EDomics: a comprehensive and comparative multi-omics database for animal evo-devo.

Evolutionary developmental biology (evo-devo) has been among the most fascinating interdisciplinary fields for decades, which aims to elucidate the origin and evolution of diverse developmental processes. The rapid accumulation of omics data provides unprecedented opportunities to answer many interesting but unresolved evo-devo questions. However, the access and utilization of these resources are hindered by challenges particularly in non-model animals. Here, we establish a comparative multi-omics database for animal evo-devo (EDomics, http://edomics.qnlm.ac) containing comprehensive genomes, bulk transcriptomes, and single-cell data across 40 representative species, many of which are generally used as model organisms for animal evo-devo study. EDomics provides a systematic view of genomic/transcriptomic information from various aspects, including genome assembly statistics, gene features and families, transcription factors, transposable elements, and gene expressional profiles/networks. It also exhibits spatiotemporal gene expression profiles at a single-cell level, such as cell atlas, cell markers, and spatial-map information. Moreover, EDomics provides highly valuable, customized datasets/resources for evo-devo research, including gene family expansion/contraction, inferred core gene repertoires, macrosynteny analysis for karyotype evolution, and cell type evolution analysis. EDomics presents a comprehensive and comparative multi-omics platform for animal evo-devo community to decipher the whole history of developmental evolution across the tree of life.

MolluscDB: an integrated functional and evolutionary genomics database for the hyper-diverse animal phylum Mollusca.

Mollusca represents the second largest animal phylum but remains poorly explored from a genomic perspective. While the recent increase in genomic resources holds great promise for a deep understanding of molluscan biology and evolution, access and utilization of these resources still pose a challenge. Here, we present the first comprehensive molluscan genomics database, MolluscDB (http://mgbase.qnlm.ac), which compiles and integrates current molluscan genomic/transcriptomic resources and provides convenient tools for multi-level integrative and comparative genomic analyses. MolluscDB enables a systematic view of genomic information from various aspects, such as genome assembly statistics, genome phylogenies, fossil records, gene information, expression profiles, gene families, transcription factors, transposable elements and mitogenome organization information. Moreover, MolluscDB offers valuable customized datasets or resources, such as gene coexpression networks across various developmental stages and adult tissues/organs, core gene repertoires inferred for major molluscan lineages, and macrosynteny analysis for chromosomal evolution. MolluscDB presents an integrative and comprehensive genomics platform that will allow the molluscan community to cope with ever-growing genomic resources and will expedite new scientific discoveries for understanding molluscan biology and evolution.

An Ex Vivo Study of Filum Terminale in Children and Fetuses Based on Optical Coherence Tomography.

Objective: To distinguish ex vivo normal and abnormal filum terminale (FT) in pathology based on optical coherence tomography (OCT). Methods: A total of 14 ex vivo FTs, freshly imaged via OCT after being cut, were excised from the scanned region for histopathological examination (HPE). Qualitative analysis was performed by 2 blinded assessors. Results: We performed OCT imaging of all specimens and validated them qualitatively. In the fetal FTs, we observed large amounts of fibrous tissue scattered throughout with a few capillaries but no adipose tissue. In tight filum terminale syndrome (TFTS), adipose infiltration and capillaries were significantly increased, with obvious fibroplasia and disarrangement. OCT images showed increased adipose tissue in which the adipocytes were arranged in a grid-like pattern; dense, disordered fibrous tissue and vascular-like tissue were present. The diagnostic results of OCT and HPE were consistent (Kappa = 0.659; P = .009, <.01), and there was no statistically significant difference in diagnosing TFTS using a Chi-square test (P > .05). The area under the curve (AUC) for OCT (AUC = 0.966; 95% CI, 0.903 to 1.000) was better than magnetic resonance imaging (MRI) (AUC = 0.649; 95% CI, 0.403 to 0.896). Conclusion: OCT can quickly obtain clear images of FT's inner structure, contribute to diagnosing TFTS and will be an indispensable complement to MRI and HPE. More FT sample studies in vivo are needed to confirm the high accuracy rate of OCT.

IL-9 blockade attenuates inflammation in a murine model of mechanical ventilation-induced lung injury by inhibiting the NLRP3 inflammasome pathway.

