Although several epidemiologic and animal studies have revealed correlations between obesity and neurodegenerative disorders, such as Parkinson disease (PD), the underlying pathological mechanisms of ...obesity-induced PD remain unclear. Our study aimed to assess the effect of diet-induced obesity on the brain dopaminergic pathway. For five months, starting from weaning, we gave C57BL/6 mice a high-fat diet (HFD) to generate an obese mouse model and investigate whether the diet reprogrammed the midbrain dopaminergic system. Tyrosine hydroxylase staining showed that the HFD resulted in fewer dopaminergic neurons in the substantia nigra (SN), but not the striatum. It also induced neuroinflammation, with increased astrogliosis in the SN and striatum. Dendritic spine density in the SN of HFD-exposed mice decreased, which suggested that prolonged HFD altered dopaminergic neuroplasticity. All three peroxisome proliferator-activated receptor (PPAR) subtype (PPAR-α, PPAR-β/δ, PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area of HFD mice when compared to those in controls. This study showed that a prolonged HFD induced neuroinflammation, suppressed PPAR levels, caused degeneration of midbrain dopaminergic neurons, and resulted in symptoms reminiscent of human PD. To our knowledge, this is the first study documenting the effects of an HFD on PPARs in dopaminergic neurons.
Background and Aim
Reducing post‐absorptive (fasting) phase by eating late evening snacks (LESs) is a potential intervention to improve substrate utilization and reverse sarcopenia. This study ...analyzed the results of published randomized controlled trials and controlled clinical trials to evaluate the effects of LES on liver function of patients with cirrhosis.
Methods
A meta‐analysis was conducted. The search strategy included electronic database searches, and 300 articles were searched. Eight of these articles provided qualified data for pooling and analysis. Outcomes assessments included serum albumin, total bilirubin, alanine aminotransferase, prothrombin time, and aspartate aminotransferase, complications of cirrhosis, severity of liver disease, and blood glucose levels.
Results
Our analysis included eight studies comprising 341 patients (167 in LES groups and 174 in control groups). The results showed that LES intervention helped to maintain liver reserves. These eight studies demonstrated that LES intervention had significant effects for liver biochemical parameters on albumin, ammonia, and prothrombin time, with respective effect sizes of 0.233, −0.425, and −0.589; liver enzymes include aspartate aminotransferase and alanine aminotransferase, with respective effect sizes of −0.320 and −0.284. Studies on clinical signs of liver dysfunction showed lower occurrence rates of ascites and hepatic encephalopathy than in the control group. LES had no significant effect on Child–Pugh score.
Conclusions
The overall results of the meta‐analysis indicated that having LES can improve liver function reserve for patients with liver cirrhosis, with or without hepatocellular carcinoma. LES is a promising intervention for reversing anabolic resistance and the sarcopenia of cirrhosis, resulting in an improved quality of life for patients with cirrhosis.
Few studies have discussed the disease nature and treatment outcomes for bilateral cavernous sinus dural arteriovenous fistula (CSDAVF). This study aimed to investigate the clinical features and ...treatment outcomes of bilateral CSDAVF. Embase, Medline, and Cochrane library were searched for studies that specified the outcomes of bilateral CSDAVF from inception to April 2022. The classification, clinical presentation, angiographic feature, surgical approach, and treatment outcomes were collected. Meta-analysis was performed using the random effects model. Eight studies reporting 97 patients were included. The clinical presentation was mainly orbital (n = 80), cavernous (n = 52) and cerebral (n = 5) symptoms. The most approached surgical route was inferior petrosal sinus (n = 80), followed by superior orbital vein (n = 10), and alternative approach (n = 7). Clinical symptoms of 88% of the patients (95% CI 80-93%, I
= 0%) were cured, and 82% (95% CI 70-90%, I
= 7%) had angiographic complete obliteration of fistulas during follow up. The overall complication rate was 18% (95% CI 11-27%, I
= 0%). Therefore, endovascular treatment is an effective treatment for bilateral CSDAVF regarding clinical or angiographic outcomes. However, detailed evaluation of preoperative images and comprehensive surgical planning of the approach route are mandatory owing to complexity of the lesions.
