Carnosine regulation of intracellular pH homeostasis promotes lysosome-dependent tumor immunoevasion.

Tumor cells and surrounding immune cells undergo metabolic reprogramming, leading to an acidic tumor microenvironment. However, it is unclear how tumor cells adapt to this acidic stress during tumor progression. Here we show that carnosine, a mobile buffering metabolite that accumulates under hypoxia in tumor cells, regulates intracellular pH homeostasis and drives lysosome-dependent tumor immune evasion. A previously unrecognized isoform of carnosine synthase, CARNS2, promotes carnosine synthesis under hypoxia. Carnosine maintains intracellular pH (pHi) homeostasis by functioning as a mobile proton carrier to accelerate cytosolic H+ mobility and release, which in turn controls lysosomal subcellular distribution, acidification and activity. Furthermore, by maintaining lysosomal activity, carnosine facilitates nuclear transcription factor X-box binding 1 (NFX1) degradation, triggering galectin-9 and T-cell-mediated immune escape and tumorigenesis. These findings indicate an unconventional mechanism for pHi regulation in cancer cells and demonstrate how lysosome contributes to immune evasion, thus providing a basis for development of combined therapeutic strategies against hepatocellular carcinoma that exploit disrupted pHi homeostasis with immune checkpoint blockade.

Non-canonical phosphoglycerate dehydrogenase activity promotes liver cancer growth via mitochondrial translation and respiratory metabolism.

Phosphoglycerate dehydrogenase (PHGDH) is a key serine biosynthesis enzyme whose aberrant expression promotes various types of tumors. Recently, PHGDH has been found to have some non-canonical functions beyond serine biosynthesis, but its specific mechanisms in tumorigenesis remain unclear. Here, we show that PHGDH localizes to the inner mitochondrial membrane and promotes the translation of mitochondrial DNA (mtDNA)-encoded proteins in liver cancer cells. Mechanistically, we demonstrate that mitochondrial PHGDH directly interacts with adenine nucleotide translocase 2 (ANT2) and then recruits mitochondrial elongation factor G2 (mtEFG2) to promote mitochondrial ribosome recycling efficiency, thereby promoting mtDNA-encoded protein expression and subsequent mitochondrial respiration. Moreover, we show that treatment with a mitochondrial translation inhibitor or depletion of mtEFG2 diminishes PHGDH-mediated tumor growth. Collectively, our findings uncover a previously unappreciated function of PHGDH in tumorigenesis acting via promotion of mitochondrial translation and bioenergetics.

Associated factors of periodontitis and predicted study among young man in China: a population-based cross-sectional study.

BACKGROUND: Periodontitis represents the foremost oral condition in young men, strongly correlated with socioeconomic elements and oral health behaviors. This research aimed to assess the prevalence of periodontitis and associated associations with socio-demographics and oral health practices for subsequent Hazard Ratio (HR) estimation. METHODS: A total of 46,476 young men were recruited to the study between August 2022 and October 2023. A questionnaire on socio-demographic factors and oral health-related behaviors related to periodontitis was completed. The standard procedure was used for oral examination. Logistic regression and hazard ratios were used to estimate the influencing factors, whereas the nomogram was used to predict the risk of periodontitis in young men. RESULTS: A total of 46,476 young men were surveyed and completed the questionnaire. The overall prevalence of periodontitis among young men was 1.74%. Out of these, 1.7% had mild periodontitis and 0.6% had moderate periodontitis. Age and dental calculus were important factors in the periodontal health of young men. This nomogram, which includes 7 easily obtainable clinical characteristics routinely collected during periodontitis risk assessment, provides clinicians with a user-friendly tool to assess the risk of periodontal disease in young men. CONCLUSIONS: Regular dental prophylaxis is crucial for young men to maintain their gingival health and prevent the onset of periodontitis. Dental calculus plays a prominent role in this matter, as it serves as a significant contributing factor.

MYC promotes cancer progression by modulating m6 A modifications to suppress target gene translation.

