Targeting Cancer Mitochondria by Inducing an Abnormal Mitochondrial Unfolded Protein Response Leads to Tumor Suppression.

The mitochondrial unfolded protein response (UPRmt) is a pivotal cellular mechanism that ensures mitochondrial homeostasis and cellular survival under stress conditions. This study investigates the role of UPRmt in modulating the response of nasopharyngeal carcinoma cells to cisplatin-induced stress. We report that the inhibition of UPRmt via AEB5F exacerbates cisplatin cytotoxicity, as evidenced by increased lactate dehydrogenase (LDH) release and apoptosis, characterized by a surge in TUNEL-positive cells. Conversely, the activation of UPRmt with oligomycin attenuates these effects, preserving cell viability and reducing apoptotic markers. Immunofluorescence assays reveal that UPRmt activation maintains mitochondrial membrane potential and ATP production in the presence of cisplatin, countering the rise in reactive oxygen species (ROS) and inhibiting caspase-9 activation. These findings suggest that UPRmt serves as a cytoprotective mechanism in cancer cells, mitigating cisplatin-induced mitochondrial dysfunction and apoptosis. The data underscore the therapeutic potential of modulating UPRmt to improve the efficacy and reduce the side effects of cisplatin chemotherapy. This study provides a foundation for future research on the exploitation of UPRmt in cancer treatment, with the aim of enhancing patient outcomes by leveraging the cellular stress response pathways.

Involvement of lncRNAs in the regulation of aerobic glycolysis in hepatocellular carcinoma: Main functions, regulatory mechanisms and potential therapeutic implications (Review).

Even under aerobic conditions, tumor cells can reprogram their metabolism to preferentially metabolize glucose into lactic acid. This abnormal metabolic pattern, known as the 'Warburg' effect or aerobic glycolysis, promotes cancer progression. Long non­coding RNAs (lncRNAs) are RNAs that are >200 nucleotides in length and do not have protein­coding capabilities. However, these RNAs play a key role in tumor development. There is increasing evidence to indicate that lncRNAs regulate glucose metabolism in tumor cells by affecting metabolic enzymes and some signaling pathways, thereby regulating the occurrence and progression of hepatocellular carcinoma (HCC). Therefore, it is crucial to understand which lncRNAs play a regulatory role in HCC glycolysis and to determine the related molecular mechanisms. The present review summarized and discussed the functions of lncRNAs, focusing on the regulatory mechanisms of lncRNAs in the process of glycolysis in HCC. In addition, the present review suggests the importance of lncRNAs as future therapeutic targets for antitumor cell metabolism.

Altered functional connectivity in patients with post-stroke fatigue: A resting-state fMRI study.

BACKGROUND: Post-stroke fatigue (PSF) was a common complication after stroke. This study aimed to explore the neuroimaging mechanism of PSF, which was rarely studied. METHODS: Patients with the first episode of ischemic stroke were recruited from the First Affiliated Hospital of Wenzhou Medical University between March 2021 and December 2022. The fatigue severity scale (FSS) was used to assess fatigue symptoms. PSF was diagnosed by a neurologist based on the FSS score and PSF diagnostic criteria. All the patients were scanned by resting-state functional MRI (rs-fMRI). Precuneus, the posterior node of default-mode network (pDMN), was related to fatigue. Therefore, imaging data were further analyzed by the seed-based resting-state functional connectivity (FC) approach, with the left (PCUN.L) and right precuneus (PCUN.R) being the seeds. RESULTS: A total of 70 patients with acute ischemic stroke were finally recruited, comprising 40 patients with PSF and 30 patients without PSF. Both the PCUN.L and PCUN.R seeds (pDMN) exhibited decreased FC with the prefrontal lobes located at the anterior part of DMN (aDMN), and the FC values were negatively correlated with FSS scores (both p < 0.001). These two seeds also exhibited increased FC with the right insula, and the FC values were positively correlated with FSS scores (both p < 0.05). CONCLUSION: The abnormal FC between the aDMN and pDMN was associated with PSF. Besides, the insula, related to interoception, might also play an important role in PSF.

HIF-1α is an important regulator of IL-8 expression in human bone marrow stromal cells under hypoxic microenvironment.

