Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

Involvement of Siglec-15 in regulating RAP1/RAC signaling in cytoskeletal remodeling in osteoclasts mediated by macrophage colony-stimulating factor

DNAX-associated protein 12 kD size(DAP12)is a dominant immunoreceptor tyrosine-based activation motif(ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis.Although several DAP12-associated receptors(DARs)have been identified in osteoclasts,including triggering receptor expressed on myeloid cells 2(TREM-2),C-type lectin member 5 A(CLEC5A),and sialic acid-binding Ig-like lectin(Siglec)-15,their precise role in the development of osteoclasts and bone remodeling remain poorly understood.In this study,mice deficient in Trem-2,Clec5a,Siglec-15 were generated.

Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions:an intravascular ultrasound study

OBJECTIVES To investigate whether negative remodeling(NR) detected by intravascular ultrasound(IVUS) of the side branch ostium(SBO) would affect in-stent neointimal hyperplasia(NIH) at the one-year follow-up and the clinical outcome of target lesion failure(TLF) at the long-term follow-up for patients with left main bifurcation(LMb) lesions treated with a two-stent strategy.METHODS A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention(PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre-and post-PCI and at the 1-year follow-up were enrolled in phase Ⅰ analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index(RI) for predicting NIH ≥ 50% was analyzed next. The phase Ⅱ analysis focused on the incidence of TLF as the primary endpoint at the 1-to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI.RESULTS In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic(ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893(0.778, 1.000), P = 0.002. In phase Ⅱ: the TLR rate(35.8% vs. 5.3%, P < 0.0001)was significantly higher in the several NR(s NR, defined as RI ≤ 0.85) group than in the non-s NR group.CONCLUSION The NR of LCx O is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy,and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process.METHODS A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay.RESULTS Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fcgroup.CONCLUSIONS In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.

Effects of Yerba Mate Consumption (Ilex paraguariensis) on Cardiac Remodeling in Rats

This study investigated the effects of yerba mate consumption, a South American beverage, on cardiac remodeling in rats. For this purpose, 24 male Wistar rats were divided into Control Group (CG) which received filtered water and a standard diet, and Yerba Mate Group (YM), 6 g of Ilex paraguariensis in 100 ml water and the same diet, for 30 days. The YM group showed a reduction in final body weight and food consumption without altering weight gain. Regarding cardiac remodeling, the YM group exhibited a decrease in the right ventricle weight/final body weight ratio, suggesting cardiac atrophy, without affecting the atria and left ventricle. There was no change in cardiomyocyte area or nuclear fractal dimension in both groups. However, animals that consumed yerba mate showed increased collagen deposition and a smaller fractal dimension in the left ventricle. The consumption of yerba mate at room temperature for 30 days induced changes in cardiac remodeling, as evidenced by increased collagen deposition and alterations in fractal dimension in the left ventricle.

Global gene expression profiling of perirenal brown adipose tissue whitening in goat kids reveals novel genes linked to adipose remodeling

Background Brown adipose tissue(BAT)is known to be capable of non-shivering thermogenesis under cold stimulation,which is related to the mortality of animals.In the previous study,we observed that goat BAT is mainly located around the kidney at birth,and changes to white adipose tissue(WAT)in the perirenal adipose tissue of goats within one month after birth.However,the regulatory factors underlying this change is remain unclear.In this study,we systematically studied the perirenal adipose tissue of goat kids in histological,cytological,and accompanying molecular level changes from 0 to 28 d after birth.Results Our study found a higher mortality rate in winter-born goat kids,with goat birthing data statistics.Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d.This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids.Additionally,we found a series of changes of BAT during the first 28 d after birth,such as whitening,larger lipid droplets,decreased mitochondrial numbers,and down-regulation of key thermogenesis-related genes(UCP1,DIO2,UCP2,CIDEA,PPARGC1a,C/EBPb,and C/EBPa).Then,we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats.Furthermore,12 candidate genes were found to potentially regulate goat BAT thermogenesis.The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.While apoptosis may play a limited role,it is largely not critical in this transition process.Conclusions We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids,with notable species differences in the expression of adipose tissue marker genes,and we highlighted some potential marker genes for goat BAT and WAT.Additionally,the change from BAT to WAT does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.