The MYC oncoprotein activates and represses gene expression in a transcription-dependent or transcription-independent manner. Modification of mRNA emerges as a key gene expression regulatory nexus. We sought to determine whether MYC alters mRNA modifications and report here that MYC promotes cancer progression by down-regulating N6-methyladenosine (m6 A) preferentially in transcripts of a subset of MYC-repressed genes (MRGs). We find that MYC activates the expression of ALKBH5 and reduces m6 A levels in the mRNA of the selected MRGs SPI1 and PHF12. We also show that MYC-regulated m6 A controls the translation of MRG mRNA via the specific m6 A reader YTHDF3. Finally, we find that inhibition of ALKBH5, or overexpression of SPI1 or PHF12, effectively suppresses the growth of MYC-deregulated B-cell lymphomas, both in vitro and in vivo. Our findings uncover a novel mechanism by which MYC suppresses gene expression by altering m6 A modifications in selected MRG transcripts promotes cancer progression.

Connexin43 reduces LPS-induced inflammation in hDPCs through TLR4-NF-κB pathway via hemichannels.

OBJECTIVES: Connexin43 (Cx43) is involved in the inflammation of many tissue types. Dental caries is infectious disease resulting from mineralized tissue dissolution by a specific bacterial population, causing pulp inflammation. However, Cx43's role in dental pulp remains unclear. Here, we investigated the function of Cx43 during pulp inflammation. MATERIALS AND METHODS: We constructed a dentin injury model in Sprague-Dawley rats to investigate changes in Cx43 expression during pulp inflammation. Cx43 was inhibited in human dental pulp cells (hDPCs) that had been stimulated with lipopolysaccharide (LPS) to investigate the effect of Cx43 on inflammatory response. Promotion of TLR4-NF-κB pathway activity and special Cx43 channel inhibitors were used to clarify the function of Cx43 in hDPCs. RESULTS: Dentin injury led to low-level inflammation in dental pulp. Following dentin injury, Cx43 expression initially decreased before gradually recovering to normal levels. Cx43 inhibition reduced LPS-induced expression of inflammatory cytokines and NF-κB pathway activity. Promotion of NF-κB pathway activity counteracted the effect of Cx43 in hDPCs. Furthermore, inhibition of Cx43 hemichannels reduced LPS-induced inflammatory cytokine expression. CONCLUSIONS: Cx43 is involved in inflammation of dental pulp, while its inhibition reduced LPS-induced inflammation in hDPCs through NF-κB pathway via blockage of hemichannels.

Fully endoscopic microvascular decompression for trigeminal neuralgia: technical note and early outcomes.

Microscopic microvascular decompression (MVD) has been considered a curative and reliable method for treating classical trigeminal neuralgia (TN) for decades. Endoscopy can provide bright illumination and a panoramic view, which enhances the visualization of the posterior fossa. In view of the above advantages of endoscopy, it gradually became an option for MVD for treating TN. This study was performed to evaluate the advantages of fully endoscopic MVD for treating TN and is presented with a description of our operative technique. From January 2020 to January 2022, 95 classical TN patients underwent fully endoscopic MVD performed by the same surgeon and assistant in our department. The assistant held the endoscope, and the surgeon operated. Brain stem auditory evoked potentials (BEMPs) were routinely monitored. For every patient, the neurovascular conflict was identified, and complete decompression was achieved. The Barrow Neurological Institute (BNI) pain intensity score was used to evaluate the degree of facial pain. The intraoperative findings, postoperative outcomes, and complications were analyzed. Immediately after the operation, 93 patients (97.9%) achieved complete pain relief (BNI score of I). Two patients (2.1%) still had some pain, but it could be adequately controlled with medicine (BNI score of III). During the 12-36 months of follow-up, recurrence was found in 3 patients (3.2%), including one patient (1.1%) with a BNI score of II and 2 patients (2.1%) with a BNI score of III. Complications were found in 5 patients (5.3%), including facial numbness in 3 patients (3.2%), vertigo in one patient (1.1%), and headache in one patient (1.1%). There were no cases of mortality, stroke, hearing impairment, facial paralysis, or other complications. Fully endoscopic MVD is a safe and effective method for treating TN. It provides bright illumination and a panoramic view for surgeons to better observe neurovascular conflicts in deep areas of the cerebellopontine angle (CPA).

PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation.

Tumor metabolic reprogramming and epigenetic modification work together to promote tumorigenesis and development. Protein lysine acetylation, which affects a variety of biological functions of proteins, plays an important role under physiological and pathological conditions. Here, through immunoprecipitation and mass spectrum data, we show that phosphoglycerate mutase 5 (PGAM5) deacetylation enhances malic enzyme 1 (ME1) metabolic enzyme activity to promote lipid synthesis and proliferation of liver cancer cells. Mechanistically, we demonstrate that the deacetylase SIRT2 mediates PGAM5 deacetylation to activate ME1 activity, leading to ME1 dephosphorylation, subsequent lipid accumulation and the proliferation of liver cancer cells. Taken together, our study establishes an important role for the SIRT2-PGAM5-ME1 axis in the proliferation of liver cancer cells, suggesting a potential innovative cancer therapy.

Ginkgetin Promotes M2 Polarization of Microglia and Exert Neuroprotection in Ischemic Stroke via Modulation of PPARγ Pathway.

Neuroinflammation plays an important role in the pathophysiological process of acute cerebral infarction, which may aggravate brain injury and hinder neuro-repair. Microglia are innate immune cells in the brain. Ginkgetin has anti-inflammatory and neuroprotective effects, but the mechanism remains unclear. This study aims to explore the regulatory effects of ginkgetin on microglia polarization in brain ischemia. Oxygen glucose deprivation (OGD) cellular model and middle cerebral artery occlusion (MCAO) animal model was used in this study. We first observed the dynamic process of microglia polarization in ischemic stroke, and then investigated the effect of ginkgetin treatment on microglia polarization. Finally, we studied the role of PPARγ signaling pathway and the blocking effect of PPARγ antagonist GW9662 in this process. OGD and cerebral ischemia polarized microglia mainly to M1 type. However, ginkgetin treatment converted microglia from M1 type to M2 type, inhibited neuroinflammation, and exerted neuronal protective effects. PPARγ signaling pathway was activated during this process. The above effects could be blocked by GW9662. Ginkgetin can promote M2 polarization of microglia through PPARγ signaling pathway, thereby inhibiting neuroinflammation and promoting recovery of neurological functions in ischemic stroke.

Microvascular decompression for pediatric onset trigeminal neuralgia: patterns and variation.

OBJECTIVES: Pediatric trigeminal neuralgia has been rarely reported in the literature, which were only 28 cases. Although microvascular decompression (MVD) has been widely accepted as effective therapy for trigeminal neuralgia, the etiology and surgical treatment of pediatric ones are seldom addressed. We report our experience with MVD for pediatric trigeminal neuralgia patients with emphasis on the vascular conflict patterns and surgical skills. METHODS: This retrospective report included 11 pediatric TN patients, who underwent MVD and were followed for 3-86 months. The data were retrospectively analyzed with emphasis on the clinical features. RESULTS: This series included 4 boys and 7 girls with average age of 13 ± 3.4 years old, their onset age were from 7 to 18 years old. The singular vein and combined artery/vein conflictions account for 7/11. 9 (81.8%) patients achieved immediate excellent outcomes. One recurrence was observed after 5 months and refused the second surgery. CONCLUSIONS: The etiology of pediatric onset trigeminal neuralgia is still vascular conflict, whose patterns are different from adults, of which combined artery/vein and singular venous compression patterns have a much more higher proportion. Because of the smaller operative space and fragile-thin venous wall with adhesion to other structures, it is much more difficult to decompress the trigeminal nerve among pediatric patients. Sufficient arachnoid release, full exploration, and decompression along the trigeminal nerve were necessary, which will increase the excellent rate among pediatric patients.