Background Oligoprogression is an emerging issue in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the surgical treatment for central ...nervous system (CNS) oligoprogression is not widely discussed. We investigated the outcomes of craniotomy with adjuvant whole-brain radiotherapy (WBRT) and subsequent therapies for CNS oligoprogression in patients with EGFR-mutated NSCLC. Methods NSCLC patients with CNS oligoprogression were identified from a tertiary medical center. The outcomes of surgery with adjuvant WBRT or WBRT alone were analyzed, along with other variables. Overall survival and progression-free survival were analyzed using the log-rank test as the primary and secondary endpoints. A COX regression model was used to identify the possible prognostic factors. Results Thirty-seven patients with CNS oligoprogression who underwent surgery or WBRT were included in the study after reviewing 728 patients. Twenty-one patients underwent surgery with adjuvant WBRT, and 16 received WBRT alone. The median overall survival for surgery and WBRT alone groups was 43 (95% CI 17-69) and 22 (95% CI 15-29) months, respectively. Female sex was a positive prognostic factor for overall survival (OR 0.19, 95% CI 0.06-0.57). Patients who continued previous tyrosine kinase inhibitors (OR 3.48, 95% CI 1.06-11.4) and induced oligoprogression (OR 3.35, 95% CI 1.18-9.52) were associated with worse overall survival. Smoking history (OR 4.27, 95% CI 1.54-11.8) and induced oligoprogression (OR 5.53, 95% CI 2.1-14.7) were associated with worse progression-free survival. Conclusions Surgery combined with adjuvant WBRT is a feasible treatment modality for CNS oligoprogression in patients with EGFR-mutated NSCLC. Changing the systemic-targeted therapy after local treatments may be associated with improved overall survival. Keywords: Non-small cell lung cancer, Oligoprogression, Oligometastasis, Tyrosine kinase inhibitor, Metastasis, Metastatic brain tumors
The incidence of brain metastasis (BM) from colorectal cancer (CRC) is increasing. This study aims to identify the clinical prognosticators and evaluate the prognostic validity of common comorbidity ...indices in patients with BM from CRC. This retrospective single‐center study analyzed 93 patients with BM from CRC who received surgical excision and/or radiotherapy. The clinical characteristics and prognostic indices including the 5‐item modified frailty index (mFI‐5) and prognostic nutritional index (PNI) were calculated from the collected patient data and analyzed. In this study, 66 (71.0%), 10 (10.8%), and 17 (18.3%) patients received whole‐brain radiotherapy (WBRT) alone, surgery alone, and surgery plus WBRT, respectively. The median survival of all patients was 3.98 months (IQR: 1.74–7.99). The 2‐ and 3‐year survival rates were 7.4% and 3.7%, respectively. Controlled primary tumor (p = 0.048), solitary BM (p = 0.001), surgery + radiation (p < 0.001), and greater PNI (p = 0.001) were independent predictors of favorable survival. In surgically treated patients, uncontrolled primary tumor (p = 0.006), presence of multiple BM (p < 0.001), and MFI‐5 ≥ 2 (p = 0.038) were independent prognosticators. For patients who received WBRT, the presence of two (p = 0.004) or multiple (p < 0.001) BM and PNI (p < 0.001) were independent survival predictors MFI‐5, multiple BM, and the status of the primary tumor were independent prognosticators for patients who underwent surgery for CRCBM. For patients who received WBRT, the PNI and the number of BM were independent survival predictors.
Functional restoration is an important issue in the treatment of traumatic brain injury (TBI). Various electrical stimulation devices and protocols have been applied in preclinical studies and have ...shown therapeutic potential for brain trauma. Short-term invasive cortical electrical stimulation during the acute stage of TBI might be a feasible adjuvant therapy for patients with moderate-to-severe brain injury receiving neurosurgical treatment in the intensive care unit. However, the therapeutic effects of short-term multisession cortical electrical stimulation for brain trauma are not clear. This study explored the therapeutic effects of acute-stage short-term cortical electrical stimulation on TBI. We conducted seven sessions of one-hour cortical electrical stimulation from day 0 to day 6 in rats after brain trauma by controlled cortical impact and then evaluated the functional outcome and histopathological changes. Our data showed that short-term cortical electrical stimulation improved motor coordination, short-term memory, and learning ability and attenuated neurological severity after brain trauma. Lesion volume, apoptosis, and gliosis after brain trauma were reduced, and trauma-induced neurogenesis in the hippocampus for the innate neural reparative response was increased. Our study demonstrated that short-term cortical electrical stimulation applied in the acute stage of traumatic brain injury is a potential adjuvant therapy to improve the recovery of neurological deficits.
Objective:
Ischemic stroke is an important cause of death and disability worldwide. Early reperfusion by thrombolysis or thrombectomy has improved the outcome of acute ischemic stroke. However, the ...therapeutic window for reperfusion therapy is narrow, and adjuvant therapy for neuroprotection is demanded. Electrical stimulation (ES) has been reported to be neuroprotective in many neurological diseases. In this study, the neuroprotective effect of early somatosensory cortical ES in the acute stage of ischemia/reperfusion injury was evaluated.