Evidence-Based Complementary and Alternative Medicine Effects of Capybara Oil on Cardiac Remodeling of C57bl/6 Mice

Cardiovascular diseases are the main cause of morbidity and mortality in the world, and obesity and the metabolic syndrome are risk factors for its development. One of the therapies to reduce cardiovascular risk is the use of polyunsaturated fatty acids. In Brazil, a source of such acid is the oil extracted from the fat of the capybara. The objective of this work is to study the effects of the capybara oil on lipid and glucose metabolism, as well as its effects on the adipose tissue and cardiac remodeling. We assessed the effects of capybara oil treatment on body mass, lipid and carbohydrate metabolism, systolic blood pressure, adipose tissue and cardiac remodeling, and performed an ultrastructural evaluation of the myocardium in C57Bl/6 mice treated with high-fat diet. Treatment with capybara oil reduced total cholesterol and triglyceride levels, systolic blood pressure, visceral and subcutaneous adipose tissue, and adipocyte diameter. In addition, cardiac remodeling was attenuated, preserving cardiomyocytes, increasing vascularization, reducing cardiomyocyte hypertrophy and the extracellular matrix, and preserving the morphological integrity of mitochondria. Capybara oil has several beneficial effects on the cardiovascular and metabolic system, and further studies are needed to better understand its role in the prevention or treatment of cardiovascular diseases.

Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

Change in self-image pressure level before and after autologous fat breast augmentation and its effect on social adaptability

BACKGROUND There is an increasingly strong demand for appearance and physical beauty in social life,marriage,and other aspects with the development of society and the improvement of material living standards.An increasing number of people have improved their appearance and physical shape through aesthetic plastic surgery.The female breast plays a significant role in physical beauty,and droopy or atrophied breasts can frequently lead to psychological inferiority and lack of confidence in women.This,in turn,can affect their mental health and quality of life.AIM To analyze preoperative and postoperative self-image pressure-level changes of autologous fat breast augmentation patients and their impact on social adaptability.METHODS We selected 160 patients who underwent autologous fat breast augmentation at the First Affiliated Hospital of Xinxiang Medical University from January 2020 to December 2022 using random sampling method.The general information,selfimage pressure level,and social adaptability of the patients were investigated using a basic information survey,body image self-assessment scale,and social adaptability scale.The self-image pressure-level changes and their effects on the social adaptability of patients before and after autologous fat breast augmentation were analyzed.RESULTS We collected 142 valid questionnaires.The single-factor analysis results showed no statistically significant difference in the self-image pressure level and social adaptability score of patients with different ages,marital status,and monthly income.However,there were significant differences in social adaptability among patients with different education levels and employment statuses.The correlation analysis results revealed a significant correlation between the self-image pressure level and social adaptability score before and after surgery.Multiple factors analysis results showed that the degree of concern caused by appearance in selfimage pressure,the degree of possible behavioral intervention,the related distress caused by body image,and the influence of body image on social life influenced the social adaptability of autologous fat breast augmentation patients.CONCLUSION The self-image pressure on autologous fat breast augmentation patients is inversely proportional to their social adaptability.

Rapid correction of chronic hyperglycemia and bone remodeling,warning against overdoing

It is widely recognized that chronic hyperglycemia decreases bone quality,although little is known about the impact of the rapid correction of chronic hyperglycemia on the quality of bone remodeling.This spotlight article explores this correlation by focusing on the stages of bone remodeling linked to glucose levels.

Carotid versus axillary artery cannulation for descending aorta remodeling in type A acute aortic dissection

