A scientometric analysis of immunotherapies for gliomas: Focus on GBM.

Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being the most common and aggressive type. The standard therapy for GBM has remained unchanged for nearly two decades, with no significant improvement in survival outcomes. Despite several barriers such as the tumor microenvironment (TME) and blood-brain barrier, immunotherapies bring new hope for the treatment of GBM. To better understand the development and progress of immunotherapies in GBM, we made this scientometric analysis of this field. A total of 3753 documents were obtained from the Web of Science Core Collection, with publication years ranging from 1999 to 2022. The Web of Science platform, CiteSpace, and VOS viewer were used to conduct the scientometric analysis. The results of scientometric analysis showed that this field has recently become a popular topic of interest. The United States had the most publications among 89 countries or regions. Keyword analysis indicated significant areas in the field of immunotherapies for GBM, especially TME, immune checkpoint blockades (ICBs), chimeric antigen receptor T (CAR-T) cells, vaccines, and oncolytic viruses (OVs). Overall, we hope that this scientometric analysis can provide insights for researchers and promote the development of this field.

Taxifolin inhibits melanoma proliferation/migration impeding USP18/Rac1/JNK/ß-catenin oncogenic signaling.

BACKGROUND: Metastatic melanoma is a fatal cancer. Despite the advances in targeted therapy and immunotherapy for patients with melanoma, drug resistance and low response rates pose a considerable challenge. Taxifolin is a multifunctional natural compound with emerging antitumor potentials. However, its utility in melanoma treatment remains unclear. PURPOSE: The study aimed to investigate the effect of purified Taxifolin from Larix olgensis roots (Changbai Mountain, China) on melanoma and explore the underlying mechanism. METHODS: Purified Taxifolin from Larix olgensis roots was evaluated for its antimelanoma effects in vitro and in vivo settings. RNA-seq analysis was performed to explore the underlying mechanism. RESULTS: Purified Taxifolin (> 99 %) from Larix olgensis roots inhibited the proliferation and migration of B16F10 melanoma cells at 200 and 400 µM, and of A375 cells at 100 and 200 µM. Taxifolin administered at 60 mg/kg suppressed tumor growth and metastasis in mouse models without causing significant toxicity. Taxifolin modulated USP18/Rac1/JNK/ß-catenin axis to exert its antitumor effect. CONCLUSION: These findings indicate that Taxifolin derived from Larix olgensis roots may be a promising antimelanoma therapy.

STING in tumors: a focus on non-innate immune pathways.

Cyclic GMP-AMP synthase (cGAS) and downstream stimulator of interferon genes (STING) are involved in mediating innate immunity by promoting the release of interferon and other inflammatory factors. Mitochondrial DNA (mtDNA) with a double-stranded structure has greater efficiency and sensitivity in being detected by DNA sensors and thus has an important role in the activation of the cGAS-STING pathway. Many previous findings suggest that the cGAS-STING pathway-mediated innate immune regulation is the most important aspect affecting tumor survival, not only in its anti-tumor role but also in shaping the immunosuppressive tumor microenvironment (TME) through a variety of pathways. However, recent studies have shown that STING regulation of non-immune pathways is equally profound and also involved in tumor cell progression. In this paper, we will focus on the non-innate immune system pathways, in which the cGAS-STING pathway also plays an important role in cancer.

Efficacy and safety of innate and adaptive immunotherapy combined with standard of care in high-grade gliomas: a systematic review and meta-analysis.

Background: Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival. Method: Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356). Results: We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; Z = -2.00, P = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; Z = -1.99, P = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; P = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; Z = -3.53; P = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; Z = -2.23; P = 0.0256). Conclusion: Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.

Histone chaperone SSRP1 is required for apoptosis inhibition and mitochondrial function in HCC via transcriptional promotion of TRAP1.

