Injectable hydrogel-based combination therapy for myocardial infarction: a systematic review and Meta-analysis of preclinical trials.

INTRODUCTION: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. PATIENT CONCERNS: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. DIAGNOSIS: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). INTERVENTIONS: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. OUTCOMES: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. CONCLUSION: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation.

Multifunctional biomaterial platforms for blocking the fibrosis process and promoting cellular restoring effects in myocardial fibrosis therapy.

Myocardial fibrosis is the result of abnormal healing after acute and chronic myocardial damage and is a direct cause of heart failure and cardiac insufficiency. The clinical approach is to preserve cardiac function and inhibit fibrosis through surgery aimed at dredging blood vessels. However, this strategy does not adequately address the deterioration of fibrosis and cardiac function recovery. Therefore, numerous biomaterial platforms have been developed to address the above issues. In this review, we summarize the existing biomaterial delivery and restoring platforms, In addition, we also clarify the therapeutic strategies based on biomaterial platforms, including general strategies to block the fibrosis process and new strategies to promote cellular restoring effects. The development of structures with the ability to block further fibrosis progression as well as to promote cardiomyocytes viability should be the main research interests in myocardial fibrosis, and the reestablishment of structures necessary for normal cardiac function is central to the treatment of myocardial fibrosis. Finally, the future application of biomaterials for myocardial fibrosis is also highlighted.

The Neuroprotective Effect of Byu d Mar 25 in LPS-Induced Alzheimer's Disease Mice Model.

Inflammatory factors play an important role in the pathogenesis of Alzheimer's disease (AD). Byu d Mar 25 (BM25) has been suggested to have protective effects in the central nervous system. However, the effect of BM25 on AD has not been determined. This study aims to investigate the neuroprotective effect of BM25 in AD. A total of 40 AD model mice were randomly assigned to the following five groups (n = 8 per group): the AD + NS group, the AD + donepezil group, and three AD + BM25 groups treated with either 58.39 mg/kg (AD + BM25-L), 116.77 mg/kg (AD + BM25-M), or 233.54 mg/kg BM25 (AD + BM25-H). The Morris water maze test was performed to assess alterations in spatial learning and memory deficits. Nissl staining was performed to detect Nissl bodies and neuronal damage. The expression of IL-1ß and TNF-α was evaluated by ELISA. The protein expression of P-P38, P38, P-IκBα, caspase 1, COX2, and iNOS was determined by western blotting. The expression of Aß, p-Tau, and CD11b was measured by immunohistochemistry. The mRNA expression levels of IL-1ß, TNF-α, COX2, and iNOS were measured by qRT-PCR. Spatial memory significantly improved in the AD + BM25-M and AD + BM25-H groups compared with the AD + NS group (p < 0.05). The expression of Aß and p-Tau significantly decreased in the AD + BM25-M and AD + BM25-H groups (p < 0.05). The neuron density and hierarchy and number of pyramidal neurons significantly increased in the AD + BM25-M and AD + BM25-H groups (p < 0.05). In addition, the expression levels of CD11b, IL-1ß, TNF-α, COX2, iNOS, caspase 1, p-IκBα, and p-P38 significantly decreased in the AD + BM25-M and AD + BM25-H groups (p < 0.05). In conclusion, our findings suggest that BM25 may exert anti-inflammatory and neuroprotective effects in AD model mice by suppressing the activity of microglia and inhibiting the phosphorylation of IκBα and p38 MAPK.

Influence of high-altitude hypoxic environments on the survival of cochlear hair cells and spiral ganglion neurons in rats.

The aim of the present study was to observe the histological changes in the peripheral auditory system in rats at different time-points after relocating from low altitude to high altitude (3,600 m). The general physical condition of the rats was observed and cochlear tissue samples were obtained every month. The morphology and survival of the cochlear hair cells (HCs) were observed using cochlear surface preparation at 1, 30, 90, 120, 150 and 180 days after moving to the plateau area. Changes in spiral ganglion neurons (SGNs) were detected at different time-points using immunofluorescence technology on frozen sections. No obvious morphological changes were observed in the cochlear HCs within 1-3 months of the rats moving to the plateau area, and there was little loss of outer HCs (OHCs) at 3 months. Cell swelling, dislocation and loss of cochlear OHCs were apparent at 4 months, and the losses of cochlear OHCs and inner HCs (IHCs) were 54 and 39%, respectively at 6 months. The loss of SGNs was observed at 3 months, and there was a loss of 28-35% of SGNs during 3-6 months. Thus, a high-altitude hypoxic environment influenced the cochlear HCs in rats after moving to the plateau area in a time-dependent manner. The damage to SGNs occurred earlier than the HCs, although SGN damage was not aggravated with time. Furthermore, compared with cochlear HCs, cochlear SGNs were identified to be markedly more sensitive to hypoxia, and exerted an adaptive mechanism to protect neurons from hypoxia.