New Technology: Compound Abnormal Muscle Response During Microvascular Decompression for Hemifacial Spasm.

OBJECTIVE: To discuss effect of intraoperative compound abnormal muscle response (AMR) in patients undergoing microvascular decompression (MVD) for hemifacial spasm (HFS). METHODS: Eighty-six HFS patients were underwent single or compound AMR monitoring during MVD. Single AMR recording was from the frontal muscle by stimulation of the marginal mandibular branch. Compound AMR recordings were obtained from the orbicularis oris and mentalis muscles by electrical stimulation of the temporal branch of the facial nerve, and from the frontal and orbicularis oculi muscles by stimulation of the marginal mandibular branch. Clinical outcome was compared with compound AMR results at the completion of MVD. RESULTS: Forty-two of 45 patients' AMR were recorded by compound AMR monitoring and 34 of 41 patients' AMR were recorded by single AMR monitoring during MVD. Hemifacial spasm resolved completely in 41 patients whose compound AMR was recorded and in 26 patients whose single AMR was recorded. Compound AMR gained a sensitivity of 96.3% and a specificity of 97.2%. Correspondingly, single AMR gained a sensitivity of 97.1% and a specificity of 86.3%. CONCLUSIONS: Our results suggest that compound AMR is more suitable than single AMR in MVD for HFS.

Circumventing Drug Resistance Pathways with a Nanoparticle-Based Photodynamic Method.

Drug resistance remains the dominant impediment for cancer therapy, not only because compensatory drug resistance pathways are always activated, but also because of the cross-resistance of cancer cells to unrelated therapeutics. Herein, chemodrug-sensitive cancer cells, intrinsic drug-resistant cells, and acquired resistant cells were employed to uncover their biological response to a nanoparticle-based photodynamic method in tumoral, cellular, and molecular levels. We observed that nanoparticle-based photodynamic process with high therapeutic efficiency, intracellular delivery, and tumor penetration effect resulted in the indiscriminate and significant therapeutic outcome, in contrast to the diversiform effect of first-line chemo-drug, Temozolomide (TMZ). By real-time quantitative PCR array technique, we revealed that signals in classical resistance pathways were unaffected or downregulated, and photodynamic effect initiates cell apoptosis via downstream genes. The discovery that nanoparticulate photodynamic therapy bypasses the signals in multiple resistant pathways may imply an alternative route for combating drug resistance of cancer.

How to obtain industrial waste data at the county scale: Two downscaling models and their application in Dongguan, China.

The availability of environmental emission data is critical in evaluation of countries' ecological security and the implementation of environmental management. However, access to environmental emission data at the county level is not provided by statistical publications and bulletins. Therefore, in this paper, we develop two novel data downscaling models, an environmental Kuznets curve downscaling model (EKCDM) and a scale model (SM), to obtain county-level environmental emission data. The EKCDM relies on the EKC hypothesis and the assumption that the same model applies across scales, whereas the SM depends on the assumption that the share of a region's environmental pollution is equivalent to its share of economic output. Subsequently, environmental emission data above the county scale can be obtained through model transformation and simple calculations. By verifying and analyzing the official data with the one obtained through downscaling at municipal level and above, we verify the feasibility of the models, after which we apply the models to extrapolate information on the industrial waste of the counties of Dongguan city in Guangdong Province, China. We find that the EKCDM should be given priority in most cases, especially for the quadratic parameter model, and that the SM can be adopted when per capita gross domestic product differs greatly between adjacent levels of administrative units. In general, scholars can synthesize the characteristics of these two models, and obtain more accurate data by supplementing and verifying one with the other. Compared with other downscaling methods, our methods require far less data and the concepts are easily understood, which makes them more feasible and increases applicability. This study provides scholars with powerful tools to explore the relationship between industrial pollution and economic development in depth by obtaining industrial waste data at the county scale, thereby supporting scientific research and policy design.