OBJECTIVES: Ventilation-induced lung injury (VILI) causes a huge economic and social burden, and its prevention and treatment have gained increasing attention in recent years. IL-9 is an important inflammatory factor, but its potential role in VILI remains unclear. This study intended to explore whether blocking IL-9 could alleviate VILI and explore its underlying mechanism. METHODS: Lung injury was induced by mechanical ventilation (MV) in C57BL/6 mice. Changes in inflammatory factors and NLRP3-related proteins were assessed using quantitative reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Subsequently, Nlrp3-/- mice were used to further elucidate the underlying mechanism. RESULTS: The percentage of Th9 cells in the peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues of MV mice was increased compared to those of control mice. Treatment with anti-IL-9 mAb significantly alleviated the changes in lung histopathology, wet/dry lung proportion, total protein content, and neutrophil content in BALF induced by VILI. Additionally, administering anti-IL-9 mAb significantly downregulated the expression levels of inflammatory factors in BALF and lung tissues of mice with VILI. In addition, administering anti-IL-9 mAb inhibited NLRP3 inflammasome activation, as evidenced by the observed downregulation of NLRP3, ASC, cleaved caspase-1, and GSDMD-N. Additionally, NLRP3-deficient mice had lower lung injury induced by VILI than wild-type mice. Furthermore, the anti-IL-9 mAb only partially inhibited VILI in Nlrp3-/- mice. CONCLUSIONS: In MV mice, the anti-IL-9 mAb alleviated lung injury and reduced the secretion and expression of inflammatory factors partly by inhibiting the NLRP3 inflammasome pathway.

Tethered cord syndrome with lower back pain and lumbosacral angle increase: case report.

INTRODUCTION: Tethered cord syndrome (TCS) is the progressive development of various neuromuscular dysfunctions caused by the traction of the conus medullaris resulting from congenital or acquired causes, which are often accompanied by fecal and/or urinary incontinence and abnormal sensory motor functions of lower limbs. Lower back pain is a common clinical symptom of TCS patients and can be significantly improved by surgical untethering. However, the specific relationship between the increase in lumbosacral angle and TCS has rarely been reported. PATIENT: A case of TCS in an 8-year-old girl is reported. The patient had lower back pain complicated by increased lumbosacral angle for more than 20 days. DIAGNOSES: Physical examination and MRI results showed that the condition of the child has been complicated by TCS. INTERVENTIONS: After additional relevant examination, surgical untethering of the terminal filum was performed under general anesthesia. OUTCOMES: The symptoms of lower back pain disappeared, and the plain radiographs indicated that the lumbosacral angle decreased and lumbar lordosis returned to normal. During the follow-up period of half a year, the child did not experience particular discomfort or asymptomatic aggravation. CONCLUSIONS: For children with low back pain complicated by lumbosacral angle increase, MRI should be performed to exclude TCS. Once the patient has been diagnosed, early surgical treatment should be provided.

Oridonin synergizes with Nutlin-3 in osteosarcoma cells by modulating the levels of multiple Bcl-2 family proteins.

The small-molecule inhibitors of p53-murine double minute 2 interaction, such as Nutlin-3, are effective against cancers bearing wild-type p53. However, murine double minute 2 inhibitors often are unable to completely eliminate solid tumor cells. To address this issue, we investigated the anticancer effects of Nutlin-3 in combination with Oridonin in osteosarcoma cells. We found that Oridonin at sub-toxic concentrations synergistically enhanced Nutlin-3-mediated cell viability inhibition in wild-type p53 U2OS and SJSA-1, but not in p53-mutant MNNG/HOS and in null-p53 Saos-2 osteosarcoma cell lines. Importantly, in the presence of Oridonin, Nutlin-3 could completely abolish cell viability in the wild-type p53 osteosarcoma cell lines. Western blotting analysis showed that Oridonin treatment rapidly and distinctly increased the levels of all three forms of Bim and also markedly reduced the levels of Bcl-2 and Bcl-xl in osteosarcoma cells. Western blotting analysis further showed that Oridonin considerably enhanced Nutlin-3-triggered activation of caspases-9 and -3 and poly(ADP-ribose) polymerase cleavage. Flow cytometry assay showed that Oridonin significantly enhanced Nutlin-3-mediated apoptosis in wild-type p53 osteosarcoma cells. Overall, our results suggest that the combined treatment of Nutlin-3 plus Oridonin may offer a novel therapeutic strategy for osteosarcoma.

