Understanding the Transcription Factor NFE2L1/NRF1 from the Perspective of Hallmarks of Cancer.

Cancer cells subvert multiple properties of normal cells, including escaping strict cell cycle regulation, gaining resistance to cell death, and remodeling the tumor microenvironment. The hallmarks of cancer have recently been updated and summarized. Nuclear factor erythroid 2-related factor 1 (NFE2L1, also named NRF1) belongs to the cap'n'collar (CNC) basic-region leucine zipper (bZIP) family. It acts as a transcription factor and is indispensable for maintaining both cellular homoeostasis and organ integrity during development and growth, as well as adaptive responses to pathophysiological stressors. In addition, NFE2L1 mediates the proteasome bounce-back effect in the clinical proteasome inhibitor therapy of neuroblastoma, multiple myeloma, and triple-negative breast cancer, which quickly induces proteasome inhibitor resistance. Recent studies have shown that NFE2L1 mediates cell proliferation and metabolic reprogramming in various cancer cell lines. We combined the framework provided by "hallmarks of cancer" with recent research on NFE2L1 to summarize the role and mechanism of NFE2L1 in cancer. These ongoing efforts aim to contribute to the development of potential novel cancer therapies that target the NFE2L1 pathway and its activity.

Synthesis of three cisplatin-conjugated asymmetric porphyrin photosensitizers for photodynamic therapy.

Photodynamic therapy provides a promising solution for treating various cancer types. In this study, three distinct asymmetric porphyrin-cisplatin complex photosensitizers (ZnPt-P1, ZnPt-P2, and ZnPt-P3) were synthesized, each having unique side chains. Through a set of experiments involving singlet oxygen detection and density functional theory, ZnPt-P1 was demonstrated to have excellent efficacy, exceeding that of ZnPt-P2 and ZnPt-P3. Notably, ZnPt-1 showed significant phototoxicity while maintaining low dark toxicity when tested on HepG2 cells. Additionally, further examination revealed that ZnPt-P1 had the capability to generate reactive oxygen species within cancer cells when exposed to light irradiation. Taken together, these results highlight the potential of ZnPt-P1 as a photosensitizer for use in photodynamic therapy. This study contributes to enhancing cancer treatment methodologies and provides insights for the future development of innovative drugs for photosensitization.

Liquid biopsy analysis of lipometabolic exosomes in pancreatic cancer.

Pancreatic cancer is characterized by its high malignancy, insidious onset and poor prognosis. Most patients with pancreatic cancer are usually diagnosed at advanced stage or with the distant metastasis due to the lack of an effective early screening method. Liquid biopsy technology is promising in studying the occurrence, progression, and early metastasis of pancreatic cancer. In particular, exosomes are pivotal biomarkers in lipid metabolism and liquid biopsy of blood exosomes is valuable for the evaluation of pancreatic cancer. Lipid metabolism is crucial for the formation and activity of exosomes in the extracellular environment. Exosomes and lipids have a complex relationship of mutual influence. Furthermore, spatial metabolomics can quantify the levels and spatial locations of individual metabolites in cancer tissue, cancer stroma, and para-cancerous tissue in pancreatic cancer. However, the relationship among exosomes, lipid metabolism, and pancreatic cancer is also worth considering. This study mainly updates the research progress of metabolomics in pancreatic cancer, their relationship with exosomes, an important part of liquid biopsy, and their lipometabolic roles in pancreatic cancer. We also discuss the mechanisms by which possible metabolites, especially lipid metabolites through exosome transport and other processes, contribute to the recurrence and metastasis of pancreatic cancer.

Lactate attenuates astrocytic inflammation by inhibiting ubiquitination and degradation of NDRG2 under oxygen-glucose deprivation conditions.