Epigenetic regulation contributes to human health and disease, especially cancer, but the mechanisms of many epigenetic regulators remain obscure. Most research is focused on gene regulatory processes, such as mRNA translation and DNA damage repair, rather than the effects on biological functions like mitochondrial activity and oxidative phosphorylation. Here, we identified an essential role for the histone chaperone structure-specific recognition protein 1 (SSRP1) in mitochondrial oxidative respiration in hepatocellular carcinoma, and found that SSRP1 suppression led to mitochondrial damage and decreased oxidative respiration. Further, we focused on TNF receptor-associated protein 1 (TRAP1), the only member of the heat shock protein 90 (HSP90) family, which directly interacts with selected respiratory complexes and affects their stability and activity. We confirmed that SSRP1 downregulation caused a decrease in TRAP1 expression at both the mRNA and protein levels. A chromatin immunoprecipitation assay also showed that SSRP1 could deposit in the TRAP1 promoter region, indicating that SSRP1 maintains mitochondrial function and reactive oxygen species levels through TRAP1. Additionally, rescue experiments and animal experiments confirmed the mechanism of SSRP1 and TRAP1 interaction. In summary, we identified a new mechanism that connects mitochondrial respiration and apoptosis, via SSRP1.

Stat3 shRNA delivery with folate receptor-modified multi-functionalized graphene oxide particles for combined infrared radiation and gene therapy in hepatocellular carcinoma.

As a vital oncogene, a variety of inhibitors targeting Stat3 and its various upstream signaling pathways has been explored. Since small molecules, peptidomimetics and other peptide inhibitors usually lead to side effects and difficult administration, gene therapeutics that have characteristics of low toxicity and high targeting, make them an attractive alternative for targeting Stat3. A major challenge to this approach is the lack of safe delivery systems for in-vivo applications. Among the various siRNA delivery systems, nanoparticles emerge as a new tool for gene delivery with high biocompatibility, low cost, and minimal toxicity. In this study, we developed a graphene oxide (GO)-based nanocarrier, GO-polyethyleneimine (PEI)-polyethylene glycol (PEG)-folic acid (FA), as a tool targeting for Stat3-specific shRNA to mouse hepatoma cells in vitro and in vivo . Infrared photothermal therapy was combined in vivo since GO has the characteristic of infrared absorbability. Our results suggest a significant tumor growth inhibition after treatment with GO-PEI-PEG-FA- sh-Stat3 combined with infrared photothermal therapy. Thus, GO-PEI-PEG-FA appears to be a novel nano-transformer that could be used in the clinics in future.

[Preliminary study of Ilizarov technique in treatment of lower limb deformity caused by achondroplasia].

Objective: To investigate the surgical method and preliminary effectiveness of Ilizarov technique in the treatment of lower limb deformity caused by achondroplasia. Methods: The clinical data of 38 patients with lower limb deformity caused by achondroplasia treated by Ilizarov technique between February 2014 and September 2021 were retrospectively analyzed. There were 18 males and 20 females, the age ranged from 7 to 34 years, with an average of 14.8 years. All patients presented with bilateral knee varus deformity. The preoperative varus angles was (15.2±4.2)°, and knee society score (KSS) was 61.8±7.2. Nine of these patients underwent tibia and fibula osteotomy, 29 cases underwent tibia and fibula osteotomy and bone lengthening at the same time. Full-length bearing position X-ray films of bilateral lower limbs were taken to measure the bilateral varus angles, analyze the healing index, and record the occurrence of complications. KSS score was used to evaluate the improvement of knee joint function before and after operation. Results: All 38 cases were followed up 9-65 months, with an average of 26.3 months. Needle tract infection occurred in 4 cases and needle tract loosening occurred in 2 cases after operation, which were improved after symptomatic treatment such as dressing change, Kirschner wire change, and oral antibiotics, and no neurovascular injury occurred in all patients. The external fixator was worn for 3-11 months after operation, with an average of 7.6 months, and the healing index was 43-59 d/cm, with an average of 50.3 d/cm. At last follow-up, the leg was 3-10 cm longer, with an average of 5.5 cm. The varus angles was (1.5±0.2)° and the KSS score was 93.7±2.6, which significantly improved when compared with those before operation ( P<0.05). Conclusion: Ilizarov technique is a safe and effective method for the treatment of short limb with genu varus deformity caused by achondroplasia, which can improve the quality of life of patients.