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway.

Many factors are involved in the process of nerve regeneration. Understanding the mechanisms regarding how these factors promote an efficient remyelination is crucial to deciphering the molecular and cellular processes required to promote nerve repair. Schwann cells (SCs) play a central role in the process of peripheral nerve repair/regeneration. Using a model of facial nerve crush injury and repair, we identified Annexin A1 (ANXA1) as the extracellular trigger of SC proliferation and migration. ANXA1 activated formyl peptide receptor 2 (FPR2) receptors and the downstream adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling cascade, leading to SC proliferation and migration in vitro. SCs lacking FPR2 or AMPK displayed a defect in proliferation and migration. After facial nerve injury (FNI), ANXA1 promoted the proliferation of SCs and nerve regeneration in vivo. Collectively, these data identified the ANXA1/FPR2/AMPK axis as an important pathway in SC proliferation and migration. ANXA1-induced remyelination and SC proliferation promotes FNI regeneration.

A successful treatment of hemifacial spasm due to anterior inferior cerebellar artery aneurysm in adolescent: a case report and literature review.

OBJECTIVE: Hemifacial spasm (HFS) is usually caused by compression of the facial nerve at the root exit zone (REZ), and is extremely rare in adolescents and even rarer in aneurysm compression. CASE REPORT: We describe symptomatic hemifacial spasm caused by a saccular aneurysm of the anterior inferior cerebellar artery (AICA) that was treated by clipping. A 17-year-old adolescent developed left hemifacial spasm that had gradually worsened over a period of 1 year before admission to our department. During the course of MVD (microvascular decompression), saccular aneurysm of AICA was accidentally found to compress the facial nerve. The cause of the facial spasm was considered to be compression of the left facial nerve by the aneurysm. Clipping the aneurysm was performed. The hemifacial spasm disappeared immediately. CONCLUSION: Our report indicates that HFS caused by saccular aneurysm of AICA can be treated by clipping, and that aneurysms should be considered in the treatment of adolescent HFS, especially those difficult to identify on imaging examination.

Epineurectomy of Facial Nerve Trunk for Refractory Oral-Ocular and Oculo-Oral Synkinesis Following Bell Palsy.

BACKGROUND: Synkinesis is a common sequelae after incomplete recovery from Bell palsy. Current first-line treatments include botulinum toxin injection and physical therapy. However, patients unresponsive to these treatments may require further surgery. Various surgical treatments have been reported, but no consensus has been reached for the optimal surgery. In a guinea pig model of synkinesis, the facial nerve trunk (FNT) was observed using a scanning electron microscope. Based on the results of scanning electron microscope and clinical ultrasonography, the authors chose FNT as the therapeutic target. METHODS: The authors performed epineurectomy of FNT for 11 patients with refractory oral-ocular and oculo-oral synkinesis under abnormal muscle response and facial electromyography monitoring. The postoperative assessments at 1 year were conducted using Sunnybrook Facial Grading System and Facial Disability Index scale. Furthermore, the epineurium excised during the operation was collected as the specimen and submitted for histopathological examination; the cadaveric FNT served as the control group. RESULTS: The follow-up results showed significant relief from synkinesis (4.91 ±â€Š0.37 versus 10.18 ±â€Š0.64, P < 0.01), improvement of physical (84.55 ±â€Š1.96 versus 73.18 ±â€Š3.65, P < 0.01) and social functions (77.09 ±â€Š3.24 versus 61.82 ±â€Š6.28, P < 0.01), with no worsening of facial paralysis in the patients. The histopathological examination revealed many nerve fibers in the epineurium, suggesting that FNT was the area of aberrant axon regeneration. CONCLUSIONS: Epineurectomy of FNT is a safe and effective surgical remedy. It can be considered as a surgical option for patients with refractory oral-ocular and oculo-oral synkinesis following Bell palsy.

Overexpression of Foxc1 regenerates crushed rat facial nerves by promoting Schwann cells migration via the Wnt/ß-catenin signaling pathway.