BACKGROUND: Brain lactate concentrations are enhanced in response to cerebral ischemia and promote the formation of reactive astrocytes, which are major components of the neuroinflammatory response and functional recovery, following cerebral ischemia. NDRG2 is upregulated during reactive astrocyte formation. However, its regulation and function are unclear. We studied the relationship between lactate and NDRG2 in astrocytes under conditions of ischemia or oxygen-glucose deprivation (OGD). METHODS: We examined astrocytic NDRG2 expression after middle cerebral artery occlusion (MCAO) using western blot and immunofluorescence staining. Under hypoxia conditions, we added exogenous L-lactate sodium (lactate) to cultured primary astrocytes to explore the effects of lactate on the ubiquitination modification of NDRG2. We profiled the transcriptomic features of NDRG2 silencing in astrocytes after 8 h of OGD conditions as well as exogenous lactate treatment by performing RNA-seq. Finally, we evaluated the molecular mechanisms of NDRG2 in regulating TNFα under OGD conditions using western blot and immunohistochemistry. RESULTS: Reactive astrocytes strongly expressed NDRG2 in a rat model of MCAO. We also showed that lactate stabilizes astrocytic NDRG2 by inhibiting its ubiquitination. NDRG2 inhibition in astrocytes increased inflammation and upregulated immune-associated genes and signaling pathways. NDRG2 knockdown induced TNFα expression and secretion via c-Jun phosphorylation. CONCLUSIONS: We revealed that under OGD conditions, lactate plays an important anti-inflammatory role and inhibits TNFα expression by stabilizing NDRG2, which is beneficial for neurological functional recovery. NDRG2 may be a new therapeutic target for cerebral ischemia.

Long non-coding RNAs as epigenetic mediator and predictor of glioma progression, invasiveness, and prognosis.

Gliomas are aggressive brain tumors with high mortality rate. Over the past several years, non-coding RNAs, specifically the long non-coding RNAs (lncRNAs), have emerged as biomarkers of considerable interest. Emerging data reveals distinct patterns of expressions of several lncRNAs in the glioma tissues, relative to their expression in normal brains. This has led to the speculation for putative exploitation of lncRNAs as diagnostic biomarkers as well as biomarkers for targeted therapy. With a focus on lncRNAs that have shown promise as epigenetic biomarkers in the proliferation, migration, invasion, angiogenesis and metastasis in various glioma models, we discuss several such lncRNAs. The data from cell line / animal model-based studies as well as analysis from human patient samples is presented for the most up-to-date information on the topic. Overall, the information provided herein makes a compelling case for further evaluation of lncRNAs in clinical settings.

The use of selective splenic vascular control in laparoscopic splenic vessels and spleen preservation distal pancreatectomy.

BACKGROUND: In the process of laparoscopic splenic vessels and spleen preservation distal pancreatectomy (LsvSPDP), because the splenic blood vessels have many small branches, how to safely separate the splenic blood vessels from the pancreas has always been the focus and difficulty of this operation. Many cases were switched to laparotomy, or the Warshaw method due to the inability to control bleeding during the separation of the splenic blood vessels. Therefore, we tried to use the selective splenic vascular control method when separating the splenic blood vessels to observe its effect on the conditions of the surgical patients during and after the operation. METHODS: We retrospectively collected 35 cases of LsvSPDP conducted in our center from September 2015 to December 2020, including 5 males and 30 females. Considering the influence of the surgical learning curve, the cases were divided into three groups. Finally, through statistics of its intraoperative and postoperative conditions, the effectiveness of selective splenic vascular control method can be judged. RESULTS: Patients in Group 2 and 3 showed significantly less blood loss (172.5 and 134.44 mL, respectively) compared to patients in Group 1 (541.43 mL; P=0.01). However, the amount of blood loss was not significantly different between Group 2 and 3. CONCLUSIONS: The amount of bleeding was significantly reduced by splenic blood vessel control technology. And it can improve the success rate of spleen preservation, preserve the success rate of splenic blood vessels, and reduce intraoperative bleeding.

The Role of Long Noncoding RNA AL161431.1 in the Development and Progression of Pancreatic Cancer.

Pancreatic cancer is known for its notorious fast progression and poor prognosis. Long noncoding RNA (lncRNA) AL161431.1 has been reported to be involved in the pathogenesis of different cancers. In this study, we explored the role of lncRNA AL161431.1 in the development and progression of pancreatic cancer by bioinformatic analysis, in vitro and in vivo experiments in pancreatic cancer BxPC-3 and SW1990 cells, as well as clinical samples. We found that lncRNA AL161431.1 was highly expressed in pancreatic cancer cells and tissues. Knock down of lncRNA AL161431.1 led to increased cancer cell death and cell cycle arrest. Xenograft growth of SW1990 cells with stable knockdown of lncRNA AL161431.1 in mice was significantly slower than that of SW1990 cells with scrambled control shRNA. Finally, we showed the involvement of lncRNA AL161431.1 in pancreatic cancer was related to its promotion of epithelial mesenchymal transition process.

A narrative review of a type of pancreatitis worthy of attention: acute pancreatitis associated with pancreatic tumors-current problems and future thinking.