The secretion of IL-8 has been found increasing for different reasons in human bone marrow stromal cells (BMSCs), resulting in poor prognosis in patients with hematologic neoplasms. Hypoxia, a typical feature of numerous hematologic neoplasms microenvironment, often produces hypoxia inducible factor-1α (HIF-1α) which stabilizes and promotes tumor progression. Besides, hypoxic conditions also induce IL-8 production in BMSCs. However, very little is known about the mechanism of increased IL-8 expression in BMSCs caused by hypoxia. In the present study, HIF-1α and IL-8 were found highly expressed in BMSC lines under hypoxic conditions. In addition, the expression and secretion of IL-8 were significantly inhibited by the knockdown of HIF-1α under hypoxic conditions. Furthermore, HIF-1α was found to transcriptionally regulate IL-8 by binding to the region of IL-8 promoter at - 147 to - 140. Collectively, these results demonstrate that IL-8's increase is partly due to the hypoxic microenvironment in hematologic neoplasms, and activation of HIF-1α in BMSCs contributes to the induction and transcriptional regulation of IL-8 expression.

The mediating role of sleep quality in the relationship between dispositional mindfulness and fatigue in Chinese nurses during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 epidemic in China, clinical nurses are at an elevated risk of suffering fatigue. This research sought to investigate the correlation between dispositional mindfulness and fatigue among nurses, as well as the potential mediation role of sleep quality in this relationship. METHODS: This online cross-sectional survey was performed from August to September 2022 to collect data from 2143 Chinese nurses after the re-emergence of COVID-19. The significance of the mediation effect was determined through a bootstrap approach with SPSS PROCESS macro. RESULTS: Higher levels of dispositional mindfulness were significantly negatively related to fatigue (r = -0.518, P < 0.001) and sleep disturbance (r = -0.344, P < 0.001). Besides, insufficient sleep was associated with fatigue (r = 0.547, P < 0.001). Analyses of mediation revealed that sleep quality mediated the correlation of dispositional mindfulness to fatigue (ß = -0.137, 95% Confidence Interval = [-0.156, -0.120]). CONCLUSIONS: In the post-COVID-19 pandemic era, Chinese nurses' dispositional awareness was related to the reduction of fatigue, which was mediated by sleep quality. Intervention strategies and measures should be adapted to improve dispositional mindfulness and sleep quality to reduce fatigue in nurses during the pandemic.

Procyanidin alleviates ferroptosis and inflammation of LPS-induced RAW264.7 cell via the Nrf2/HO-1 pathway.

Inflammation is a common occurrence in many medical conditions and is a natural defense mechanism of the human body. Ferroptosis, an iron-dependent form of cell death related to lipid peroxide build-up, has been found to be involved in inflammation. The anti-inflammatory effects of procyanidin, however, are not yet fully understood. Through network pharmacology and bioinformatics analysis, it was suggested that procyanidin could modulate ferroptosis and cause anti-inflammatory effects on RAW264.7 cells. This was further evidenced through molecular docking, molecular dynamics, and in vitro experiments. The results indicated that procyanidin could diminish inflammation in LPS-induced RAW264.7 cells by regulating ferroptosis via the Nrf2/HO-1/Keap-1 pathway. In conclusion, procyanidin supplementation might be an effective way to reduce inflammation by decreasing the release of inflammatory cytokines and suppressing ferroptosis.

mPGES-1 Inhibitor Discovery Based on Computer-Aided Screening: Pharmacophore Models, Molecular Docking, ADMET, and MD Simulations.