Pan-evolutionary and regulatory genome architecture delineated by an integrated macro- and microsynteny approach.

The forthcoming massive genome data generated by the Earth BioGenome Project will open up a new era of comparative genomics, for which genome synteny analysis provides an important framework. Profiling genome synteny represents an essential step in elucidating genome architecture, regulatory blocks/elements and their evolutionary history. Here we describe PanSyn, ( https://github.com/yhw320/PanSyn ), the most comprehensive and up-to-date genome synteny pipeline, providing step-by-step instructions and application examples to demonstrate its usage. PanSyn inherits both basic and advanced functions from existing popular tools, offering a user-friendly, highly customized approach for genome macrosynteny analysis and integrated pan-evolutionary and regulatory analysis of genome architecture, which are not yet available in public synteny software or tools. The advantages of PanSyn include: (i) advanced microsynteny analysis by functional profiling of microsynteny genes and associated regulatory elements; (ii) comprehensive macrosynteny analysis, including the inference of karyotype evolution from ancestors to extant species; and (iii) functional integration of microsynteny and macrosynteny for pan-evolutionary profiling of genome architecture and regulatory blocks, as well as integration with external functional genomics datasets from three- or four-dimensional genome and ENCODE projects. PanSyn requires basic knowledge of the Linux environment and Perl programming language and the ability to access a computer cluster, especially for large-scale genomic comparisons. Our protocol can be easily implemented by a competent graduate student or postdoc and takes several days to weeks to execute for dozens to hundreds of genomes. PanSyn provides yet the most comprehensive and powerful tool for integrated evolutionary and functional genomics.

Comparison of the size of bilateral testis in children with unilateral non-communicating hydrocele and its correlation with age.

BACKGROUND: Opinions on the optimal age for surgical management of hydroceles in young boys are not uniform. Scrotal ultrasonography can be used to diagnose hydroceles and measure testicular size. A comparison of bilateral testicular size with hydrocele and the change in trend with age has not been reported. We therefore aimed to analyze the bilateral testicular size of children with unilateral non-communicating hydroceles and examine the correlation between age and testicular volume. METHODS: Non-communicating hydrocele cases in children were included. Ultrasound results, age, and diagnose time were retrospectively recorded. The bilateral testicular size was compared, and the correlation between age and testicular volume was analyzed. RESULTS: There were 138 cases of non-communicating hydrocele, ranging in age from 11 to 72 months. The diagnose time ranged from 3 days to 54 months. The volume of the testis on the side of the hydrocele was larger than that on the normal side (P < 0.001). Testicular length was not different bilaterally. Testicular width and height were greater on the hydrocele side than on the normal testicular side (P<0.001). Age was positively correlated with testicular volume on the normal side (P = 0.004) but not on the hydrocele side. CONCLUSIONS: An important finding was that when the contralateral normal testicular volume increases with age, the testicular volume does not increase on the hydrocele side. This finding confirms the adverse effects of hydrocele on testicular growth and provides a basis for early treatment.

Crushing analysis of hierarchical multicellular tubes with gradient character along axial and radial directions under oblique loads.

To overcome the disadvantage of high initial peak crush force (IPCF) in hierarchical and gradient structures, the hierarchical multicellular tubes (HMTs) with gradient character along axial and radial directions are proposed based on the bidirectional structural characters of bamboo stem. Crashworthiness performances of HMTs under oblique loads are systematically studied by using numerical simulation. Results show that compared with the square tube with the same mass, HMTs have higher energy absorption capability under different impact angles. The maximum increases of specific energy absorption (SEA) and crush force efficiency (CFE) reach up to 67.02% and 806%, respectively. Whereas, the maximum decrease of IPCF reaches up to 79.92%. Effects of structural parameters, including hierarchical level, wall thickness and internode space, on the crashworthiness performances of HMTs are also fully investigated.

Advances in genetic factors of adolescent idiopathic scoliosis: a bibliometric analysis.