Facial paralysis can result in severe implications for patients. A good prognosis depends on the degree of nerve regeneration. Schwann cells (SCs) play an important role in facial nerve development and regeneration through migration. Forkhead box C1 (Foxc1), a member of the forkhead transcription factor family, is implicated in cell migration. However, the role of Foxc1 in the progression after facial nerve crush remains unknown. Our aim was to evaluate the effect of Foxc1 overexpression on SC migration and recovery of facial nerves after crush injury. The rat facial nerve crush injury model was established through the use of unilateral surgery. The results showed that the expression of Foxc1 was increased in the surgery group compared to that of the control group. SCs were isolated from the sciatic nerves and cultured. Foxc1, delivered by an adeno-associated virus in vivo, or adenovirus in vitro, both induced overexpression of Foxc1, and increased the expression of CXCL12 and ß-catenin. After the transfection of Foxc1, the migration of SC was increased both in vitro and in vivo, was reduced by the inhibition of CXCL12 or ß-catenin. The facial nerve function and the nerve axon remyelination of the rats transfected with Foxc1 were significantly improved after nerve crush injury. Overall, the results demonstrated that overexpression of Foxc1 promoted SC migration by regulating CXCL12 via the Wnt/ß-catenin pathway, thus contributing to improved facial nerve function after crush injury.

Metagenomic next-generation sequencing of viruses, bacteria, and fungi in the epineurium of the facial nerve with Bell's palsy patients.

Bell's palsy (BP) represents a major cause leading to facial paralysis in the world. The etiology of BP is still unknown, and virology is the prevailing theory. The purpose of this study is to explore the pathogenic microorganisms that may be related to BP, and it is of great significance to study the pathogenesis and treatment of BP. Metagenomic next-generation sequencing (mNGS) detection was performed in the epineurium of the facial nerve of 30 BP patients who underwent facial nerve epineurium decompression. A total of 84 pathogenic microorganisms were detected in 30 clinical samples, including 4 viruses, 10 fungi, and 70 bacteria. The species with the highest detection frequency in virus was human betaherpesvirus 7 (HHV-7). The species with the highest detection frequency in Fungi was Malassezia restricta. The species with the highest detection frequency in Bacteria was Pseudomonas aeruginosa. In this study, mNGS method was firstly used to detect the pathogenic microorganisms in the epineurium of the facial nerve with BP patients. We have for the first time identified HHV-7 and aspergillus in the epineurium of the facial nerve of BP patients. These results suggest that these two pathogenic microorganisms should be considered in the pathogenesis of BP.

DGUOK-AS1 promotes cell proliferation in cervical cancer via acting as a ceRNA of miR-653-5p.

Cervical cancer (CC) holds the second highest incidence and is the fourth dominating cause of cancer-induced death in women. It has been widely accepted that long noncoding RNAs (lncRNAs) are implicated in pathological and physiological activities of CC. However, the research of lncRNAs is still in the initial stage. The biological function of lncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) in human cancers has not been reported yet. We found that DGUOK-AS1 was aberrantly upregulated in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tissues through TCGA database. Real-time quantitative polymerase chain reaction (RT-qPCR) also verified the high expression of DGUOK-AS1 in CC cell lines. Loss-of-function assays indicated that DGUOK-AS1 silence repressed CC cell growth. In addition, dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments validated the binding relation between miR-653-5p and DGUOK-AS1 or EMSY. Results of the rescue assays elucidated that EMSY overexpression or miR-653-5p downregulation reversed the suppressive function of DGUOK-AS1 knockdown on cell growth and DNA repair in CC. To sum up, this research highlighted that DGUOK-AS1 could promote CC cell proliferation via serving as a ceRNA of miR-653-5p to release EMSY, which might inspire us to discover novel strategies for CC treatment. SIGNIFICANCE OF THE STUDY: DGUOK-AS1 knockdown hinders proliferation of CC cells. DGUOK-AS1 sequesters miR-653-5p to elevate EMSY in CC. EMSY is required for DGUOK-AS1 to induce cell proliferation and repress DNA damage in CC.