mPGES-1 is an enzyme, which, when activated by inflammatory factors, can cause prostaglandin E synthesis. Traditional non-steroidal anti-inflammatory drugs are capable of inhibiting prostaglandin production, yet they can also cause gastrointestinal reactions and coagulation disorders. mPGES-1, the enzyme at the conclusion of prostaglandin production, does not cause any adverse reactions when inhibited. Numerous studies have demonstrated that mPGES-1 is more abundant in cancerous cells than in healthy cells, indicating that decreasing the expression of mPGES-1 could be a potential therapeutic strategy for cancer. Consequently, the invention of mPGES-1 inhibitors presents a fresh avenue for the treatment of inflammation and cancer. Incorporating a database of TCM compounds, we collected a batch of compounds that had an inhibitory effect on mPGES-1 and possessed IC50 value. Firstly, a pharmacophore model was constructed, and the TCM database was screened, and the compounds with score cut-off values of more than 1 were retained. Then, the compounds retained after being screened via the pharmacodynamic model were screened for docking at the mPGES-1 binding site, followed by high-throughput virtual screening [HTVS] and standard precision [SP] and super-precision [XP] docking, and the compounds in the top 20% of the XP docking score were selected to calculate the total free binding energy of MM-GBSA. The best ten compounds were chosen by comparing their score against the reference ligand 4U9 and the MM-GBSA_dG_Bind score. ADMET analysis resulted in the selection of ten compounds, three of which had desirable medicinal properties. Finally, the binding energy of the target protein mPGES-1 and the candidate ligand compound was analyzed using a 100 ns molecular dynamics simulation of the reference ligand 4U9 and three selected compounds. After a gradual screening study and analysis, we identified a structure that is superior to the reference ligand 4U9 in all aspects, namely compound 15643. Taken together, the results of this study reveal a structure that can be used to inhibit mPGES-1 compound 15643, thereby providing a new option for anti-inflammatory and anti-tumor drugs.

Novel Long Noncoding RNAs, LINC01093 and MYLK-AS1, Serve as Potential Diagnostic and Prognostic Biomarkers or Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies worldwide. In this research, we aimed to identify long noncoding RNAs (lncRNAs) as biomarkers for HCC diagnosis and prognosis. lncRNA expression profiles were obtained from Gene Expression Omnibus and The Cancer Genome Atlas databases. The differentially expressed lncRNAs between HCC and adjacent tissues were analyzed with bioinformatic tools. Four lncRNAs with area under the curve of the receiver operating characteristic curve >0.9 were selected from both datasets. Univariate and Kaplan-Meier analyses were performed to obtain LINC01093, MYLK-AS1, and MCM3AP-AS1 as the optimal diagnostic and prognostic biomarkers. Finally, qPCR confirmed that LINC01093 and MYLK-AS1 were significantly differentially expressed in HCC and adjacent normal tissues. In general, we demonstrated that novel lncRNAs, LINC01093 and MYLK-AS1, could be used as potential diagnostic and prognostic biomarkers for HCC.

Red Blood Cell Distribution Width as a Potential Valuable Survival Predictor in Hepatitis B Virus-related Hepatocellular Carcinoma.

Objectives: Red blood cell distribution width (RDW) is a widely used clinical parameter recently deployed in predicting various cancers. This study aimed to evaluate the prognostic value of RDW in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods: We conducted a retrospective study of 745 patients with HBV-related HCC, 253 patients with chronic hepatitis B (CHB), and 256 healthy individuals to compare their hematological parameters and analyze their RDW levels. Potential risk factors for long-term all-cause mortality in patients with HBV-related HCC were predicted using Multivariate Cox regression. A nomogram was generated, and its performance was evaluated. Results: The RDW of patients with HBV-related HCC was significantly higher than that of those with CHB and healthy controls. In the former, splenomegaly, liver cirrhosis, larger tumor diameter, multiple tumor number, portal vein tumor thrombus, and lymphatic or distant metastasis were significantly increased, and the later the Child-Pugh grade and Barcelona clinic liver cancer stage, the higher the RDW. Furthermore, multivariate Cox regression analysis identified RDW as an independent risk factor for predicting long-term all-cause mortality in patients with HBV-related HCC. Finally, we successfully generated a nomogram incorporating RDW and validated its predictive ability. Conclusions: RDW is a potentially valuable hematological marker for predicting the survival and prognosis of patients with HBV-related HCC. The nomogram incorporating RDW can be used as an effective tool to plan the individualized treatment of such patients.

Analysis of Interpolation Methods in the Validation of Backscattering Coefficient Products.

Validation is the basis of synthetic aperture radar (SAR) image quantification applications. Based on the point target of the field site, the radiation characteristics of the backscattering coefficient image can be used to optimize the SAR imaging, and the product production system can be more closely targeted, to ensure the image product accuracy in the actual quantification application. In this study, the validation of the backscattering coefficient image was examined using calibrators, and the radiometric properties of the image were evaluated by extracting the radar cross-section of each point target. Bilinear interpolation and fast Fourier transform (FFT) interpolation methods were introduced for the local area interpolation of point targets, and the two methods were compared from the perspective of response function imaging and validation accuracy. The results show that the FFT interpolation method is more favorable for validating the backscattering coefficient.

