Pterostilbene nanoemulsion promotes Nrf2 signaling pathway to downregulate oxidative stress for treating Alzheimer's disease.

Pterostilbene, a stilbene compound, demonstrates neuroprotective effects through its antioxidant and anti-inflammatory properties. However, pterostilbene exhibits low bioavailability. We developed a pterostilbene nanoemulsion with better release stability and particle size. Behavioral tests, including the Y maze, new object recognition, and water maze, revealed that the pterostilbene nanoemulsion demonstrated a more significant effect on improving learning and memory function than pterostilbene. Immunofluorescence analysis revealed that pterostilbene nanoemulsion was more potent in safeguarding hippocampal neurons and inhibiting apoptosis and oxidative stress than pterostilbene. Further results from the Western blot and quantitative reverse transcription polymerase chain reaction indicated that the enhanced efficacy of pterostilbene nanoemulsion may be attributed to its stronger promotion of the nuclear factor erythroid 2-related factor 2 signaling pathway. Hence, enhanced drug delivery efficiency decreased dosage requirements and increased the bioavailability of pterostilbene, thereby potentially providing a safe, effective, and convenient treatment option for patients with Alzheimer's disease.

Cedrol-loaded dissolvable microneedles based on flexible backing for promoting hair growth.

OBJECTIVES: The dissolvable microneedles loaded with cedrol based on flexible backing were developed to deliver cedrol directly and continuously to the dermis, where the drug concentration in the hair follicle can be increased locally. METHODS: The tip-layer matrix solution was prepared by mixing cedrol and polyvinylpyrrolidone K25 (PVP K25), and the pedestal matrix solution was prepared with aqueous hyaluronic acid. The cedrol-loaded dissolvable microneedles (cedrol-DMNs) were prepared under vacuum conditions. The mechanical properties, pig skin penetration efficiency, in vitro cutaneous permeation test, and the amount of drug in the skin and receptor chamber were evaluated. Pharmacodynamical studies were performed with C57BL/6 mice. RESULTS: The mechanical properties of cedrol-DMNs were good. In vitro cutaneous permeation tests and pharmacodynamical studies demonstrated that cedrol-DMN could efficiently deliver the drug to the deep dermis and effectively promote hair growth. CONCLUSIONS: The cedrol-DMNs offer a promising strategy for treating patients suffering from hair loss.

Outcomes of decompressive craniectomy for large territory cerebral infarction with and without prior reperfusion: a multicentre retrospective review.

PURPOSE: Reperfusion therapy has greatly improved outcomes of ischaemic stroke but remains associated with haemorrhagic conversion and early deterioration in a significant proportion of patients. Outcomes in terms of function and mortality are mixed and the evidence for decompressive craniectomies (DC) in this context remains sparse. We aim to investigate the clinical efficacy of DC in this group of patients compared to those without prior reperfusion therapy. METHODS: A multicentre retrospective study was conducted between 2005 and 2020, and all patients with DC for large territory infarctions were included. Outcomes in terms of inpatient and long-term modified Rankin scale (mRS) and mortality were assessed at various time points and compared using both univariable and multivariable analyses. Favourable mRS was defined as 0-3. RESULTS: There were 152 patients included in the final analysis. The cohort had a mean age of 57.5 years and median Charlson comorbidity index of 2. The proportion of preoperative anisocoria was 15.1%, median preoperative Glasgow coma scale was 9, the ratio of left-sided stroke was 40.1%, and ICA infarction was 42.8%. There were 79 patients with prior reperfusion and 73 patients without. After multivariable analysis, the proportion of favourable 6-month mRS (reperfusion, 8.2%; no reperfusion, 5.4%) and 1-year mortality (reperfusion, 26.7%; no reperfusion, 27.3%) were similar in both groups. Subgroup analysis of thrombolysis and/or thrombectomy against no reperfusion was also unremarkable. CONCLUSION: Reperfusion therapy prior to DC performed for large territory cerebral infarctions does not affect the functional outcome and mortality in a well-selected patient population.

Long-Term Survival and Prognostic Factors After Laparoscopic Radical Nephrectomy.

Purpose: Our study aims to investigate the long-term survival and prognostic factors of patients after laparoscopic radical nephrectomy. Methods: Totally, 245 patients with renal cell carcinoma in our hospital from January 2015 to February 2017 were analyzed retrospectively. The 5-year survival status of patients with renal cell carcinoma was under analysis and further based on univariate analysis, and its influencing factors were analyzed by Cox regression. Results: The average 5-year follow-up time of 245 patients with renal cell carcinoma was (4.88 ± 0.52) years. The mortality of 1 year, 3 years and 5 years were 2.45% (5/245), 6.35% (16/245) and 9.80% (24/245), respectively. The survival rates were 97.55% (239/245), 93.06% (228/245) and 90.61% (222/245). Univariate analysis showed that age, tumor diameter, hematuria, TNM stage and postoperative recurrence may be the influencing factors of 5-year survival of patients with renal cell carcinoma (P < .05). However, the following parameters, including gender, course of disease, and other clinical complications were not related to the 5-year survival of patients with renal cell carcinoma (P > .05). the influencing factors of 5-year survival status of patients with renal cell carcinoma were age, tumor diameter, hematuria, TNM stage, and postoperative recurrence. Conclusion: The study revealed the long-term survival of patients with renal cell carcinoma may be associated with age, tumor diameter, hematuria, TNM stage and postoperative recurrence.

