Background: Current medical management of endometriosis leads to suppression of ovulation and will not be helpful for women with endometriosis who are desirous of pregnancy. Thus, drugs that can both treat endometriosis and its associated infertility are highly warranted. Objective: Anti-angiogenic agents are potential drugs for patients with endometriosis and infertility. Among these drugs, dopamine agonist (DA) is promising since it does not interfere with ovulation, is safe, and not teratogenic. The aim of the study is to determine the efficacy and safety of DA for improving reproductive outcomes in women with endometriosis and infertility. Methods: A qualitative narrative review was done from inception to July 31, 2022 using the appropriate MeSH terms in PubMed, Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and World Health Organization International Clinical Trials Registry Platform. Date analysis was through qualitative analysis and synthesis of researches and their outcome measures. Results: No studies used the core outcomes for trials evaluating treatments for infertility associated with endometriosis. All the included articles in the review supported the possible anti-angiogenic effects of DA on the vascular endothelial growth factor [VEGF] /VEGF receptor system. The use of DA does not have an effect on ovulation and menstrual cyclicity. Studies on safety profile of DA were consistent with existing data. Conclusion Most of studies reviewed demonstrated that DA were effective in reducing endometriotic lesions. However, further research is required to establish whether this anti-angiogenic effect can improve reproductive outcomes in women with endometriosis-associated infertility.
Endometriosis ; Dopamine Agonists ; Infertility ; Angiogenesis Inducing Agents ; Angiogenesis Inhibitors

Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.
Animals ; Mice ; Interleukin-10 ; Bifidobacterium breve ; Up-Regulation ; Angiogenesis Inhibitors ; Sunitinib ; X-Ray Microtomography ; Administration, Oral ; Wound Healing ; Antibodies, Neutralizing

Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.
Humans ; Female ; Medicine, Chinese Traditional ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Angiogenesis ; Angiogenesis Inhibitors/therapeutic use* ; Ovarian Neoplasms/genetics* ; Neovascularization, Pathologic/genetics*

The present study investigated the mechanism of components in stasis-resolving and collateral-dredging Chinese herbal medicines, including scutellarin(Scu), paeonol(Pae), and hydroxy safflower yellow A(HSYA), in the treatment of psoriasis by regulating angiogenesis and inflammation. The human umbilical vein endothelial cells(HUVECs) cultured in vitro were divided into a normal group, a model group, a VEGFR tyrosine kinase inhibitor Ⅱ(VRI) group, and Scu, Pae, and HSYA groups with low, me-dium, and high doses. Cell viability was detected by the CCK-8 assay. Cell migration was detected by wound healing assay. Tube formation assay was used to measure the tube formation ability. Western blot was used to detect the protein expression of the VEGFR2/Akt/ERK1/2 signaling pathway. The secretion levels of inflammatory cytokines IFN-γ, IL-1β, IL-6, and TNF-α were detected by ELISA. The results showed that compared with the model group, all the Scu, Pae, and HSYA groups could reduce cell viability, inhibit cell migration and tube formation(P<0.05, P<0.01), and down-regulated the protein expression of VEGFR2, p-VEGFR2, Akt, p-Akt, ERK1/2, and p-ERK1/2. Scu and Pae could down-regulate VEGFR2 expression(P<0.05, P<0.01), while other groups only showed a downward trend. Scu and Pae significantly reduced IFN-γ and IL-6 levels(P<0.01), and HSYA significantly reduced the levels of IFN-γ, IL-1β, and IL-6(P<0.01). Scu, Pae, and HSYA had no significant effect on TNF-α. The results suggested that Scu, Pae, and HSYA may exert a therapeutic role in psoriasis-related angiogenesis and inflammation by inhibiting VEGFR2/Akt/ERK1/2 signaling pathway and inhibiting the secretion of IFN-γ, IL-1β, and IL-6.
Angiogenesis Inhibitors/pharmacology* ; China ; Human Umbilical Vein Endothelial Cells ; Humans ; Neovascularization, Pathologic/drug therapy* ; Vascular Endothelial Growth Factor A/metabolism*

Lung cancer is a highly vascular tumors, over the past ten years, anti-angiogenes is has been proved to be an effective and highly promising combinational treatment. The data of the combination of anti-angiogenesis with chemotherapy, targeted therapy, immunotherapy has been constantly updating. Advanced lung cancer patients, no matter different groups or different stages of the disease, are benefited from anti-angiogenes. In this paper, based on the clinical status and unsolved problems, combined with the latest clinical and translational research data, we reviewed the current anti-angiogenesis treatment of lung cancer.
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Angiogenesis Inhibitors/therapeutic use* ; Humans ; Immunotherapy ; Lung Neoplasms/pathology* ; Molecular Targeted Therapy ; Neovascularization, Pathologic/drug therapy*