Lactate Dehydrogenase Predicts Hemorrhagic Transformation in Patients with Acute Ischemic Stroke.

INTRODUCTION: Hemorrhagic transformation (HT) is a severe but frequent complication of acute ischemic stroke (AIS). This study aimed to evaluate the relationship between serum lactate dehydrogenase (LDH) levels and HT. METHODS: We retrospectively included 542 AIS patients with HT and 1,091 age- and gender-matched patients without HT. Demographic and clinical data were obtained from medical records, and blood samples were obtained within 24 h after admission. The characteristics of the groups were compared. With the receiver operating characteristic (ROC) curve analysis, we assessed the discriminating capacity of LDH levels in predicting HT in patients with AIS. The logistic regression model was used to determine the connection between LDH and HT. RESULTS: The HT group had considerably higher LDH levels than the non-HT group (263.0 [216.0-323.3] U/L versus 178.0 [162.0-195.0] U/L, p < 0.001). We also observed that the levels of LDH in the parenchymal hemorrhage subgroup were significantly higher than those in the hemorrhagic infarction subgroup (281.0 [230.0-340.0] U/L versus 258.0 [209.0-311.0] U/L, p < 0.001). The area under the ROC curve of LDH was 0.890 (95% confidence level [CI] 0.874-0.905, p < 0.001). Besides, logistic regression revealed that high LDH levels (LDH >215 U/L) showed a higher risk of HT (odds ratio = 10.958, 95% CI 7.964-15.078, p < 0.001). CONCLUSION: High LDH levels were linked with an increased risk of HT in AIS patients. Practical measures should be considered in patients with increased LDH levels (LDH >215 U/L).

Beneficial effects of Panax notoginseng (Burkill) F. H. Chen flower saponins in rats with metabolic hypertension by inhibiting the activation of the renin-angiotensin-aldosterone system through complement 3.

BACKGROUND: Metabolic hypertension (MH) has become the most common type of hypertension in recent years due to unhealthy eating habits and lifestyles of people, such as over-eating alcohol, high fat, and sugar diets (ACHFSDs). Therefore, effective means to combat MH are needed. Previous studies have shown that Panax notoginseng (Burkill) F. H. Chen flower saponins (PNFS) can lower blood pressure in spontaneously hypertensive rats (SHR). However, whether it acts on MH and its mechanism of action remain unclear.  METHODS: The pharmacodynamic effects of PNFS were evaluated in rats with ACHFSDs-induced MH. The blood pressure, blood biochemical, grip strength, face temperature, vertigo time, and liver index were estimated. The histological changes in the liver and aorta were observed using hematoxylin and eosin staining. The levels of ET-1, TXB2, NO, PGI2, Renin, ACE, Ang II, and ALD in plasma were detected using ELISA. The levels of C3, KLF5, LXRα, and Renin in kidney tissues were measured using qRT-PCR.The expression levels of C3, KLF5, LXRα, and Renin in kidney tissues were examined using Western blotting. RESULTS: In the present study, PNFS was found to reduce blood pressure, face temperature, and vertigo time, increase grip strength and improve dyslipidemia in rats with MH. In addition, PNFS decreased the plasma levels of ET-1 and TXB2, elevated the levels of NO and PGI2, and improved pathological aortic injury. Meanwhile, PNFS decreased the plasma levels of Renin, ACE, Ang II, and ALD. QRT-PCR and Western bolt showed that PNFS downregulated C3, KLF5, LXRα, and Renin protein and mRNA expression in the kidneys of rats with MH. CONCLUSION: The finding of the present study suggested that PNFS could downregulate C3 and KLF-5 expression in rats with MH, thereby inhibiting the overactivation of the renin-angiotensin-aldosterone system, while improving vascular endothelial function and ultimately reducing blood pressure in rats with MH.

Anaerobic-anoxic-oxic biological treatment of high-strength, highly recalcitrant polyphenylene sulfide wastewater.