Advances in microneedles research based on promoting hair regrowth.

Alopecia is the most common and difficult-to-treat hair disorder. It usually brings a significant psychological burden to the patients. With the growing popularity of alopecia, the study of alopecia has gained more attention. Currently, only minoxidil and finasteride have been approved by the FDA for the treatment of alopecia, but the efficacy has always been unsatisfactory. As a new form of transdermal drug delivery, microneedles have been widely used in the treatment of alopecia and have proven to be effective. Microneedles delivery can improve the efficiency of local drug delivery and patients' compliance, which can achieve better therapeutic effects on hair-related diseases. Therefore, microneedles have gained much attention in the field of alopecia and hair regrowth promotion in recent years. This review summarizes the last decade of research on the microneedles delivery design for the treatment of alopecia or promotion of hair regrowth and provides a comprehensive evaluation of this field.

Clinical Outcomes After Ventriculo-Peritoneal Shunting in Patients With Classic vs. Complex NPH.

Objective: Normal pressure hydrocephalus (NPH) is a neurological condition characterized by a clinical triad of gait disturbance, cognitive impairment, and urinary incontinence in conjunction with ventriculomegaly. Other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and vascular dementia share some overlapping clinical features. However, there is evidence that patients with comorbid NPH and Alzheimer's or Parkinson's disease may still exhibit good clinical response after CSF diversion. This study aims to evaluate clinical responses after ventriculo-peritoneal shunt (VPS) in a cohort of patients with coexisting NPH and neurodegenerative disease. Methods: The study has two components; (i) a pilot study was performed that specifically focused upon patients with Complex NPH and following the inclusion of the Complex NPH subtype into consideration for the clinical NPH programme, (ii) a retrospective snapshot study was performed to confirm and characterize differences between Classic and Complex NPH patients being seen consecutively over the course of 1 year within a working subspecialist NPH clinic. We studied the characteristics of patients with Complex NPH, utilizing clinical risk stratification and multimodal biomarkers. Results: There was no significant difference between responders and non-responders to CSF diversion on comorbidity scales. After VPS insertion, significantly more Classic NPH patients had improved cognition compared to Complex NPH patients (p = 0.005). Improvement in gait and urinary symptoms did not differ between the groups. 26% of the Classic NPH group showed global improvement of the triad, and 42% improved in two domains. Although only 8% showed global improvement of the triad, all Complex NPH patients improved in gait. Conclusions: Our study has demonstrated that the presence of neurodegenerative disorders co-existing with NPH should not be the sole barrier to the consideration of high-volume tap test or lumbar drainage via a specialist NPH programme. Further characterization of distinct cohorts of NPH with differing degrees of CSF responsiveness due to overlay from neurodegenerative or comorbidity risk burden may aid toward more precise prognostication and treatment strategies. We propose a simplistic conceptual framework to describe NPH by its Classic vs. Complex subtypes to promote the clinical paradigm shift toward subspecialist geriatric neurosurgery by addressing needs for rapid screening tools at the clinical-research interface.

The Effect on Sodium/Iodide Symporter and Pendrin in Thyroid Colloid Retention Developed by Excess Iodide Intake.

It is well known that excess iodide can lead to thyroid colloid retention, a classic characteristic of iodide-induced goiter. However, the mechanism has not been fully unrevealed. Iodide plays an important role in thyroid function at multiple steps of thyroid colloid synthesis and transport among which sodium/iodide symporter (NIS) and pendrin are essential. In our study, we fed female BALB/c mice with different concentrations of high-iodine water including group A (control group, 0 µg/L), group B (1500 µg/L), group C (3000 µg/L), group D (6000 µg/L), and group E (12,000 µg/L). After 7 months of feeding, we found that excess iodide could lead to different degrees of thyroid colloid retention. Besides, NIS and pendrin expression were downregulated in the highest dose group. The thyroid iodide intake function detected by urine iodine assay and thyroidal (125)I experiments showed that the urine level of iodine increased, while the iodine intake rate decreased when the concentration of iodide used in feeding water increased (all p < 0.05 vs. control group). In addition, transmission electron microscopy (TEM) indicated a reduction in the number of intracellular mitochondria of thyroid cells. Based on these findings, we concluded that the occurrence of thyroid colloid retention exacerbated by excess iodide was associated with the suppression of NIS and pendrin expression, providing an additional insight of the potential mechanism of action of excess iodide on thyroid gland.