[Clinical characteristics analysis of 22 062 patients of foot and ankle deformity from QIN Sihe Orthopaedic Surgery Database between May 25, 1978 and December 31, 2020].

Objective: Based on the clinical data of patients with foot and ankle deformities in the QIN Sihe Orthopaedic Surgery Database, to analyze the characteristics and treatment strategies of foot and ankle deformities, and provide a basis for clinical decision-making. Methods: A total of 22 062 patients with foot and ankle deformities who received orthopedic surgery between May 25, 1978 and December 31, 2020 were searched in the QIN Sihe Orthopedic Surgery Database. The gender, age at operation, regional distribution, etiology, type of deformity, operation method, postoperative fixation method, and other information were collected. Results: Among the 22 062 patients, there were 13 046 males (59.13%) and 9 016 females (40.87%); the age at operation ranged from 1 to 77 years, with a median of 17 years, and 20 026 cases (90.77%) were aged 5 to 40 years. The patients came from 32 provinces, municipalities, and autonomous regions across the China and 5 countries including India and the United States, et al. The etiology and diseases type covered 154 kinds (of which sequelae of poliomyelitis, cerebral palsy, spina bifida and tethered spinal cord, congenital equinovarus foot, post-traumatic foot and ankle deformity, and Charcot-Marie-Tooth disease accounted for the highest proportion). The types of deformities included varus foot, equinus foot, valgus foot, talipes calcaneus, equinocavus, high arched foot, claw toe, and flail foot. Surgical methods included tendon lengthening, soft tissue release, tendon transposition, osteotomy orthopedics, and ankle arthrodesis. The 36 620 operations were performed, including 11 561 cases of hip, knee, and lower leg operations to correct the foot and ankle deformities. Postoperative fixation methods included Ilizarov external fixator in 2 709 cases (12.28%), combined external fixator in 3 966 cases (17.98%), and plaster or brace fixation in 15 387 cases (69.74%). Conclusion: Male patients with foot and ankle deformities account for a large proportion, and the population distribution is mainly adolescents, with a wide distribution of regions, causes and diseases, and talipes equinovarus and varus foot are the main types of deformities. Foot and ankle deformities are often combined with deformities of other parts of the lower limb, which requires a holistic treatment concept. The application of foot soft tissue and bone surgery combined with Ilizarov external fixator and combined external fixators provides a guarantee for the correction of complex foot and ankle deformities.

[Analysis on the characteristics of 837 patients with post-traumatic lower limb deformities from QIN Sihe Orthopaedic Surgery Database between May 25, 1978 and December 31, 2020].