BACKGROUND Arterial cannulation sites for the surgical repair of type A aortic dissection(AAD)have evolved from right axillary artery(AA)cannulation to bilateral carotid artery(CA)based of femoral artery(FA)cannulation.Postoperative descending aorta remodeling is closely linked to the false lumen area ratio(FLAR),defined as false lumen area/aortic area,as well as to the incidence of renal replacement therapy(RRT).AIM To investigate the effect of the updated arterial cannulation strategy on descending aortic remodeling.METHODS A total of 443 AAD patients who received FA combined cannulation between March 2015 and March 2023 were included in the study.Of these,209 received right AA cannulation and 234 received bilateral CA cannulation.The primary outcome was the change in FLAR,as calculated from computed tomography angiography in three segments of the descending aorta:Thoracic(S1),upper abdominal(S2),and lower abdominal(S3).Secondary outcomes were the incidence of RRT and the serum inflammation response,as observed by the levels of high sensitivity C reaction protein(hs-CRP)and Interleukin-6(IL-6).RESULTS The postoperative/preoperative ratio of FLAR in S2 and S3 was higher in the AA group compared to the CA group(S2:0.80±0.08 vs 0.75±0.07,P<0.001;S3:0.57±0.12 vs 0.50±0.12,P<0.001,respectively).The AA group also had a significantly higher incidence of RRT(19.1%vs 8.5%,P=0.001;odds ratio:2.533,95%CI:1.427-4.493)and higher levels of inflammation cytokines 24 h after the procedure[hr-CRP:117±17 vs 104±15 mg/L;IL-6:129(103,166)vs 83(69,101)pg/mL;both P<0.001]compared to the CA group.CONCLUSION The CA cannulation strategy was associated with better abdominal aorta remodeling after AAD repair compared to AA cannulation,as observed by a greater change in FLAR and lower incidence of RRT.

Discussion on the Status Quo of Vocational College Students’Self-Image and its Improvement Strategies

An individual’s self-image is a multi-dimensional and multi-structural concept.Its internal dimensions include ability,knowledge,values,personality,and temperament,and its external dimensions are physical appearance,behavior,and clothing.A good image will have a positive impact both in life and at work.We will choose appropriate clothing and makeup to modify the external image and cultivate positive qualities such as correct values and an optimistic attitude towards life to enhance internal dimensions.Among them,“personality”and“ability”mostly belong to the research category of mental health education,and“values”fit in the research field of ideological and political education.Ideological and political education and mental health education are both important components of higher education,which show similarities between them.Ideological and political education and mental health education can complement each other in many ways to enhance students’self-image.

Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

Cardiac remodeling and physical training post myocardial infarction

After myocardial infarction(MI), the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. There is growing clinical consensus that exercise training may beneficially alter the course of post-MI myocardial remodeling and improve cardiac function. This review summarizes the present state of knowledge regarding the effect of post-MI exercise training on infarcted hearts. Due to the degree of difficulty to study a viable human heart at both protein and molecular levels, most of the detailed studies have been performed by using animal models. Although there are some negative reports indicating that post-MI exercise may further cause deterioration of the wounded hearts, a growing body of research from both human and animal experiments demonstrates that post-MI exercise may beneficially alter the course of wound healing and improve cardiac function. Furthermore, the improved function is likely due to exercise training-induced mitigation of reninangiotensin-aldosterone system, improved balance between matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, favorable myosin heavy chain isoform switch, diminished oxidative stress, enhanced antioxidant capacity, improved mitochondrial calcium handling, and boosted myocardial angiogenesis. Additionally, meta-analyses revealed that exercise-based cardiac rehabilitation has proven to be effective, and remains one of the least expensive therapies for both the prevention and treatment of cardiovascular disease, and prevents re-infarction.

The role of microRNAs in bone remodeling

Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that micro RNAs（mi RNAs）, known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression,and growing numbers of novel mi RNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis,and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of mi RNAs in regulating bone remodeling as well as novel applications for mi RNAs in biomaterials for therapeutic purposes.

Adipose tissue lipolysis and remodeling during the transition period of dairy cows

Elevated concentrations of plasma fatty acids in transition dairy cows are significantly associated with increased disease susceptibility and poor lactation performance. The main source of plasma fatty acids throughout the transition period is lipolysis from adipose tissue depots. During this time, plasma fatty acids serve as a source of calories mitigating the negative energy balance prompted by copious milk synthesis and limited dry matter intake.Past research has demonstrated that lipolysis in the adipose organ is a complex process that includes not only the activation of lipolytic pathways in response to neural, hormonal, or paracrine stimuli, but also important changes in the structure and cellular distribution of the tissue in a process known as adipose tissue remodeling. This process involves an inflammatory response with immune cell migration, proliferation of the cellular components of the stromal vascular fraction, and changes in the extracellular matrix. This review summarizes current knowledge on lipolysis in dairy cattle, expands on the new field of adipose tissue remodeling, and discusses how these biological processes affect transition cow health and productivity.