Exosomal LncRNA-NEAT1 derived from MIF-treated mesenchymal stem cells protected against doxorubicin-induced cardiac senescence through sponging miR-221-3p.

BACKGROUND: The chemotherapy drug doxorubicin (Dox) is widely used for treating a variety of cancers. However, its high cardiotoxicity hampered its clinical use. Exosomes derived from stem cells showed a therapeutic effect against Dox-induced cardiomyopathy (DIC). Previous studies reported that exosomes derived from mesenchymal stem cells (MSCs) pretreated with macrophage migration inhibitory factor (MIF) (exosomeMIF) showed a cardioprotective effect through modulating long noncoding RNAs/microRNAs (lncRNAs/miRs). This study aimed to investigate the role of exosomeMIF in the treatment of DIC. RESULTS: Exosomes were isolated from control MSCs (exosome) and MIF-pretreated MSCs (exosomeMIF). Regulatory lncRNAs activated by MIF pretreatment were explored using genomics approaches. Fluorescence-labeled exosomes were tracked in vitro by fluorescence imaging. In vivo and in vitro, miR-221-3p mimic transfection enforced miR-221-3p overexpression, and senescence-associated ß-galactosidase assay was applied to test cellular senescence. Exosomal delivering LncRNA-NEAT1 induced therapeutic effect in vivo was confirmed by echocardiography. It demonstrated that exosomesMIF recovered the cardiac function and exerted the anti-senescent effect through LncRNA-NEAT1 transfer against Dox. TargetScan and luciferase assay showed that miR-221-3p targeted the Sirt2 3'-untranslated region. Silencing LncRNA-NEAT1 in MSCs, miR-221-3p overexpression or Sirt2 silencing in cardiomyocytes decreased the exosomeMIF-induced anti-senescent effect against Dox. CONCLUSIONS: The results indicated exosomeMIF serving as a promising anti-senescent effector against Dox-induced cardiotoxicity through LncRNA-NEAT1 transfer, thus inhibiting miR-221-3p and leading to Sirt2 activation. The study proposed that exosomeMIF might have the potential to serve as a cardioprotective therapeutic agent during cancer chemotherapy.

Microvascular Decompression Alone without Rhizotomy Is an Effective Way of Treating Glossopharyngeal Neuralgia: Clinical Analysis of 46 Cases.

BACKGROUND: Microvascular decompression (MVD) has been the right choice for glossopharyngeal neuralgia (GPN) patients. However, whether glossopharyngeal/vagal nerve root rhizotomy should be combined with MVD is still controversial. OBJECTIVE: To evaluate whether glossopharyngeal/vagal nerve root rhizotomy during MVD is necessary for the treatment of GPN. METHODS: We performed a retrospective study of 46 GPN patients who underwent MVD surgery alone in our hospital, and their patient demographics, clinical presentations, and intraoperative findings are shown. The immediate and long-term follow-up outcomes were investigated to show the treatment's efficiency and safety; the outcome was also compared with our previous study. The relevant literature was reviewed to show complications for GPN patients undergoing glossopharyngeal/vagal nerve root rhizotomy with MVD. RESULTS: The most common offending vessel was the posterior inferior cerebellar artery (60.9%). 100% of the patients were pain-free (score of I on the Barrow Neurological Institute pain intensity [BNI-P] scale) immediately after MVD surgery, while 1 patient relapsed with occasional pain 12 months after the operation (score of III on the BNI-P scale). Poor wound healing and hearing loss were found in 1 case each. No complications related to the glossopharyngeal nerve/vagal nerve were reported. Some surgical techniques, such as thorough exploration of the CN IX-X rootlets, full freeing from arachnoid adhesions, and usage of a moist gelatin sponge, can improve the success rate of the operation. CONCLUSIONS: MVD alone without rhizotomy is an effective and safe method for patients with GPN.