Objective: To summarize and analyze the characteristics and treatment strategies of post-traumatic lower limb deformity based on QIN Sihe Orthopaedic Surgery Database. Methods: A clinical data of 837 patients with post-traumatic lower limb deformities treated by orthopaedic surgery between May 25, 1978 and December 31, 2020 in QIN Sihe Orthopaedic Surgery Database were analyzed retrospectively. The information of the patient's gender, age at the time of surgery, region of origin, cause of trauma, deformity side, orthopedic surgery related information (operation time, location, type, and fixation method after operation) were summarized and analyzed. Results: All patients came from 32 provinces, municipalities, autonomous regions, and Taiwan in China. Among them, 551 cases (65.83%) were male and 286 cases (34.17%) were female. The age of the patients at the time of surgery was 3-84 years old, with an average of 27.6 years old, and the most patients were 16-45 years old (559 cases, 66.78%). The main cause of trauma was traffic accident injury (639 cases, 76.34%). The deformity mainly involved unilateral limbs, including 394 cases (47.07%) on the left side and 376 cases (44.92%) on the right side. The most patients were admitted between 2008 and 2017, accounting for 53.05% (444/837). All patients were operated on one or more sites (1 048 sites), among which ankle and toe surgery were the most, accounting for 48.38% (507/1 048). The patients received 1204 surgeries including tendon lengthening and soft tissue contracture release, et al. Orthopedic surgery combined with bone external fixation was used in 624 cases (467 cases of Ilizarov external fixation and 157 cases of combined external fixation), and plaster or brace external fixation was used in 213 cases. Conclusion: Post-traumatic lower extremity deformity patients have a large proportion of males, with a wide geographical distribution, involving various parts of the lower extremities, and most commonly in the foot and ankle. Orthopedic surgery combined with bone external fixation (Ilizarov technique) is the main methods for correction and functional reconstruction of post-traumatic lower limb deformity.

RSL3 triggers glioma stem cell differentiation via the Tgm2/AKT/ID1 signaling axis.

RSL3 is a synthetic molecule that inactivates glutathione peroxidase 4 to induce ferroptosis. However, its effect on glioma stem cells (GSC) remains unclear. In this study, we found that RSL3 significantly suppressed GSC proliferation and induced their differentiation into astrocytes, which was accompanied by the downregulation of stemness-related markers, including Nestin and Sox2. Combined transcriptome and proteome analyses further revealed that RSL3 promoted GSC differentiation by suppressing transglutaminase 2 (Tgm2), but not by ferroptosis-related pathways. Tgm2 overexpression in CSC2078 cells rescued the changes in stemness-related markers and differentiation caused by RSL3, which was mediated by inhibitor of DNA binding 1 (ID1) activation. Further studies identified ID1 as a downstream signaling target of Tgm2. Blocking the phosphoinositide-3 kinase (PI3K)/Akt pathway with LY294002 suppressed PI3K, p-Akt, and ID1 levels but not Tgm2. Tgm2 overexpression abrogated the changes in PI3K, p-Akt, and ID1 levels caused by LY294002. Taken together, we demonstrate that RSL3 does not induce ferroptosis; instead, it inhibits GSC proliferation and triggers their differentiation by suppressing the Tgm2/Akt/ID1 signaling axis.

Non-Negative Matrix Factorization Based on Smoothing and Sparse Constraints for Hyperspectral Unmixing.

Hyperspectral unmixing (HU) is a technique for estimating a set of pure source signals (end members) and their proportions (abundances) from each pixel of the hyperspectral image. Non-negative matrix factorization (NMF) can decompose the observation matrix into the product of two non-negative matrices simultaneously and can be used in HU. Unfortunately, a limitation of many traditional NMF-based methods, i.e., the non-convexity of the objective function, may lead to a sub-optimal solution. Thus, we put forward a new unmixing method based on NMF under smoothing and sparse constraints to obtain a better solution. First, considering the sparseness of the abundance matrix, a weight sparse regularization is introduced into the NMF model to ensure the sparseness of the abundance matrix. Second, according to the similarity prior of the same feature in the adjacent pixels, a Total Variation regularization is further added to the NMF model to improve the smoothness of the abundance map. Finally, the signatures of each end member are modified smoothly in spectral space. Moreover, it is noticed that discontinuities may emerge due to the removal of noisy bands. Therefore, the spectral data are piecewise smooth in spectral space. Then, in this paper, a piecewise smoothness constraint is further applied to each column of the end-member matrix. Experiments are conducted to evaluate the effectiveness of the proposed method based on two different datasets, including a synthetic dataset and the real-life Cuprite dataset, respectively. Experimental results show that the proposed method outperforms several state-of-the-art HU methods. In the Cuprite hyperspectral dataset, the proposed method's Spectral Angle Distance is 0.1694, compared to the TV-RSNMF method's 0.1703, L1/2NMF method's 0.1925, and VCA-FCLS method's 0.1872.