OBJECTIVE: Our purpose is to explain the onset, diagnosis, and treatment of pancreatic tumor-associated pancreatitis (PTP), and inform clinicians about the management of PTP. It is hoped that clinicians can gain some experience and inspiration from this review, so that patients can obtain better treatment results. BACKGROUND: Acute pancreatitis (AP) is an inflammatory disease, and pancreatic tumors are one of the causes of pancreatitis. When pancreatic tumors and pancreatitis exist at the same time, and there is a "connection" between them, this type of pancreatitis is referred to as PTP. The manifestations of PTP can be as follows: (I) AP is the first symptom of pancreatic tumors; (II) pancreatitis is found in patients after pancreatic tumor diagnosis or during pancreatic tumor surgery. Because pancreatic tumors are not one of the most common causes of pancreatitis, PTP has not attracted the attention of researchers and clinicians, and there is no consistent and clear understanding of the diagnosis and treatment of PTP. METHODS: From the online database PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Web of Science (https://webofknowledge.com/), we use specific retrieval strategies to retrieve relevant articles, and we review and discuss them. CONCLUSIONS: What we need to realize is that PTP is different from ordinary AP. It has its own characteristics in terms of diagnosis and treatment, which requires the attention of clinicians. More importantly, future research should design the best diagnosis and treatment algorithms for PTP.

Narrative review of intraductal papillary mucinous neoplasms: pathogenesis, diagnosis, and treatment of a true precancerous lesion.

OBJECTIVE: Although considerable progress has been made in our understanding of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, there are still some problems to be solved. BACKGROUND: IPMN is one of the most important precancerous lesions of pancreatic cancer, but the relationship between IPMN and pancreatic cancer, and the specific mechanism of the development from IPMN to invasive carcinoma, remain to be explored in depth. With the development of imaging, the detection rate of IPMN has been greatly improved. However, the degree of malignancy of IPMN is difficult to assess, and its classification criteria and surgical treatment strategies are still controversial. Therefore, there is an urgent need for the best treatment plan for IPMN and research that can better predict IPMN recurrence and tumor malignancy. METHODS: From the online database Web of Science (https://webofknowledge.com/) and PubMed (https://pubmed.ncbi.nlm.nih.gov/), we use specific retrieval strategies to retrieve relevant articles based on the topics we discussed, and we review and discuss them. CONCLUSIONS: This paper discusses the related research and progress of IPMN in recent years to improve the understanding of the incidence, diagnosis, treatment, and prognosis of this disease. The follow-up and monitoring of IPMN is particularly important, but the specific strategy also remains controversial.

Primary gastric melanoma with pancreatic metastasis: a case report.

We report an extremely rare case of primary gastric melanoma with pancreatic metastasis. As far as we know, the concept of primary gastrointestinal melanoma is currently controversial, because there are very few reports of primary gastrointestinal melanoma. At the same time, isolated pancreatic metastases are also very rare. The patient was admitted to the hospital with a main complaint of decreased appetite, and then underwent gastroscopy and found a mass in the stomach. The mass was initially diagnosed as poorly differentiated adenocarcinoma following a gastroscopic biopsy. The patient underwent radical total gastrectomy, pancreatic body and tail resection, splenectomy, and Roux-en-Y esophagojejunostomy. After further immunohistochemical examination of the surgically removed tissue, malignant melanoma was diagnosed. The tumor cells were arranged in sheets or nests with infiltrating growth, the cell sizes were inconsistent, nucleoli were obvious, and melanin particles were seen in the cytoplasm of some cells. The tumor cells were positive for MITF and S-100. Detailed systemic and imaging examinations did not find any other primary lesions. The patient denied any melanoma and skin lesion history. We believe this is a manifestation of primary gastric melanoma. We report this rare case of gastric melanoma with the aim of increasing clinicians' awareness of non-cutaneous melanoma and its treatment methods.

Inflammatory myofibroblastic tumor in the pancreatic neck: a rare case report and literature review.

Inflammatory myofibroblastic tumor (IMT) is a rare disease of unknown etiology. It usually occurs in abdominal soft tissues and lung, and is extremely rare in the pancreas. IMT can occur in any part of a person at any age, however, it mostly affects children and young people. Its clinical manifestations are atypical, imaging examinations are not specific, and the differential diagnosis of pancreatic malignancies is difficult, making it easily misdiagnosed. Surgical resection is the preferred method of treatment for IMT. In this case report, we report a rare case of IMT in the neck of the pancreas and reviewed the relevant literature. In our case, the patient was a 57-year-old woman with an IMT in the neck of the pancreas. Abdominal pain was the only clinical symptom, and imaging features were not specific. She underwent surgery to remove the pancreatic mass, and the final diagnosis of IMT was based on histopathology and immunohistochemistry. After 6 months of regular follow-up, the patient had no complications or further incidents. The purpose is to emphasize the difficulty of the preoperative diagnosis of pancreatic IMT and the difficulty of distinguishing it from pancreatic malignancies. It is hoped that clinicians can gain a deeper understanding of pancreatic IMT through this case report.