This paper outlines an integrated anaerobic-anoxic-oxic (A2O) treatment scheme for high-strength, highly recalcitrant wastewater from the production of polyphenylene sulfide (PPS) resins and their composite chemicals. An integrated anaerobic granular sludge blanket (GSB) and anoxic-oxic (AO) reactor indicated that the A2O removed chemical oxygen demand (COD) of up to 7,043 mg/L with no adverse impact from high total dissolved solids (25,000 mg/L) on the GSB COD removal and effluent suspended solids. At a Total Kjeldahl Nitrogen (TKN) nitrification load of 0.11 g TKN/L.d and 400 mg NH3/L, almost 99 % of the NH3 was degraded with effluent NH3 < 5 mg/L, meeting the limit of 35 mg/L. High S2- levels of up to 1470 mg/L can be transformed through aerobic microbial degradation to meet a limit of 1.0 mg/L. With proper microbial acclimation and process designs, the integrated A2O scheme offers a resilient and robust treatment for high-strength recalcitrant PPS wastewater.

Predictive Ability of Systemic Inflammation Response Index for the Risk of Pneumonia in Patients with Acute Ischemic Stroke.

INTRODUCTION: Several studies have examined the crucial role of inflammatory indexes such as the ratio of monocyte and lymphocyte (MLR), systemic-immune-inflammation-index, and the ratio of neutrophil and lymphocyte (NLR) in stroke-associated pneumonia (SAP). However, the function of the systemic inflammation response index (SIRI) in SAP is not known. This study investigated whether SIRI at admission could predict the incidence of SAP in patients with acute ischemic stroke (AIS). PATIENTS AND METHODS: 2,802 AIS patients collected from 2013 to 2021 were divided into the SAP and non-SAP groups. The predictive performance of SIRI in SAP was evaluated by the receiver operating characteristic curve. Multivariate regression analysis and the restricted cubic spline (RCS) were performed to explore the relationship between SIRI and SAP risk. RESULTS: The SIRI at admission in SAP patients was significantly higher than that in non-SAP patients (median [IQR]: 3.75 [2.05, 6.99] vs. 1.51 [0.94, 2.62], p < 0.001). SIRI had a predictive ability for predicting the incidence of SAP with area under the curve of 0.757, better than NLR and MLR (both p < 0.05). SIRI ≥2.74 was an independent risk factor for the incidence of SAP (odds ratio: 5.82, 95% confidence interval: 4.54, 7.49, p < 0.001). The RCS model showed an increasing trend of the SAP risk with the increase of SIRI. CONCLUSION: SIRI showed a good predictive value for SAP. In clinical practice, AIS patients with high SIRI levels (SIRI ≥2.74) should be aware of the risk of SAP.

Arsenic adsorption by different Fe-enriched biochars conditioned with sulfuric acid.

In this study, ferric chloride and sulfuric acid were used to increase the Fe-containing minerals on the biochar surface before a pyrolysis at 600 °C. The pristine and Fe-modified biochars prepared at different concentrations of sulfuric acid (50FBC and 72FBC) were characterized and analyzed, and their capacity of As(V) adsorption under various pH and ionic strength were evaluated. The results showed that the maximum adsorption capacities of As(V) calculated by the Langmuir model for 50FBC and 72FBC are 10.33 and 15.61 mg g-1, respectively, which are enhanced by 5.0 and 7.8 times compared with the pristine biochar. The higher dosage of H2SO4 (72%) used in the modification leads to a better adsorption capacity of As, especially under neutral to alkaline conditions (7.0 < pH < 10.0). It might result from the increased amounts of Fe-containing minerals formed on the biochar surface, and the enriched functional groups such as phenolic hydroxyl and carboxyl, resulting in the resistance to alkaline conditions. Overall, the Fe-modified biochar, especially 72FBC, had good potential as an environmentally friendly adsorbent for removing As from contaminated water under a wider pH range.

Clinical significance of albumin to globulin ratio among patients with stroke-associated pneumonia.

Background: It has been proven that the ratio of albumin to globulin (A/G) is a typical biomarker for monitoring inflammation and nutritional status. But the potential role of A/G in stroke-associated pneumonia (SAP) after acute ischemic stroke (AIS) remained unknown. Patients and methods: Following inclusion criteria, 5,173 AIS patients were included and segmented into SAP (n = 897) and non-SAP (n = 4,276) groups. The differences in variables between groups were compared. The logistic regression model was used to determine the association between A/G and SAP, and a forest plot was drawn. Results: Compared with the non-SAP group, the SAP group had a lower A/G level (P < 0.001). Then, A/G was divided into quartiles. In comparison to Q3 (A/G = 1.25-1.39), logistic regression revealed that patients with a lower A/G (A/G ≤ 1.09) had a higher risk of SAP (OR = 1.96, 95% CI, 1.56-2.46, P < 0.001). On the contrary, those with a higher A/G (A/G ≥ 1.4) had a lower SAP risk (OR = 0.73, 95% CI, 0.54-0.97, P = 0.029). Conclusion: The study revealed that a low A/G level was associated with an increased SAP risk. Appropriate preventative measures for SAP should be taken in AIS patients with a low A/G level.