Epigenetic regulation of cancer stem cells: Shedding light on the refractory/relapsed cancers.

The resistance to drugs, ability to enter quiescence and generate heterogeneous cancer cells, and enhancement of aggressiveness, make cancer stem cells (CSCs) integral part of tumor progression, metastasis and recurrence after treatment. The epigenetic modification machinery is crucial for the viability of CSCs and evolution of aggressive forms of a tumor. These mechanisms can also be targeted by specific drugs, providing a promising approach for blocking CSCs. In this review, we summarize the epigenetic regulatory mechanisms in CSCs which contribute to drug resistance, quiescence and tumor heterogeneity. We also discuss the drugs that can potentially target these processes and data from experimental and clinical studies.

The Current Status of SSRP1 in Cancer: Tribulation and Road Ahead.

Methods: We search PubMed and Web of Sciences with keywords "SSRP1" and "Cancer." Only English literature was included, and conference papers and abstract were all excluded. Results: Transcription factors are classified into three groups based on their DNA binding motifs: simple helix-loop-helix (bHLH), classical zinc fingers (ZF-TFs), and homeodomains. The tumor-suppressive miR-497 (microRNA-497) acted as an undesirable regulator of SSRP1 upregulation, which led to tumor growth. The siRNA (small interfering RNA) knockdown of SSRP1 hindered cell proliferation along with incursion and glioma cell migration. Through the AKT (also known as protein kinase B) signaling pathway, SSRP1 silencing affected cancer apoptosis and cell proliferation. Conclusion: The MAPK (mitogen-activated protein kinase) signaling pathway's phosphorylation was suppressed when SSRP1 was depleted. The effect of curaxins on p53 and NF-B (nuclear factor-κB), and their toxicity to cancer cells, is attributable to the FACT (facilitates chromatin transcription) complex's chromatin trapping.

Roles for the methyltransferase SETD8 in DNA damage repair.

Epigenetic posttranslational modifications are critical for fine-tuning gene expression in various biological processes. SETD8 is so far the only known lysyl methyltransferase in mammalian cells to produce mono-methylation of histone H4 at lysine 20 (H4K20me1), a prerequisite for di- and tri-methylation. Importantly, SETD8 is related to a number of cellular activities, impinging upon tissue development, senescence and tumorigenesis. The double-strand breaks (DSBs) are cytotoxic DNA damages with deleterious consequences, such as genomic instability and cancer origin, if unrepaired. The homology-directed repair and canonical nonhomologous end-joining are two most prominent DSB repair pathways evolved to eliminate such aberrations. Emerging evidence implies that SETD8 and its corresponding H4K20 methylation are relevant to establishment of DSB repair pathway choice. Understanding how SETD8 functions in DSB repair pathway choice will shed light on the molecular basis of SETD8-deficiency related disorders and will be valuable for the development of new treatments. In this review, we discuss the progress made to date in roles for the lysine mono-methyltransferase SETD8 in DNA damage repair and its therapeutic relevance, in particular illuminating its involvement in establishment of DSB repair pathway choice, which is crucial for the timely elimination of DSBs.

Ilizarov technology in China: a historic review of thirty-one years.

PURPOSE: To summarize the evolution of Ilizarov technology in China, highlight important milestones, introduce the atmosphere of the era concerning the first uses and development of this technology, and share Chinese modification and experience in this field. METHOD: A thorough interview with senior ASAMI members of China and literature search and physical books in libraries was undertaken to summarize the history of Ilizarov technology in China. RESULTS: The formal development of Ilizarov technology began when professor Ilizarov himself came to Beijing (1991) and gave a speech. In the following 31 years, his technology was rapidly developed through China, with many symposiums held and associations established including ASAMI China (2003) and ILLRS China (2015). Today, Ilizarov technology has become the main treatment of complex fractures, defects, nonunion, infections, deformities, and chronic ischemic ulcers of the limbs. In those years, Chinese scholars also developed some special treatment methods and made many modifications to Ilizarov external fixators. CONCLUSION: Ilizarov technology has developed in China for 31 years. It revolutionized the treatment of complex limb traumas, deformities, and diseases. In the treatment of millions of patients, Chinese scholars had many unique experiences and made modifications to this technology which is worthy to share with the world.