Long non-coding RNA ELFN1-AS1 in the pathogenesis of pancreatic cancer.

BACKGROUND: Long non-coding ribonucleic acid (lncRNA) ELFN1 antisense RNA 1 (ELFN1-AS1) is involved in the pathogenesis of many different cancers. But the current research on the relationship between lncRNA ELFN1-AS1 and pancreatic cancer is still blank. METHODS: We investigated the role of lncRNA ELFN1-AS1 in the pathogenesis of pancreatic cancer using bioinformatics, in vitro and in vivo experiments in pancreatic cancer cell lines, and surgically removed clinical samples. RESULTS: Through bio-information analysis and in vitro and in vivo experiments, we found that LncRNA ELFN1-AS1 was highly enriched in pancreatic cancer data sets and highly expressed in pancreatic cancer cell lines and tissues. The knocking down of lncRNA ELFN1-AS1 significantly increased cancer cell death and growth arrest. Xenografts in nude mice showed that the growth of SW1990 cells in the mice group with a stable knock down of lncRNA ELFN1-AS1 was significantly slower than that in the control group. CONCLUSIONS: The experimental results show that the expression of LncRNA ELFN1-AS1 is related to the growth and invasion ability of pancreatic cancer cells. By further studying the function of LncRNA ELFN1-AS1 in pancreatic cancer, LncRNA ELFN1-AS1 was found to be involved in the epithelial-mesenchymal transition process in pancreatic cancer.

Circ-0005105 activates COL11A1 by targeting miR-20a-3p to promote pancreatic ductal adenocarcinoma progression.

Growing evidence indicates that circular RNAs (circRNAs) are closely involved in tumorigenesis, but the association between circRNAs and pancreatic ductal adenocarcinoma (PDAC) is far from clear. Here, we focused on the functional investigation of circ-0005105, a newly identified circRNA, in PDAC progression. In the present study, we assessed circ-0005105 expression in PDAC tissues and cell lines with quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The biological functions of circ-0005105 in cellular proliferation and invasion were identified through gain- and loss-of-function experiments in vitro and in vivo. The interaction between circ-0005105 and the microRNA (miR)-20a-3p-COL11A1 (collagen type XI alpha 1) axis was examined using luciferase reporter and RNA immunoprecipitation assays. We found that circ-0005105 expression was upregulated in both PDAC tissues and cell lines. Higher circ-0005105 expression correlated positively with the malignant clinical phenotype and poor prognosis of patients with PDAC. Gain- and loss-of-function analysis showed that circ-0005105 facilitated both in vitro and in vivo cellular proliferation and invasion. Mechanistically, circ-000510 served as a competing endogenous RNA (ceRNA) of miR-20a-3p and indirectly modulated COL11A1 expression, leading to activation of epithelial-mesenchymal transition (EMT). Rescue experiments suggested that the oncogenic activity of circ-0005105 was dependent on the modulation of the miR-20a-3p-COL11A1 axis. More importantly, COL11A1 overexpression was significantly associated with poor prognosis in PDAC, and silencing COL11A1 reduced PDAC cell tumorigenicity and metastasis. Taken together, our findings confirm for the first time that circ-0005105 has critical functions by regulating the miR-20a-3p-COL11A1 axis. In the clinic, circ-0005105 can act as a potential prognostic marker and therapeutic target in PDAC.

Development of L-carnosine functionalized iron oxide nanoparticles loaded with dexamethasone for simultaneous therapeutic potential of blood brain barrier crossing and ischemic stroke treatment.