Glucose to Platelet Ratio: A Potential Predictor of Hemorrhagic Transformation in Patients with Acute Ischemic Stroke.

Glucose and platelet are two easily obtained clinical indicators; the present research aimed to demonstrate their association with hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients without thrombolytic or thrombectomy therapy. This was a single-center retrospective study. Patients who were diagnosed with HT after AIS were included in the HT group. Meanwhile, using the propensity score matching (PSM) approach, with a ratio of 1:2, matched patients without HT were included in the non-HT group. Serum G/P levels were measured on the first morning after admission (at least eight hours after the last meal). Characteristics were compared between the two groups. Multivariate logistic regression was used to determine the independent relationship between G/P and HT after AIS, with G/P being divided into quartiles. From January 2013 to March 2022, we consecutively included 643 AIS patients with HT (426/643 [66.25%] with HI and 217/643 [33.75%] with PH), and 1282 AIS patients without HT, at the First Affiliated Hospital of Wenzhou Medical University. The HT group had higher G/P levels than the non-HT group (0.04 ± 0.02 vs. 0.03 ± 0.02, p < 0.001). However, there was no difference in G/P levels between HI and PH subgroups (0.04 ± 0.02 vs. 0.04 ± 0.02, p > 0.05). Moreover, the G/P levels were divided into quartiles (Q1 ≤ 0.022; Q2 = 0.023−0.028; Q3 = 0.029−0.039; Q4 ≥ 0.040), with Q1 being settled as the reference layer. After controlling the confounders, multivariate regression analyses showed that the Q4 layer (Q4: G/P ≥ 0.040) was independently associated with elevated HT risk (odds ratio [OR] = 1.85, 95% CI = 1.31−2.63, p < 0.001). G/P levels on admission were independently associated with HT risk in AIS patients. In clinical practice, adequate attention should be paid to AIS patients with elevated G/P levels (G/P ≥ 0.040).

Anti-Freezing Nanocomposite Organohydrogels with High Strength and Toughness.

Hydrogels based on nanocomposites (NC) structure have acquired a great deal of interest, but they are still limited by relatively low mechanical strength, inevitably losing elasticity when applied below subzero temperatures, due to the formation of ice crystallization. In this study, an anti-freezing and mechanically strong Laponite NC organohydrogel was prepared by a direct solvent replacement strategy of immersing Laponite NC pre-hydrogel into ethylene glycol (EG)/water mixture solution. In the organohydrogel, a part of water molecules was replaced by EG, which inhibited the formation of ice crystallization even at extremely low temperatures. In addition, the formation of hydrogen bonds between Laponite and the monomers of N-isopropylacrylamide (NIPAM) and hydroxyethyl acrylate (HEA) endowed the organohydrogels with high mechanical strength and toughness. The NC organohydrogel can maintain its mechanical flexibility even at -25 °C. The compressive stress, tensile stress, and elongation at the break of N5H5L reached 3871.71 kPa, 137.05 kPa, and 173.39%, respectively, which may be potentially applied as ocean probes in low temperature environment.

Neurotransmitters: Potential Targets in Glioblastoma.

For decades, glioblastoma multiforme (GBM), a type of the most lethal brain tumor, has remained a formidable challenge in terms of its treatment. Recently, many novel discoveries have underlined the regulatory roles of neurotransmitters in the microenvironment both physiologically and pathologically. By targeting the receptors synaptically or non-synaptically, neurotransmitters activate multiple signaling pathways. Significantly, many ligands acting on neurotransmitter receptors have shown great potential for inhibiting GBM growth and development, requiring further research. Here, we provide an overview of the most novel advances concerning the role of neurotransmitters in the normal neural and the GBM microenvironments, and discuss potential targeted drugs used for GBM treatment.