Objective: This study offers a bibliometric analysis of the current situation, hotspots, and cutting-edge domains of genetic factors of adolescent idiopathic scoliosis (AIS). Methods: All publications related to genetic factors of AIS from January 1, 1992, to February 28, 2023, were searched from the Web of Science. CiteSpace software was employed for bibliometric analysis, collecting information about countries, institutions, authors, journals, and keywords of each article. Results: A cumulative number of 308 articles have been ascertained. Since 2006, publications relating to genetic factors of AIS have significantly increased. China leads in both productivity and influence in this area, with the Chinese Academy of Medical Sciences being the most productive institution. The most prolific scholars in this field are Y. Qiu and Z. Z. Zhu. The publications that contributed the most were from Spine and European Spine Journal. The most prominent keywords in the genetic factors of AIS were "fibrillin gene", "menarche", "calmodulin", "estrogen receptor gene", "linkage analysis", "disc degeneration", "bone mineral density", "melatonin signaling dysfunction", "collagen gene", "mesenchymal stem cell", "LBX1", "promoter polymorphism", "Bone formation", "cerebrospinal fluid flow" and "extracellular matrix". Conclusion: This analysis provides the frontiers and trends of genetic factors in AIS, including relevant research, partners, institutions and countries.

Analysis of trends in testicular atrophy index values with age in patients with unilateral palpable cryptorchidism.

Cryptorchidism affects the growth of testicular volume. Testicular volume is associated with reproductive function. The testicular atrophy index evaluates the degree of damage caused by cryptorchidism, but it remains unclear whether changes in testicular atrophy index are related to age. We selected patients who underwent surgery for unilateral palpable cryptorchidism. Testicular volume was measured using ultrasonography. The testicular atrophy indices of the undescended testes were then reviewed, and their correlation with age was analyzed. We studied 228 cases (age range: 6-53 months). Scatter plots were constructed, and Loess curves were fitted, revealing a turning point at 24 months of age. The patients were divided into age groups of 6-24 months and 25-53 months. The testicular volume of the cryptorchid side was smaller than that of the normal side in both groups (both P < 0.001). In the 6-24-month group, the testicular atrophy index was positively correlated with age, testicular volume on the cryptorchid side was not correlated with age, and testicular volume was positively correlated with age on the normal side. In the 25-53-month group, testicular atrophy index and testicular volumes on either side were not correlated with age. A palpable unilateral cryptorchid testis is smaller than the contralateral testis. The testicular atrophy index increases with age between 6 months and 24 months, but not between 25 months and 53 months. Testicular volume increased with age on the normal side between 6 months and 24 months, but not on the cryptorchid side. Trends in testicular atrophy index with age contribute to the decision of operation time.

Changes in the Lumbosacral Angle after Spinal Cord Untethering in 23 Children with Tethered Cord Syndrome.

AIM: To analyze changes in the lumbosacral angle in children with tethered cord syndrome before and after spinal cord untethering surgery, and to determine the clinical value of such changes at the last follow-up. MATERIAL AND METHODS: We retrospectively analyzed 23 children over 5 years old who were treated with spinal cord untethering in our hospital from January 2010 to January 2021 and who had complete medical data. X-rays were used to examine the child's spine preoperatively, postoperatively, and at follow-up with frontal and lateral radiographs, and lumbosacral angle data were measured and analyzed. RESULTS: A total of 23 children aged 5-14 years had their lumbosacral angles measured and analyzed with a postoperative followup of 12-48 months. The mean preoperative lumbosacral angle was 70.30 ± 9.04°, the mean postoperative lumbosacral angle was 63.34 ± 5.60°, and the mean lumbosacral angle at the last follow-up was 61.61 ± 9.14°. There was a statistically significant reduction in the lumbosacral angle in the children postoperatively and at the last follow-up compared to the preoperative period (p=0.002; p=0.001). CONCLUSION: Spinal cord untethering can improve the inclination of the lumbosacral angle in children older than 5 years with tethered cord syndrome.

Comparison of the Curative Efficacy of Hemivertebra Resection via the Posterior Approach Assisted With Unilateral and Bilateral Internal Fixation in the Treatment of Congenital Scoliosis.

