Improved CaP Nanoparticles for Nucleic Acid and Protein Delivery to Neural Primary Cultures and Stem Cells.

Efficiently delivering exogenous materials into primary neurons and neural stem cells (NSCs) has long been a challenge in neurobiology. Existing methods have struggled with complex protocols, unreliable reproducibility, high immunogenicity, and cytotoxicity, causing a huge conundrum and hindering in-depth analyses. Here, we establish a cutting-edge method for transfecting primary neurons and NSCs, named teleofection, by a two-step process to enhance the formation of biocompatible calcium phosphate (CaP) nanoparticles. Teleofection enables both nucleic acid and protein transfection into primary neurons and NSCs, eliminating the need for specialized skills and equipment. It can easily fine-tune transfection efficiency by adjusting the incubation time and nanoparticle quantity, catering to various experimental requirements. Teleofection's versatility allows for the delivery of different cargos into the same cell culture, whether simultaneously or sequentially. This flexibility proves invaluable for long-term studies, enabling the monitoring of neural development and synapse plasticity. Moreover, teleofection ensures the consistent and robust expression of delivered genes, facilitating molecular and biochemical investigations. Teleofection represents a significant advancement in neurobiology, which has promise to transcend the limitations of current gene delivery methods. It offers a user-friendly, cost-effective, and reproducible approach for researchers, potentially revolutionizing our understanding of brain function and development.

Dysregulated proteostasis network in neuronal diseases.

Long-term maintenance of synaptic connections is important for brain function, which depends on varying proteostatic regulations to govern the functional integrity of neuronal proteomes. Proteostasis supports an interconnection of pathways that regulates the fate of proteins from synthesis to degradation. Defects in proteostatic signaling are associated with age-related functional decline and neurodegenerative diseases. Recent studies have advanced our knowledge of how cells have evolved distinct mechanisms to safely control protein homeostasis during synthesis, folding and degradation, and in different subcellular organelles and compartments. Neurodegeneration occurs when these protein quality controls are compromised by accumulated pathogenic proteins or aging to an irreversible state. Consequently, several therapeutic strategies, such as targeting the unfolded protein response and autophagy pathways, have been developed to reduce the burden of misfolded proteins and proved useful in animal models. Here, we present a brief overview of the molecular mechanisms involved in maintaining proteostatic networks, along with some examples linking dysregulated proteostasis to neuronal diseases.

Adipocytes play an etiological role in the podocytopathy of high-fat diet-fed rats.

Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P < 0.05) and the urine protein/creatinine ratio were significantly higher (1.76 ± 0.22 vs 1.09 ± 0.15, P < 0.05), increased kidney weight (3.54 ± 0.04 g vs 3.38 ± 0.04 g, P < 0.05) and the glomerular volume and podocyte effacement increased by electron microscopy. Increased renal expression of desmin and decreased renal expression of CD2AP and nephrin were also seen in the HF diet group (P < 0.05). Furthermore, we found that adipocyte-conditioned medium-treated podocytes showed increased desmin expression and decreased CD2AP and nephrin expression compared with that in preadipocyte-conditioned medium-treated controls (P < 0.05). These findings show that adipocyte-derived factor(s) can modulate renal function. Adipocyte-derived factors play an important role in obesity-related podocytopathy.

Kinesio taping and manual pressure release: Short-term effects in subjects with myofasical trigger point.

STUDY DESIGN: Randomized controlled trial. INTRODUCTION: Myofascial pain syndrome is characterized by myofascial trigger points (MTrPs) and fascia tenderness. PURPOSE OF THE STUDY: We investigated the effects of manual pressure release (MPR) alone or in combination with taping (MPR/MKT) in subjects with MTrPs. METHODS: Fifteen and 16 subjects received MPR and MPR/MKT respectively. Outcomes including Pressure pain threshold, muscle stiffness, mechanomyography were assessed at baseline, post-intervention and 7-days later. RESULTS: Pressure pain threshold improved significantly (d = 1.79, p < 0.005) in both groups. Significant improvement in muscle stiffness in the MPR/MKT group (0.27-0.49 mm) as compared to the MPR group (-0.02-0.23 mm). Mechanomyography amplitude in the MPR/MKT group was significantly higher than that of the MPR group (p < 0.05). CONCLUSION: MPR and MPR/MKT are effective in reducing pain in these subjects. MPR/MKT has a greater effect on muscle stiffness and contraction amplitude. LEVEL OF EVIDENCE: IV.

Shoulder physical activity, functional disability and task difficulties in patients with stiff shoulders: interpretation from RT3 accelerator.

We determined whether the degree of symptom-related functional disability was related to daily physical activity of the shoulder in subjects with stiff shoulders (SSs). Responsiveness and a clinically meaningful level of discrimination between improvement and non-improvement for shoulder physical activity (SPA) were determined. Twenty-six subjects with SSs participated. Shoulder physical activity was assessed by RT3 accelerometers fixed on the humerus during daily 14-h data collection periods twice a week for 2 weeks. A moderate correlation coefficient was found between SPA and functional disability (ß = .47). Based on our cohort design and sample, we suggest that SPA (higher than 101.8 counts, hard-moderate or hard tasks) during daily activity are associated with (with at least 83% probability) non-improvement in an individual with SS. Compared to the non-improvement group, the improvement group had less duration of sedentary activity, less frequency and duration of hard tasks, and more frequency and duration of easy tasks (p < 0.01). Appropriate guidance on shoulder physical activities for subjects with SS is important to consider in rehabilitation strategies for these subjects. In our sample, a hard level of shoulder physical activity and sedentary activity should be cautious for these subjects. Further study is needed to validate therapeutic effect of physical activity on the course of patient improvement in subjects with SSs.