[Preliminary analysis of the clinical characteristics of 1 012 patients with secondary lower limb deformity of spina bifida from QIN Sihe Orthopedic Surgery Case Data between October 12, 1986 and December 31, 2020].

OBJECTIVE: To analyze the characteristics of patients with secondary lower limb deformity of spina bifida based on the QIN Sihe Orthopedic Surgery Case Data, and provide the references for clinical research, diagnosis, and treatment. METHODS: A clinical data of 1 012 patients with secondary lower limb deformity of spina bifida between October 12, 1986 and December 31, 2020 selected from QIN Sihe Orthopedic Surgery Case Data was retrospectively analyzed. Among them, 231 cases (22.83%) had undergone orthopedic surgery for lower extremity deformities in other hospitals. The gender, age at surgery, indicators related to spina bifida (deformity side, comorbidity, sensory disturbance level), and information related to surgery (operating time, surgical site, postoperative fixation method) were analyzed. RESULTS: Of the 1012 patients, 457 were males and 555 were females. The age was 3-51 years at the time of surgery, with a median of 18.0 years; among them, the 15-30 years old group had the most patients, accounting for 53.16%. Most deformities involved both lower limbs (652 cases, 64.43%). There were 111 cases of ulcers in the weight-bearing area of the foot, 265 cases of gatism, 554 cases of sensory disturbance, and 85 cases of abnormal hair on the waist. From 2010 to 2019, there were significantly more patients undergoing surgery than before 2010, reaching 61.17%. Sensory disturbances mostly occurred in the ankle and foot. A total of 1 149 sites were treated with surgery, of which the most ankle joint deformities were corrected by surgery, accounting for 84.33%. The main fixation methods after orthopedic surgery were external fixation, including Ilizarov external fixation (442 cases), combined external fixation (315 cases), and plaster fixation (189 cases). CONCLUSION: Spina bifida can be secondary to severe deformities of the lower limbs, mainly in the ankles. Common complications include ulcers in the weight-bearing area, dysfunction of urine and feces, and sensory disturbances; external fixation is the main method of fixation after surgery.

GRIM-19 inhibits proliferation and induces apoptosis in a p53-dependent manner in colorectal cancer cells through the SIRT7/PCAF/MDM2 axis.

Colorectal cancer (CRC) is the leading deadly cancer worldwide. Gene associated with retinoid-IFN-induced mortality-19 (GRIM-19), a novel tumor suppressor, has been reported to be expressed at low levels in human CRC. However, the role of GRIM-19 in CRC progression and the corresponding detailed mechanisms are unclear. The results of this study indicated that GRIM-19 expression is related to CRC progression. Overexpression of GRIM-19 was found to inhibit CRC cell proliferation and induce apoptosis in vitro and in vivo. Our results demonstrated that GRIM-19 suppresses CRC through posttranslational regulation of p53, in which SIRT7 is activated by GRIM-19 and triggers PCAF-mediated MDM2 ubiquitination, eventually stabilizing the p53 protein. We also observed that GRIM-19 enhances the effect of oxaliplatin against CRC. In conclusion, GRIM-19 plays an important role in CRC development and is a potential biomarker and therapeutic target for clinical treatment of CRC.

RSL3 enhances the antitumor effect of cisplatin on prostate cancer cells via causing glycolysis dysfunction.