Objective: This study aimed to compare the curative efficacy of hemivertebra resection via the posterior approach assisted with unilateral and bilateral internal fixation in the treatment of congenital scoliosis (CS). Methods: In this study, 29 children (15 males and 14 females), who underwent hemivertebra resection via the posterior approach and received internal fixation from November 2005 to September 2018, were analyzed retrospectively. The age of these patients ranged from 0.9 to 15 years, with an average of 3.8 years. The follow-up duration ranged from 2 to 12.3 years, with an average of 5.7 years. The patients in group A received unilateral internal fixation, and those in group B received bilateral internal fixation. The operation duration, bleeding volume, and complications during the operation, as well as the Cobb angles of scoliosis and kyphosis before and after the operation and at the last follow-up, were compared between the two groups. Results: In group A, the operation duration was 207.4 ± 54.5 min, and the bleeding volume was 215.3 ± 75.4 ml; in group B, the operation duration was 249.5 ± 51.0 min, and the bleeding volume was 291.3 ± 115.6 ml (P < 0.05). The Cobb angles of segmental scoliosis, segmental kyphosis, cephalic compensatory curve, and caudal compensatory curve were significantly improved in the two groups after operation and at the last follow-up (P < 0.05). The post-operative correction rate of the scoliosis Cobb angle was 67.2% in group A and 79.5% in group B; and the difference was statistically significant (P < 0.05). At the last follow-up, the correction rate of the scoliosis Cobb angle was 72.7% in group A and 76.2% in group B (P > 0.05). After the operation and at the last follow-up, the correction rates of kyphosis were 83.1 and 79.6% in group A and 71.8 and 65.5% in group B (P > 0.05). Conclusion: Hemivertebra resection via posterior approach with unilateral internal fixation can also achieve the effect of bilateral internal fixation in the treatment of CS. It is able to preserve a certain degree of contralateral spinal growth potential and is a feasible method.

Glucocorticoid-induced expansion of classical monocytes contributes to bone loss.

Classical monocytes are commonly involved in the innate inflammatory response and are the progenitors of osteoclasts. Excess endogenous glucocorticoids (GCs) can increase the levels of classical monocytes in blood and bone marrow. The role of this cell population in high-dose exogenous GC-induced osteoporosis (GIOP) remains to be elucidated. In this study, GIOP was established in rats and mice by daily methylprednisolone injection, and monocyte subsets were analyzed by flow cytometry. We demonstrated that classical monocytes accumulate in bone marrow during GIOP. Similarly, the monocyte proportion among bone marrow nucleated cells was also increased in patients with steroid treatment history. We sorted classical monocytes and analyzed their transcriptional profile in response to GCs by RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that classical monocytes isolated from GC-treated rats exhibited osteoclast differentiation potential. Deletion of classical monocytes by clodronate liposome treatment prevented GIOP via inhibition of osteoclastogenesis and restoration of CD31HiendomucinHi vessels. Regarding the molecular mechanism, classical monocytes express high levels of glucocorticoid receptors. In vitro treatment with GCs increased both the percentage and absolute number of monocytes and promoted their proliferation. In summary, classical monocytes mediated GC-induced bone loss and are a potential target for therapeutic intervention in GIOP treatment.

Adaptive Bird-like Genome Miniaturization During the Evolution of Scallop Swimming Lifestyle.

Genome miniaturization drives key evolutionary innovations of adaptive traits in vertebrates, such as the flight evolution of birds. However, whether similar evolutionary processes exist in invertebrates remains poorly understood. Derived from the second-largest animal phylum, scallops are a special group of bivalve molluscs and acquire the evolutionary novelty of the swimming lifestyle, providing excellent models for investigating the coordinated genome and lifestyle evolution. Here, we show for the first time that genome sizes of scallops exhibit a generally negative correlation with locomotion activity. To elucidate the co-evolution of genome size and swimming lifestyle, we focus on the Asian moon scallop (Amusium pleuronectes) that possesses the smallest known scallop genome while being among scallops with the highest swimming activity. Whole-genome sequencing of A. pleuronectes reveals highly conserved chromosomal macrosynteny and microsynteny, suggestive of a highly contracted but not degenerated genome. Genome reduction of A. pleuronectes is facilitated by significant inactivation of transposable elements, leading to reduced gene length, elevated expression of genes involved in energy-producing pathways, and decreased copy numbers and expression levels of biomineralization-related genes. Similar evolutionary changes of relevant pathways are also observed for bird genome reduction with flight evolution. The striking mimicry of genome miniaturization underlying the evolution of bird flight and scallop swimming unveils the potentially common, pivotal role of genome size fluctuation in the evolution of novel lifestyles in the animal kingdom.