The development of suitable drug delivery carriers is significant in biomedical applications to improve the therapeutic efficiency. Recent progress in nanotechnological fields, paved the way for the formulation of variety of drug carriers. The brain disorders such as ischemic stroke, brain cancer, and CNS disorders were poorly treated due to the presence of blood brain barrier that hinders the passage of drugs to the brain. Hence, the formulated drugs should have the ability to cross the blood-brain barrier (BBB) for ischemic stroke treatment. In the present work, we have synthesized PLGA functionalized magnetic Fe3O4 nanoparticle (MNP) with L-carnosine peptide (LMNP) composite loaded with dexamethasone (dm@LMNP) and demonstrated as efficient drug delivery platform for simultaneous BBB crossing and treatment of ischemic stroke. The surface morphology, particles size and zeta potential of the prepared material was studied from SEM, PSD, PDI and TEM analyses. The drug loading of dexamethasone in LMNP (dm@LMNP) vesicles was found to be 95.6 ± 0.2%. The in vitro drug release kinetics displayed that prepared composited LMNP material provides controlled and sustainable releasing efficiency at pH 7.4 and 5.8 when compared to the PLGA NPs and free dexamethasone drug molecules. The cytotoxicity and the biocompatibility test results were found to be satisfactory. The L-carnosine loaded nano-formulation has been greatly leads to effective BBB crossing to access the brain tissues. These results showed that the Fe3O4 nanoparticles/PLGA polymer can be used as an effective drug carrier for the treatment of stroke and simultaneous blood brain barrier crossing.

Developing a toolbox for identifying when to engage senior surgeons in emergency general surgery: A multicenter cohort study.

BACKGROUND: Having a senior surgeon present for high-risk patients is an important safety measure in emergency surgery, but 24-h consultant cover is not efficient. We aimed to develop a user-friendly toolbox (risk identification, outcome prediction and patient stratification) to support when to involve a senior surgeon. MATERIALS AND METHODS: We included 11,901 general surgery patients (10.0% emergencies) in a multicenter prospective cohort in China (2015-2016). Patient information and surgeons' seniority were compared between emergency and elective surgery with the same procedure codes. Risk indicators common in these two surgical timings and specific to emergency surgery were identified, and their clinical importance was evaluated by a working group of 48 experienced surgeons. Predictive models for mortality and morbidity were built using logistic regression models. Stratification rules were created to balance patients' risk and surgeons' caseload with an Acute Call Team (ACT) model. RESULTS: Emergency patients had significantly higher risks of mortality (3.6% vs 0.6%) and morbidity (7.8% vs 4.3%) than elective patients, but disproportionally fewer senior surgeons (59.9% vs 91.4%) were present. Using three risk indicators (American Society of Anesthesiologists score, age, blood urea nitrogen), C-statistic (95% CI) for prediction of emergency mortality was high [0.90 (0.84-0.96)]. It was less complex but equally accurate as two existing and validated models (0.86 [0.79-0.93] and 0.86 [0.77-0.95]). Using five indicators, C-statistic (95% CI) was moderate for prediction of overall morbidity [0.77 (0.72-0.83)], but high for severe morbidity [0.92 (0.88-0.97)]. Based on stratification rules of the ACT model, patient mortality and morbidity were 0.5% and 5.3% in the low-risk stratum (composing 64.6% of emergency caseload), and 15.9% and 29.0% in the very high-risk stratum (6.9% of caseload). CONCLUSION: These findings show the practical feasibility of using a risk assessment tool to direct senior surgeons' involvement in emergency general surgery.

Intracranial Dural Arteriovenous Fistulas With Brainstem Engorgement: An Under-Recognized Entity in Diagnosis and Treatment.

Background: In rare circumstances, patients with intracranial (dural arteriovenous fistulas) DAVFs could be complicated with brainstem engorgement, which might lead to delayed or false diagnosis and subsequent improper management. Methods: On July 2th, 2019, a systematic search was conducted in the PubMed database for patients with intracranial DAVFs complicated with brainstem engorgement. Results: Sixty-eight articles reporting of 86 patients were included for final analysis. The patients were aged from 20 to 76 years (57.10 ± 12.90, n = 82). The female to male ratio was 0.68 (35:51). Thirty-three (40.2%, 33/82) patients were initially misdiagnosed as other diseases. The specific location distributions were cranio-cervical junction, cavernous sinus, superior petrosal sinus, transverse and/or sigmoid sinus, tentorium, and other sites in 27 (32.5%), 11 (13.2%), 9 (10.8%), 10 (12.0%), 21 (25.3%), and 5 (6.0%) patients, respectively. The Cognard classification of DAVFs were II, III, IV, and V in 9 (10.7%, 9/84), 1 (1.2%, 1/84), 1 (1.2%, 1/84), and 73 (86.9%, 73/84) patients. Eighteen (22%, 18/82) patients were demonstrated to have stenosis or occlusion of the draining system distal to the fistula points. The mean follow-up period was 7.86 (n = 74, range 0-60 months) months. Fifty-four (70.1%, 54/77) patients experienced a good recovery according to the mRS score. Conclusions: Intracranial DAVFs complicated with brainstem engorgement are rare entities. Initial misdiagnosis and delayed definite diagnosis are common in the past three decades. The treatment outcome is still unsatisfactory at present. Early awareness of this rare entity and efficiently utilizing the up to date investigations are of utmost importance.

