The brain protection of MLKL inhibitor necrosulfonamide against focal ischemia/reperfusion injury associating with blocking the nucleus and nuclear envelope translocation of MLKL and RIP3K.

Mixed lineage kinase like protein (MLKL) is a key mediator of necroptosis. While previous studies highlighted the important role of MLKL as one of the central regulators of brain damage against acute ischemic neuronal injury, how the activation of MLKL mediates brain injuries and cell death remains unclear, especially in astrocytes. In a transient middle cerebral artery occlusion (tMCAO) rat model in vivo, and an oxygen-glucose deprivation and reoxygenation (OGD/Re) injury model in both primary cultured astrocytes and human astrocytes, we show that necrosulfonamide (NSA), a MLKL specific inhibitor, reduces infarction volume and improves neurological deficits in tMCAO-treated rats. In addition, NSA treatment, as well as RIP1K inhibitor Nec-1 or RIP3K inhibitor GSK-872 treatment, decreases the OGD/Re-induced leakage of LDH in both primary cultured astrocytes and human astrocytes. NSA treatment also reduces the number of propidium iodide (PI)-positive cells, and prevents the upregulation of necroptotic biomarkers such as MLKL/p-MLKL, RIP3K/p-RIP3K, and RIP1K/p-RIP1K in ischemic penumbra of cerebral cortex in tMCAO-treated rats or in OGD/Re-treated human astrocytes. Importantly, NSA treatment blocks both the nucleus and nuclear envelope localization of MLKL/p-MLKL and RIP3K/p-RIP3K in ischemic cerebral cortex induced by tMCAO. Similarly, Co-immunoprecipitation assay shows that NSA treatment decreases tMCAO- or OGD/Re- induced increased combination of MLKL and RIP3K in nuclear envelope of ischemic penumbra of cerebral cortex or of primary cultured astrocytes, respectively. RIP3K inhibitor GSK-872 also reduces tMCAO-induced increased combination of MLKL and RIP3K in nuclear envelope of ischemic penumbra of cerebral cortex. These data suggest NSA exerts protective effects against focal ischemia/reperfusion injury via inhibiting astrocytic necroptosis through preventing the upregulation of necroptotic kinases as well as blocking both the nucleus and nuclear envelope co-localization of p-MLKL and p-RIP3K. The translocation of p-MLKL, along with p-RIP3K, to the nuclear envelope and the nucleus may play a crucial role in MLKL-mediated necroptosis under ischemic conditions.

DHA attenuates cartilage degeneration by mediating apoptosis and autophagy in human chondrocytes and rat models of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease that usually occurs in the elderly, and docosahexaenoic acid (DHA) plays a therapeutic role in cardiovascular disease, diabetes, and rheumatoid arthritis (RA) with its anti-inflammatory and antioxidant effects. The objective of this study is to investigate the effect and mechanism of DHA on hypertrophic differentiation and senescence of OA chondrocytes to provide a theoretical basis for the effect of OA clinical treatment. A human OA chondrocyte model was established by IL-1ß, and a rat model of OA was established by anterior cruciate ligament (ACL) transection and medial meniscectomy. The result showed DHA promoted chondrocyte proliferation and reduced apoptosis. Transmission electron microscopy (TEM) analysis showed that there were more autophagosomes in the cytoplasm under the treatment of DHA. Compared to the OA group, samples from the OA + DHA group showed thickened cartilage, reduced degeneration, and an increased rate of collagen II-positive cells, while the Mankin score was significantly lower. In addition, DHA decreased the expression of phosphorylated mammalian target of rapamycin (p-mTOR) and the ratio of light chain 3-I/II (LC3-I/II) and increased the expression of Beclin-1 and Bcl-2 measured by western blot analysis. Therefore, DHA promotes chondrocyte proliferation, reduces apoptosis, and increases autophagy in OA chondrocytes, a process that is accomplished by inhibiting the expression of mTOR, c-Jun N-terminal kinase (JNK), and p38 signaling pathways, providing new perspectives and bootstrap points for the prevention and treatment of OA.

Effects of Different Low-Temperature Storage Methods on the Quality and Processing Characteristics of Fresh Beef.

Low-temperature storage has become the most common way for fresh meat storage because of its lower cost and better preservation effect. Traditional low-temperature preservation includes frozen storage and refrigeration storage. The refrigeration storage has a good fresh-keeping effect, but the shelf life is short. Frozen storage has a long shelf life, but it has a great impact on the quality of meat structure and other qualities, and cannot achieve a complete "fresh-keeping" effect. With the development of food processing storage and freezing technology, two new storage methods, ice temperature storage and micro-frozen storage, have attracted more attention. In this paper, the effects of different low-temperature storage methods on the sensory, physicochemical properties, myofibrillar protein oxidation, microstructure, and processing characteristics of fresh beef were studied. The optimal storage methods under different storage requirements were analyzed to reveal the mechanism and efficacy of ice temperature storage and micro-frozen storage technology, as well as the advantages compared with traditional low-temperature refrigeration. It has practical significance for guiding the application of low-temperature storage of fresh meat. Finally, this study concluded that the longest shelf life could be achieved by frozen storage, and the best preservation effect was achieved during the shelf life of ice temperature storage, and the effect of micro-frozen storage on the myofibrillar protein oxidation and microstructure was the best.