Posterior hemivertebra resection without internal fixation in the treatment of congenital scoliosis in very young children.

Objective: To retrospectively analyze the feasibility and efficacy of posterior hemivertebra resection without internal fixation in the treatment of congenital scoliosis in very young children. Methods: Sixteen cases of very young children with congenital scoliosis treated at our hospital from April 2000 to July 2019 were collected, including 8 cases of each sex, all of whom had type I/III congenital scoliosis and were operated on at a median (interquartile range) of 9.00 (7.75) months (range, 0.5-48 months) of age. All cases underwent posterior hemivertebra resection without internal fixation and wore orthopedic braces or plaster undershirts for more than six months after surgery, with a mean follow-up of 94.31 ± 65.63 months (range, 36-222 months). Results: Coronal plane: the preoperative Cobb angle for the segmental curve was 39.50 ± 9.70° compared to postoperative (19.19 ± 8.56°) and last follow-up (14.94 ± 12.11°) (both P < 0.01); the preoperative Cobb angle for the main curve was 34.19 ± 14.34° compared to postoperative (17.00 ± 11.70°) and last follow-up (17.56 ± 16.31°) (both P < 0.01); the preoperative Cobb angle of the proximal compensated curve was 14.88 ± 9.62° compared to postoperative (7.88 ± 4.66°) and last follow-up (8.38 ± 8.36°) (both P < 0.05); and the preoperative Cobb angle of the distal compensated curve was 13.50° (10.50°) (range, 4°-30°) compared with postoperative 4.50° (9.25°) (range, -3° to 25°) and final follow-up 5.50° (9.50°) (range, -3° to 33°) (both P < 0.01). Sagittal plane: the difference in the preoperative Cobb angle was 10.00° (14.00°) (range, -31° to 41°) for segmental kyphosis compared to postoperative 14.00° (24.50°) (range, -6° to 46°) and last follow-up 17.00° (22.55°) (range, -40° to 56°), and these were not statistically significant (both P > 0.05). There was a tendency for the thoracolumbar kyphosis to worsen and the lumbosacral kyphosis to improve during the follow-up period. Conclusion: Posterior hemivertebra resection without internal fixation is a feasible treatment for type I/III congenital scoliosis in very young children, but the correction of the sagittal deformity of the thoracolumbar spine is not satisfactory, and postoperative external fixation may require further improvement.

SEM study on filum terminale with tethered cord syndrome.

OBJECTIVE: To improve the understanding in pathology and provide steady proof for diagnosis and treatment of tethered cord syndrome (TCS), the ultrastructure of filum terminale (FT) with TCS will be researched, respectively. METHODS: Thirty-one fila were sectioned and divided into two groups according to diameter. Twenty-two fila thicker than 2 mm were placed into group 1; nine no thicker than 2 mm were placed into group 2. Their transverse and longitudinal sections were respectively submitted for scanning electron microscopy analysis. RESULTS: For the FTs with TCS, ultrastructural analysis confirmed the presence of abundant collagen bundles and adipocytes, sparse or invisible elastic and reticular fibers inside the FT, but the latter two fibers were still visible in the relative normal areas of FT; some abnormalities, such as thickening, distortion, adhesion or fusion to piece, relatively dense and disorderly arrangement at a different degree, were quite common for collagen fiber. Some areas looked blurry, and some crystallization appeared occasionally on their surface. For the FTs with TFTS, those changes as mentioned above were still exhibited, but slightly relatively. All the changes mentioned inside all the FTs may exist alone or concomitantly, rarely simultaneously. Moreover, they can be often seen focally or diffusely occasionally. CONCLUSIONS: Low elasticity resulting from the destruction of the three-dimensional structure of FT is involved in TCS. Early FT severing is a treatment of choice no matter whether its appearance looks normal.

Interference of circRNA HIPK3 alleviates cardiac dysfunction in lipopolysaccharide-induced mice models and apoptosis in H9C2 cardiomyocytes.