Ileocecal intussusception caused by two different tumors - which is the culprit lesion? A case report.

BACKGROUND: Ileocecal intussusception caused by two different tumors is rare, according to a literature review. We describe a case of a male patient with a cauliflower-like mass in the middle of the transverse colon observed by colonoscopy before surgery. It was considered to be intussusception caused by colon cancer. However, a substantial lipomatous mass was seen in the distal end of the intussusception by computed tomography before surgery, which posed a challenge in the preoperative diagnosis. CASE SUMMARY: We report a 72-year-old male patient with intussusception. The patient underwent right hemicolectomy and cholecystectomy in our hospital on April 29, 2019. During operation, the ileum was inserted into the ascending colon by about 15 cm, and a tumor with a diameter of approximately 3.0 cm was observed in the distal part of the intestine. An atypical liposarcoma/highly differentiated liposarcoma in the adipose tissue was suspected in the postoperative pathology, and a lipoma was diagnosed after MDM2 gene testing. A 4.0 cm × 5.0 cm polypoid mass was seen immediately adjacent to the mass, and the postoperative pathology report suggested a high-level tubular adenoma. The patient was eventually cured and discharged with an uneventful follow-up. CONCLUSION: Intussusception caused by two different types of masses is extremely rare. At present, surgery is the best treatment once intussusception is diagnosed.

Endovascular treatment of the cavernous sinus dural arteriovenous fistula: current status and considerations.

A cavernous sinus dural arteriovenous fistula (CS-DAVF) is an abnormal arteriovenous communication involving the dura mater within or near the CS wall. The dural arteries from the internal carotid artery and external carotid artery supply the CS-DAVF, and the superior ophthalmic vein (SOV) and inferior petrous sinus (IPS) are frequent venous drainers. In CS-DAVF cases, high-risk lesions require treatment. Endovascular treatment (EVT) has been the first-line option for CS-DAVFs. To our knowledge, a review of the EVT of CS-DAVFs is lacking. Therefore, in this paper, we review the available literature on this issue. In addition, some illustrative cases are also provided to more concisely expound the EVT of CS-DAVFs. According to the recent literature, transvenous embolization via the IPS is considered the most effective method for EVT of CS-DAVFs. In addition, the transorbital approach is another reasonable choice. Other venous approaches can also be tried. Because of the low cure rate, transarterial embolization for CS-DAVFs is limited to only highly selected patients. In the EVT of CS-DAVFs, various agents have been used, including coil, Onyx, and n-butyl cyanoacrylate, with coil being the preferred one. In addition, when EVT cannot obliterate the CS-DAVF, stereotactic radiotherapy may be considered. In general, despite various complications, EVT is a feasible and effective method to manage CS-DAVFs by way of various access routes and can yield a good prognosis.

Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway.

BACKGROUND: Mesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats. METHODS: We established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis- and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays. RESULTS: The dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis. CONCLUSION: BMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury.

Huge primary dedifferentiated pancreatic liposarcoma mimicking carcinosarcoma in a young female: A case report.

BACKGROUND: Pancreatic liposarcoma is a rare tumor. According to a literature review, the patient described in this study is the seventh case of pancreatic liposarcoma reported in the English literature and the third case of dedifferentiated liposarcoma. Furthermore, this case had the largest primary tumor volume, and a primary pancreatic liposarcoma was diagnosed based on sufficient evidence. CASE SUMMARY: We here report a rare case of a 28-year-old female with a huge dedifferentiated liposarcoma in the pancreatic tail. In June 2015, the patient underwent distal pancreatectomy with splenectomy. During the operation, a huge liposarcoma of approximately 28.0 cm × 19.0 cm × 8.0 cm was found, which had a yellow and white fish-like incisal surface. Based on both pathology and MDM2 gene amplification, the tumor was diagnosed as a dedifferentiated liposarcoma. The patient was treated with surgery but declined postoperative chemotherapy. She was well at the 26-mo follow-up, and no relapse was observed. CONCLUSION: Pancreatic liposarcoma has a low incidence. Chemotherapy should be included in the treatment regimens. Complete resection is the only effective treatment.