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism for cerebral radiation necrosis (CRN) development. Antiangiogenic agents (Bevacizumab) alleviates brain edema symptoms caused by CRN through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that Bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' performance status and brain necrosis imaging. Considering that the efficacy of antiangiogenic therapy is mainly related to the duration of drug action, low-dose antiangiogenic agents can achieve favorable efficacy. Prevention is the best treatment. The occurrence of CRN is associated with tumor-related factors and treatment-related factors. By controlling these factors, CRN can be effectively prevented.
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Angiogenesis Inhibitors/pharmacology* ; Bevacizumab/therapeutic use* ; Brain/metabolism* ; Consensus ; Humans ; Lung Neoplasms/drug therapy* ; Necrosis/etiology* ; Radiation Injuries/etiology* ; Vascular Endothelial Growth Factor A/metabolism*

OBJECTIVE: To observe the effect of electroacupuncture (EA) on vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3), proinflammatory factors and apoptosis in myocardial tissue in mice with acute myocardial ischemia (AMI), and to explore the mechanism of EA for AMI. METHODS: Fifty male C57BL/6 mice were randomly divided into a sham operation group, a model group, an EA group, an inhibitor group and an inhibitor+EA group, 10 mice in each group. Except for the sham operation group, the mice in the remaining groups were intervented with ligation at the left anterior descending (LAD) coronary artery to establish AMI model. The mice in the sham operation group were intervented without ligation after thoracotomy. The mice in the EA group were intervented with EA at "Shenmen" (HT 7) and "Tongli" (HT 5), disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity, 30 min each time, once a day, for 3 d. The mice in the inhibitor group were treated with intraperitoneal injection of SAR 131675 (12.5 mg•kg^-1•d^-1, once a day for 3 d). The mice in the inhibitor+EA group were injected intraperitoneally with SAR 131675 30 min before EA. The ECG before modeling, 30 min after modeling and 3 d after intervention was detected, and the ST segment displacement was recorded; after the intervention, the ELISA method was applied to measure the contents of serum creatine kinase isoenzyme (CK-MB), aspartate aminotransferase (AST) as well as tumor necrosis factor-α (TNF-α) and interleukin-23 (IL-23) in myocardial tissue; the HE staining method was used to observe the morphological changes of myocardial tissue; the immunofluorescence double labeling method was applied to measure the number of co-expression positive cells of VEGF-C/VEGFR-3 in myocardial tissue; the TUNEL method was used to detect the level of cardiomyocyte apoptosis; the Western blot method was applied to measure the protein expressions of VEGF-C, VEGFR-3, b-lymphoma-2 (Bcl-2), activated caspase-3 (Cleaved Caspase-3) and activated poly adenosine diphosphate ribose polymerase-1 (Cleaved PARP-1). RESULTS: Compared with the sham operation group, in the model group the ST segment displacement was increased (P<0.01); the contents of CK-MB, AST, TNF-α and IL-23 were increased (P<0.01); the arrangement of myocardial fibers was disordered, and interstitial inflammatory cell infiltration was obvious; the number of co-expression positive cells of VEGF-C/VEGFR-3 was decreased (P<0.01); the number of cardiomyocyte apoptosis was increased (P<0.01); the expressions of VEGF-C, VEGFR-3 and Bcl-2 were decreased (P<0.01); the expressions of Cleaved Caspase-3 and Cleaved PARP-1 were increased (P<0.01). Compared with the model group, in the EA group the ST segment displacement was decreased (P<0.01); the contents of CK-MB, AST, TNF-α, IL-23 were decreased (P<0.01); the severity of myocardial pathological injury was reduced; the number of co-expression positive cells of VEGF-C/VEGFR-3 was increased (P<0.01); the number of cardiomyocyte apoptosis was reduced (P<0.01); the expressions of VEGF-C, VEGFR-3 and Bcl-2 were increased (P<0.01); the expressions of Cleaved Caspase-3 and Cleaved PARP-1 were reduced (P<0.01). There was no significant difference in all the indexes between the model group and the inhibitor group (P>0.05). Compared with the model group, the protein expression of VEGF-C was increased in the inhibitor+EA group (P<0.01). Compared with the inhibitor group, in the EA group the ST segment displacement was decreased (P<0.01); the contents of CK-MB, AST, TNF-α, IL-23 were decreased (P<0.01); the severity of myocardial pathological injury was reduced; the number of co-expression positive cells of VEGF-C/VEGFR-3 was increased (P<0.05); the number of cardiomyocyte apoptosis was reduced (P<0.01); the expressions of VEGF-C, VEGFR-3 and Bcl-2 were increased (P<0.01); the expressions of Cleaved Caspase-3 and Cleaved PARP-1 were reduced (P<0.01). Compared with the inhibitor+EA group, all the indexes in the EA group were improved except the protein expression of VEGF-C (P<0.01). CONCLUSION EA could relieve the inflammatory reaction and apoptosis in AMI mice, and its mechanism may be related to activating VEGF-C/VEGFR-3 pathway and promoting lymphangion genesis.
Mice ; Male ; Animals ; Electroacupuncture ; Vascular Endothelial Growth Factor Receptor-3 ; Caspase 3 ; Vascular Endothelial Growth Factor C ; Tumor Necrosis Factor-alpha/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Poly(ADP-ribose) Polymerase Inhibitors ; Mice, Inbred C57BL ; Myocardial Ischemia/metabolism* ; Apoptosis ; Interleukin-23 ; Proto-Oncogene Proteins c-bcl-2