BACKGROUND: Circular RNAs (circRNAs) have been deemed to be microRNA (miRNA) sponges that are involved in multiple biological processes. It has not yet been corroborated whether the regulation of circular RNA HIPK3 (circHIPK3) can be used for the treatment of myocardial dysfunction. METHODS: In this study, we aimed to investigate the cardioprotective effects and apoptosis inhibition of circHIPK3 regulation on lipopolysaccharide (LPS)-induced myocarditis in vivo and vitro. C57BL/6 mice were exposed to LPS with or without knockdown of circHIPK3. Reverse transcription polymerase chain reaction (RT-PCR) testing was used to evaluate the expression of circHIPK3. Hematoxylin and eosin (HE) staining, immunohistochemistry (IHC), Cell Counting Kit-8 (CCK8), flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, enzyme-linked immunosorbent assay (ELISA), and western blotting were used to evaluate histopathology, proliferation, apoptosis, oxidative stress, and inflammatory response, respectively. Cardiac function and myocardial damage were also evaluated. RESULTS: It was proven that short hairpin RNA1 (shRNA1) was a superior interference of circHIPK3. The results revealed that knockdown of circHIPK3 effectively alleviated myocardial tissue damage, improved cardiac function, and suppressed cardiomyocyte apoptosis in the animal model of LPS-induced myocarditis. Furthermore, LPS-induced oxidative injuries and inflammation in the myocardium were also partly reversed after circHIPK3 knockdown. In vitro, being LPS-induced enhanced the levels of heart damage markers, simultaneously inhibited proliferation, promoted apoptosis, and stimulated oxidative stress and inflammation of H9C2 cells. Fortunately, the abnormalities mentioned were partly reversed following circHIPK3 knockdown. CONCLUSIONS: In this study, we characterized the expression and regulation of circHIPK3 in LPS-induced myocarditis in the animal model and H9c2 cells. The results demonstrated that circHIPK3 expression is significantly upregulated when exposed to LPS in vivo and in vitro. Knockdown of circHIPK3 effectively alleviated LPS-induced myocarditis.

Artesunate alleviates myocardial ischemia/reperfusion-induced myocardial necrosis in rats and hypoxia/reoxygenation-induced apoptosis in H9C2 cells via regulating the FAK/PI3K/Akt pathway.

BACKGROUND: The various anti-inflammatory, anti-apoptotic, and antioxidant effects of Artesunate (Art) have been explored in numerous studies. This study aimed to evaluate the function of Art on myocardial necrosis in apoptotic cardiomyocytes in vivo and in vitro. METHODS: Sprague Dawley (SD) rats were randomly divided into groups: a control group, a myocardial ischemia reperfusion (MI/R) group, and MI/R+ Art groups. To establish a MI/R model, rats were subjected to left anterior descending artery ischemia for 45 minutes, and then reperfusion for 2 hours. Hypoxia was induced in H9C2 cells by subjecting them to hypoxic conditions at 37 °C for 4 hours, before placing them in a normoxic chamber for 2 hours. The test methods were used in this test, such as echocardiography, enzyme-linked immunosorbent assay (ELISA), HE staining, TUNEL staining, immunohistochemistry, flow cytometry, western blot, and CCK-8 assay. RESULTS: Art improved myocardial systolic function caused by MI/R injury in vivo. Simultaneously, Art reduced the levels of cardiac troponin I (cTnl), creatine kinase-MB (CK-MB) and myohemoglobin (Mb) in vivo and in vitro. Moreover, Art inhibited cardiomyocyte apoptosis in vivo and in vitro. The focal adhesion kinase (FAK)/phosphatidylinositide-3 kinases (PI3K)/AKT signaling pathway was also activated by Art in vivo and in vitro. Furthermore, after inhibitor PF573228 was added, Art inhibited apoptosis in H9C2 cells via activation of the FAK/PI3K/AKT signaling pathway in vitro. CONCLUSIONS: This study confirms that Art alleviated MI/R injury and inhibited cardiomyocyte apoptosis in vivo and in vitro. Art exerted an inhibitory effect on cardiomyocyte apoptosis by activating the FAK/PI3K/AKT signaling pathway. Therefore, Art may serve as an alternative treatment for MI/R injury.