Losartan ameliorates renal injury, hypertension, and adipocytokine imbalance in 5/6 nephrectomized rats.

The mechanisms underlying insulin sensitivity and fat tissue distribution in chronic renal insufficiency remain unclear. Previous studies have shown the benefits of angiotensin II receptor blockers on moderately nourished to well-nourished patients with the metabolic syndrome. The current study explored the effect of losartan, the first selective angiotensin II receptor blocker, on insulin sensitivity and visceral fat tissue distribution in a 5/6 nephrectomized (N) rat model and investigated the expression of adipose tissue adipocytokines. Male Sprague-Dawley rats (200 g to 250 g) were subjected to 5/6 nephrectomy, and the adipocytes isolated from the visceral fat tissues were then studied. Results showed that desmin expression was significantly suppressed and systolic blood pressure was successfully normalized in the losartan-administered (NA) group. The weight of the visceral fat pad remarkably decreased in the N and NA groups (100 mg/500 ml drinking water) compared with the control group. The weight did not decrease further in the NA group compared with the N group. Insulin resistance was more remarkable in the N group compared with the control and NA groups. Moreover, the adipose tissue expression of adiponectin and leptin was downregulated whereas that of resistin was upregulated in the N group compared with the control group. However, the adiponectin, leptin, and resistin adipose tissue expression returned to their basal values in the NA group. These findings indicated that losartan administration ameliorated renal injury, systolic blood pressure, and adipocytokine imbalance of the adipose tissue in chronic renal insufficiency. Insulin sensitivity was not improved.

Resistin induces monocyte-endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression in endothelial cells via p38MAPK-dependent pathway.

Resistin, firstly reported as an adipocyte-specific hormone, is suggested to be an important link between obesity and diabetes. Recent studies have suggested an association between resistin and atherogenic processes. The adhesion of circulating monocytes to endothelial cells is a critical step in the early stages of atherosclerosis. The purpose of the present study was to investigate the effect of resistin on the adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. Our results showed that resistin caused a significant increase in monocyte adhesion. In exploring the underlying mechanisms of resistin action, we found that resistin-induced monocyte adhesion was blocked by inhibition of p38MAPK activation using SB203580 and SB202190. Furthermore, resistin increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by HUVECs and these effects were also p38MAPK-dependent. Resistin-induced monocyte adhesion was also blocked by monoclonal antibodies against ICAM-1 and VCAM-1. Taken together, these results show that resistin increases both the expression of ICAM-1 and VCAM-1 by endothelial cells and monocyte adhesion to HUVECs via p38MAPK-dependent pathways.

Acute interstitial nephritis and pigmented tubulopathy in a patient after wasp stings.

Acute renal failure (ARF) is an unusual complication of wasp stings and mostly results from toxic-ischemic acute tubular necrosis. This patient, who was stung by a swarm of wasps, experienced an allergic reaction, rhabdomyolysis, intravascular hemolysis, and subsequent ARF. The originality of this case report is related to the finding of combined lesions of acute tubulointerstitial nephritis and acute tubular nephropathy. From our extensive literature review, it is the first case of a patient developing this type of injury after wasp stings, and the complications have been documented previously only in one form or another. Renal biopsy should be encouraged, especially for a patient with delayed recovery of renal function after wasp stings, to facilitate early steroid treatment for the patient with the histological change of acute interstitial nephritis. Early use of steroid therapy may hasten renal recovery by preventing the development of interstitial fibrosis.

Tacrolimus-associated hemolytic uremic syndrome: a case analysis.

BACKGROUND: Tacrolimus is an effective organ transplantation immunosuppressant. Hemolytic uremic syndrome (HUS) is a rare but severe complication of tacrolimus. METHODS: We report a case of tacrolimus-associated HUS and review the 15 previously reported cases. RESULTS: The results of the 16 cases indicated that tacrolimus-associated HUS is more frequent in females (56.3%), with the mean age at onset of 41.3 years. Forty-four percent of cases received renal transplantations. The average time from the first tacrolimus dose to HUS onset was 7.1 months. Prevalence was between 0.14.7%. The tacrolimus trough level did not predict the prognosis. Seven patients (43.7%) had improved graft function after treatment, including anticoagulation and antiplatelet therapy, reduction or discontinuation of tacrolimus, switch to cyclosporine (CyA), plasma exchange (PE) and dialysis. Five patients (31.3%) died and four patients (25%) lost their graft in spite of the above treatment. Mortality risk factors for transplant recipients with tacrolimus-associated HUS included: (1) non-renal transplant recipients (100% vs. 36.4%, p = 0.034); (2) lower peak serum Cr (2.58 +/- 1.23 vs. 6.16 +/- 1.96, p < 0.002); (3) liver dysfunction (60% vs. 0, p < 0.02); (4) higher serum lactate dehydrogenase (LDH) level (3119 +/- 1019 vs. 982 +/- 522, p < 0.001). A lower platelet count carried borderline mortality risk (29500 +/- 14480 vs. 59625 +/- 25584, p = 0.057). CONCLUSIONS: HUS should be included in the differential diagnosis of renal function deterioration in patients on tacrolimus post-organ transplantation. Frequent renal function monitoring and appropriate treatment should be performed aggressively to decrease morbidity and mortality, especially in patients with risk factors.