Lnc-HUR1 is an HBV-related long non-coding RNA, which can promote the proliferation of hepatoma cells and the occurrence and development of liver cancer. In this study we explored the effect of lnc-HUR1 on the apoptosis of hepatocellular carcinoma cells by taking the approach of immunoblotting, quantitative real time PCR, luciferase reporter assay, chromatin immunoprecipitation (ChIP) and flow cytometry. We found that overexpression of lnc-HUR1 significantly reduced the activity of caspase3/7 and the cleavage of PARP-1, while knocking down of lnc-HUR1 significantly increased the activity of caspase3/7 and promoted the cleavage of PARP-1 in HepG2 cells treated with TGF-β, pentafluorouracil or staurosporine. Consistently, the data from Annexin-V/PI staining showed that overexpression of lnc-HUR1 inhibited apoptosis, while knockdown of lnc-HUR1 promoted apoptosis. Moreover, overexpression of lnc-HUR1 up-regulated the apoptosis inhibitor Bcl-2 and down-regulated the pro-apoptotic factor BAX at both RNA and protein levels. In the CCL4-induced acute liver injury mice model, the expression of Bcl-2 in the liver tissue of lnc-HUR1 transgenic mice was higher than that of the control mice. The data from ChIP assay indicated that lnc-HUR1 reduced the enrichment of p53 on Bcl-2 and BAX promoters. All these results indicated that lnc-HUR1 inhibited the apoptosis by promoting the expression of apoptosis inhibitor Bcl-2 and inhibiting the expression of apoptosis promoting factor BAX. Further studies showed that lnc-HUR1 regulated the transcription of Bcl-2 and BAX in HCT116 cells, but had no effect on the expression of Bcl-2 and BAX in HCT116 p53^-/- cells, indicating that lnc-HUR1 regulates the transcription of Bcl-2 and BAX dependent upon the activity of p53. In conclusion, HBV upregulated lnc-HUR1 can inhibit the apoptosis of hepatoma cells. Lnc-HUR1 inhibits apoptosis by inhibiting the transcriptional activity of p53. These results suggest that lnc-HUR1 plays an important role in the occurrence and development of HBV-related hepatocellular carcinoma.
Animals ; Annexins/pharmacology* ; Apoptosis ; Carcinoma, Hepatocellular/genetics* ; Cell Proliferation ; Hep G2 Cells ; Hepatitis B virus/metabolism* ; Humans ; Liver Neoplasms/genetics* ; Mice ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/pharmacology* ; RNA, Long Noncoding/metabolism* ; Staurosporine/pharmacology* ; Transforming Growth Factor beta/pharmacology* ; Tumor Suppressor Protein p53/pharmacology* ; bcl-2-Associated X Protein/pharmacology*

OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.
Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; Angiogenesis Inhibitors/therapeutic use* ; Endothelial Growth Factors/therapeutic use* ; Hemorrhage ; Hypertension, Pregnancy-Induced ; Oxygen/therapeutic use* ; Retinopathy of Prematurity/drug therapy* ; Retrospective Studies ; Risk Factors ; Vascular Endothelial Growth Factor A

Lung cancer is one of the leading causes of cancer-related morbidity and mortality. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) have become the standard treatment for EGFR-mutated advanced non-small cell lung cancer (NSCLC). Unfortunately, drug resistance is inevitable in most cases. EGFR-TKI combined with angiogenesis inhibitors is a treatment scheme being explored to delay the therapeutic resistance, which is called "A+T treatment". Several clinical trials have demonstrated that the A+T treatment can improve the progression free survival (PFS) of the NSCLC patients. However, compared to EGFR-TKI monotherapy, the benefits of the A+T treatment based on different EGFR-TKIs, as well as its safety and exploration prospects are still unclear. Therefore, we reviewed the literature related to all three generations EGFR-TKIs combined with angiogenesis inhibitors, and summarized the mechanism, benefit, safety, optimal target population of A+T treatment.
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Angiogenesis Inhibitors/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*