of≥5 cm.METHODS PubMed,EMBASE,Cochrane Library,CNKI,Wanfang,and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July 2022.Meta-analysis was performed using RevMan 5.3 software.RESULTS After screening according to the inclusion and exclusion criteria,6 articles were included,including 2 randomized controlled trials and 4 nonrandomized controlled trials,with a total of 575 patients included in the meta-analysis.The results showed that the objective response rate[odds ratio(OR)=2.56,95%confidence interval(CI):1.66-3.96,P<0.0001],disease control rate(OR=3.03,95%CI:1.88-4.89,P<0.00001),1-year survival rate(OR=3.79,95%CI:2.50-5.76,P<0.00001),2-year survival rate(OR=2.34,95%CI:1.43-3.85,P=0.0008),and 3-year survival rate(OR=3.34,95%CI:1.61-6.94,P=0.001)were all superior to those of the control group;the postoperative decrease in alpha-fetoprotein value(OR=295.53,95%CI:250.22-340.85,P<0.0001),the postoperative increase in CD4 value(OR=10.59,95%CI:8.78-12.40,P<0.00001),and the postoperative decrease in CD8 value(OR=6.47,95%CI:4.44-8.50,P<0.00001)were also significantly higher than those in the TACE-alone treatment group.CONCLUSION Compared with TACE-alone treatment,TACE+CRA combined treatment not only improves the immune function of HCC patients with a diameter of≥5 cm,but also enhances the therapeutic efficacy and long-term survival rate,without increasing the risk of complications.Therefore,TACE+CRA combined treatment may be a more recommended treatment for patients with HCC with a diameter of≥5 cm.

Systematic Analysis of Post-Translational Modifications for Increased Longevity of Biotherapeutic Proteins

Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins.

Modulatory role of plant-derived metabolites on host-microbiota interactions:personalized therapeutics outlook

A diverse array of microbes in and on the human body constitute the microbiota.These micro-residents continuously interact with the human host through the language of metabolites to dictate the host’s physiology in health and illnesses.Any biotic and abiotic component ensuring a balanced host-microbiota interaction are potential microbiome therapeutic agents to overcome human diseases.Plant metabolites are continually being used to treat various illnesses.These metabolites target the host’s metabolic machinery and host-gut microbiota interactions to overcome human diseases.Despite the paramount therapeutic significance of the factors affecting host-microbiota interactions,a comprehensive overview of the modulatory role of plant-derived metabolites in host-microbiota interactions is lacking.The current review puts an effort into comprehending the role of medicinal plants in gut microbiota modulation to mitigate various human illnesses.It would develop a holistic understanding of hostmicrobiota interactions and the role of effectors in health and diseases.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

A novel approach to Parkinson's disease treatment with a potentially dual-acting therapeutic agent that targetsα-synuclein aggregation and neuron death

Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy bodies.While the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.

Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.

Lactate:a prospective target for therapeutic intervention in psychiatric disease

Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs.Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte rs.Among these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years.Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant effect.In this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling molecule.In addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.