Methods:
In this study, the rat model of transient middle cerebral artery occlusion was used to explore the neuroprotective effect and underlying mechanisms of direct primary somatosensory (S1) cortex ES with an electric current of 20 Hz, 2 ms biphasic pulse, 100 μA for 30 min, starting at 30 min after reperfusion.
Results:
These results showed that S1 cortical ES after reperfusion decreased infarction volume and improved functional outcome. The number of activated microglia, astrocytes, and cleaved caspase-3 positive neurons after ischemia/reperfusion injury were reduced, demonstrating that S1 cortical ES alleviates inflammation and apoptosis. Brain-derived neurotrophic factor (BDNF) and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were upregulated in the penumbra area, suggesting that BDNF/TrkB signals and their downstream PI3K/Akt signaling pathway play roles in ES-related neuroprotection.
Conclusion:
This study demonstrates that somatosensory cortical ES soon after reperfusion can attenuate ischemia/reperfusion injury and is a promising adjuvant therapy for thrombolytic treatment after acute ischemic stroke. Advanced techniques and devices for high-definition transcranial direct current stimulation still deserve further development in this regard.
Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) ...proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.
Genipin, a natural compound derived from the fruit of
, possesses numerous biological properties. The aim of the present study was to investigate the anticancer effects of genipin in human bladder ...cancer. T24 and 5637 bladder cancer cells were treated with different concentrations of genipin (0-200 µM) and tested for cell viability, colony formation, cell cycle progression and apoptosis. A xenograft model of bladder cancer was established to determine the anticancer effect of genipin
. The involvement of the phosphoinositide-3 kinase (PI3K)/Akt pathway in the action of genipin was examined. Genipin treatment significantly inhibited the viability and clonogenic growth of bladder cancer cells and inhibited the growth of T24 xenograft tumors, compared with vehicle controls (P<0.05). Genipin-treated cells exhibited a cell cycle arrest at the G0/G1-phase, which was accompanied by a deregulation of numerous cell cycle regulators. Genipin-treated cells demonstrated a significant increase in the percentage of apoptotic cells, loss of mitochondrial membrane potential, Bax translocation to the mitochondria and the release of cytochrome
to the cytosol. Additionally, genipin treatment significantly (P<0.05) reduced the phosphorylation levels of PI3K and Akt in bladder cancer cells. Importantly, genipin-mediated anticancer effects were reversed by the overexpression of constitutively active Akt. In conclusion, to the best of our knowledge, the present study demonstrates for the first time the growth inhibitory effects of genipin in bladder cancer cells, and indicates its potential as a natural anticancer agent for bladder cancer.
Background:
Wingspan stent has gained interest for better long-term outcomes for intracranial atherosclerosis disease (ICAD). However, in-stent restenosis still presents as a problem and may cause ...postoperative neurological events. We aimed to find a way to prevent in-stent restenosis.
Method:
Patients with stenosis >70% ICAD were treated with wingspan stent and were retrospectively reviewed. The patients were separated into two groups: one with post-dilation and the other without post-dilation. The outcomes of wingspan stenting were compared immediately after the surgery and at a 1-year follow-up.
Results:
Overall, 28 patients were included for analysis, with 15 patients undergoing post-dilation and 13 patients not undergoing the procedure. The extent of stenosis was significantly lower in the post-dilation group than in the no post-dilation group, both immediately after the surgery (14.8 ± 10.2 vs. 28.5 ± 14.5%,
p
< 0.01) and at 1-year follow-up (25.8 ± 18.0 vs. 50.1 ± 23.2%,
p
< 0.01). The post-dilation method immediately expanded the stent diameter (2.89 ± 0.48 vs. 3.05 ± 0.44 mm,
p
< 0.001), and the diameter still increased at 1-year follow-up (3.05 ± 0.44 vs. 3.12 ± 0.43 mm,
p
< 0.01) due to the self-expandable property of the wingspan. Similarly, in the no post-dilation group, the stent size was also increased (2.70 ± 0.67 vs. 2.80 ± 0.64 mm
, p
< 0.01). However, at 1-year follow up, the luminal diameter was stationary in the post-dilation group (2.36 ± 0.73 vs. 2.46 ± 0.82 mm,
p
= 0.88) and decreased in the no post-dilation group (2.24 ± 0.56 vs. 1.60 ± 0.79 mm,
p
< 0.01). The periprocedural complication rate was similar between the groups.
Conclusion:
The post-dilation method can be feasibly performed and can offer better stent expansion and apposition in the wingspan system. By applying this technique, we might prevent in-stent restenosis and improve neurological outcomes.
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