Stem cell mechanisms during left ventricular remodeling post-myocardial infarction:Repair and regeneration

Post-myocardial infarction(MI),the left ventricle(LV)undergoes a series of events collectively referred to as remodeling.As a result,damaged myocardium is replaced with fibrotic tissue consequently leading to contractile dysfunction and ultimately heart failure.LV remodeling post-MI includes inflammatory,fibrotic,and neovascularization responses that involve regulated cell recruitment and function.Stem cells(SCs)have been transplanted post-MI for treatment of LV remodeling and shown to improve LV function by reduction in scar tissue formation in humans and animal models of MI.The promising results obtained from the application of SCs post-MI have sparked a massive effort to identify the optimal SC for regeneration of cardiomyocytes and the paradigm for clinical applications.Although SC transplantations are generally associated with new tissue formation,SCs also secrete cytokines,chemokines and growth factors that robustly regulate cell behavior in a paracrine fashion during the remodeling process.In this review,the different types of SCs used for cardiomyogenesis,markers of differentiation,paracrine factor secretion,and strategies for cell recruitment and delivery are addressed.

Revisiting tumor angiogenesis:vessel co-option,vessel remodeling,and cancer cell-derived vasculature formation

Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen,nutrients,and other essential factors.The well-known vascular endothelial growth factor(VEGF) signaling is crucial for sprouting angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature,which has become therapeutic targets in clinical practice.However,the survival benefits gained from targeting VEGF signaling have been very limited,with the inevitable development of treatment resistance.In this article,we discuss the most recent findings and understanding on how solid tumors evade VEGF-targeted therapy,with a special focus on vessel co-option,vessel remodeling,and tumor cell-derived vasculature establishment.Vessel co-option may occur in tumors independently of sprouting angiogenesis,and sprouting angiogenesis is not always required for tumor growth.The differences between vessel-like structure and tubule-like structure formed by tumor cells are also introduced.The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.

Expression and role of specificity protein 1 in the sclera remodeling of experimental myopia in guinea pigs

AIM：To study the expression of collagen I and transcription factor specificity protein 1（Sp1）,a transforming growth factor-β1（TGF-β1） downstream target,and reveal the impact of the TGF-β1-Sp1 signaling pathway on collagen remodeling in myopic sclera.METHODS：Seventy-five 1-week-old guinea pigs were randomly divided into normal control,form deprivation myopia（FDM）,and self-control groups.FDM was induced for different times using coverage with translucent latex balloons and FDM recovery was performed for 1wk after 4wk treatment;then,changes in refractive power and axial length were measured.Immunohistochemistry and reverse transcription-polymerase chain reaction were used to evaluate dynamic changes in collagen I and Sp1 expression in the sclera of guinea pigs with emmetropia and experimental myopia,and the relationship between collagen I and Sp1 levels was analyzed.RESULTS：In the FDM group,the refractive power was gradually changed（from 2.09±0.30 D at week 0 to-1.23±0.69 D,-4.17±0.59 D,-7.07±0.56 D,and-4.30±0.58 D at weeks 2,4,6,and 1wk after 4wk,respectively;P〈0.05）,indicating deepening of myopia.The axial length was increased（from 5.92±0.39 mm at week 0 to 6.62±0.36 mm,7.30±0.34 mm,7.99±0.32 mm,and 7.41±0.36 mm at weeks 2,4,6,and 1wk after 4wk;P〈0.05）.The m RNA and protein expression of Sp1 and collagen I in the sclera of the FDM group was lower than that of the control groups（P〈0.05）,and the reduction was eye-coverage time-dependent.Furthermore,correlation between Sp1 and collagen I down-regulation in the myopic sclera was observed.CONCLUSION：Our data indicate that transcription factor Sp1 may be involved in the regulation of type I collagensynthesis/degradation during myopic sclera remodeling,suggesting that TGF-β1 signaling plays a role in the development and progression of myopia.