The resistance to cisplatin (DDP) and dose-related toxicity are the two important obstacles in the chemotherapy of prostate cancer (PCa) patients. The present study demonstrated that cotreatment of DDP and RSL3, a type of small molecular compound which can inactivate glutathione peroxidase 4 (GPX4) and induce ferroptosis, synergistically inhibited the viability and proliferation of PCa cells in vitro and in vivo at low dose. In vitro studies revealed that RSL3 improved that sensitivity of PCa cells to DDP by producing ROS and aggravating the cell cycle arrest and apoptosis caused by DDP. Mechanistically, RSL3 could decrease the ATP and pyruvate content as well as the protein levels of HKII, PFKP, PKM2, which indicated that RSL3 induced glycolysis dysfunction in prostate cancer cells. Rescuing RSL3-induced glycolysis dysfunction by supplement of exterior sodium pyruvate not only inhibited RSL3/DDP-induced changes of apoptosis-related proteins levels, but also mitigated the cell death caused by RSL3/DDP. In vivo studies further confirmed that cotreatment of RSL3 and DDP at low dose significantly inhibited the growth of PCa with no obvious side effects. Taken together, we demonstrated that RSL3 improved the sensitivity of PCa to DDP via causing glycolysis dysfunction. Our findings indicated that DDP-based chemotherapy combined with RSL3 might provide a promising therapy for PCa.

Perspectives on Oncolytic Salmonella in Cancer Immunotherapy-A Promising Strategy.

Since the first reported spontaneous regression of tumors in patients with streptococcus infection, cancer biological therapy was born and it evolved into today's immunotherapy over the last century. Although the original strategy was unable to impart maximal therapeutic benefit at the beginning, it laid the foundations for the development of immune checkpoint blockade and CAR-T which are currently used for cancer treatment in the clinics. However, clinical applications have shown that current cancer immunotherapy can cause a series of adverse reactions and are captious for patients with preexisting autoimmune disorders. Salmonellae was first reported to exert antitumor effect in 1935. Until now, numerous studies have proved its potency as an antitumor agent in the near future. In this review, we summarize the currently available data on the antitumor effects of Salmonella, and discussed a possibility of integrating Salmonella into cancer immunotherapy to overcome current obstacles.

The effects of tacrolimus plus phototherapy in the treatment of vitiligo: a meta-analysis.

The objective of this meta-analysis was performed to compare the effects of tacrolimus plus phototherapy in the treatment of patients with vitiligo. Relevant studies were identified by searching PubMed, Embase, and Web of Science databases. The main outcomes of interest included excellent response (≥ 75% repigmentation), good response (50-75% repigmentation), moderate response (25%-50% repigmentation), and poor response (< 25% repigmentation). Risk ratio (RR) with 95% confidence intervals (95% CIs) was used to calculate the data. Eleven studies were included in this study. Compared with phototherapy alone, combination treatment of tacrolimus and phototherapy significantly improved excellent response rate (RR = 1.40, 95% CI 1.16, 1.69; P < 0.001) and reduced the poor response rate (RR = 0.37, 95% CI 0.22, 0.61; P = 0.001). However, the good response rate (RR = 1.00, 95% CI 0.59, 1.69, P = 1.000) and moderate response rate (RR = 0.91, 95% CI 0.60, 1.38; P = 0.653) were not significantly different between the two treatments. Subgroup analysis suggested that combination treatment had a higher excellent response rate than phototherapy alone for lesions located in the face and proximal limbs. Both NB-UVB and EL, when added to tacrolimus, resulted in a significantly higher excellent response rate than they were used alone. Meta-regression analysis showed that age was a predictive factor that influenced the effect of combination treatment on an excellent response, in which children had a high excellent response to the treatment. Other demographic and clinical variables, including gender, disease duration, family history, and type of vitiligo, did not have any impact on the treatment effect. Combination treatment with tacrolimus and phototherapy was more effective than phototherapy monotherapy for patients with vitiligo, especially in the lesions located in the face and proximal limbs. More large-scale, well-performed trials are needed to verify our findings.