Associations between obesity, diabetes mellitus, and cardiovascular disease with progression states of knee osteoarthritis (KOA).

BACKGROUND: Data on common comorbidities targeting at different progression states of knee osteoarthritis (KOA) in continuous time are limited. AIMS: To examine the associations between obesity, diabetes mellitus (DM), and cardiovascular disease (CVD) with the progression of KOA. METHODS: Data were obtained from the Osteoarthritis Initiative for up to 48 months. Progression states of KOA were defined as (1) normal; (2) asymptomatic radiographic KOA (RKOA, Kellgren-Lawrence grade ≥ 2 in at least one knee); (3) only knee symptoms; (4) symptomatic KOA (SxKOA, a combination of RKOA and knee symptoms in the same knee). A multi-state Markov model was used to investigate the associations while accounting for potential confounders. RESULTS: Participants with obesity had an increased risk of developing RKOA [normal to asymptomatic RKOA, adjusted hazard ratio (aHR) 1.55, 95% confidence interval (95% CI) (1.07, 2.24); only knee symptoms to SxKOA, aHR 2.25, 95% CI (1.60, 3.18)], and an increased risk of developing knee symptoms [normal to only knee symptoms, aHR 1.45, 95% CI (1.15, 1.83); asymptomatic RKOA to SxKOA, aHR 1.33, 95% CI (1.16, 1.52)]. DM was also significantly associated with development of RKOA or knee symptoms [normal to asymptomatic RKOA, aHR 1.92, 95% CI (1.12, 3.30); normal to only knee symptoms, aHR 1.78, 95% CI (1.12, 2.84)]. Knee symptoms were less likely to be relieved among participants with CVD, compared with those without [only knee symptoms to normal, aHR 0.60, 95% CI (0.38, 0.94)]. CONCLUSIONS: Obesity, DM and CVD are associated with an increased risk for SxKOA progression. Common comorbidities should be considered to prevent KOA development.

Tendon Stem/Progenitor Cell-Laden Nanofiber Hydrogel Enhanced Functional Repair of Patellar Tendon.

Functional repair of tendons remains a challenge to be overcome for both clinicians and scientists. We have previously reported a three-dimensional RADA peptide hydrogel that provides a suitable microenvironment for human tendon stem/progenitor cells (TSPCs) survival and tenogenesis. In this study, we explore the potential of in vivo patellar tendon repair by human TSPC-laden RADA hydrogel in rats, which were sacrificed at 4 and 8 weeks after operation. Hind limb function test, macroscopical and histological examination, tendon cell amount and alignment analysis, and radiographic assessments were performed at several time points. Our results demonstrated that human TSPC-laden RADA hydrogel (RADA+TSPC group) boosted in vivo patellar tendon repair with better ambulatory function recovery compared with the control groups, in which tendon defects were untreated (Defect group) or treated with RADA hydrogel alone (RADA group). In addition, better macroscopic appearance and improved matrix organization in the repaired tendon with less cell amount and reduced adipocyte accumulation and blood vessel formation were observed in the RADA+TSPC group. Moreover, tendon defect treated with TSPC-laden RADA hydrogel resulted in diminished heterotopic ossification (HO) at 8 weeks postoperation, which was indicated by both X-ray examination and micro-computed tomography scan. Taken together, the combination of TSPC and nanofiber hydrogel provide an optimistic alternative method to accelerate functional tendon repair with reduced HO. Impact statement Our study clearly demonstrates the combination of tendon stem/progenitor cell and nanofiber hydrogel provide a new and optimistic tissue engineering strategy to treat tendon injury by accelerating functional tendon repair with reduced heterotopic ossification. The clinical translation is also very promising, which can provide a minimally invasive, nonsurgical, or complementary treatment methods to treat human tendon injury.

Fluoride-immobilized co-processing and resource utilization of aluminum-electrolyzed spent cathode carbon in brick-fired kiln.

Spent cathode carbon (SCC) is hazardous waste from the electrolytic aluminum industry due to its high levels of soluble fluoride, while brick-fired kiln provides the clay and heating conditions needed to immobilize fluoride. However, SCC reusing is still understudied, meanwhile co-processing and resource utilization of SCC in brick-fired kiln were still not reported in the literatures in addition to a Chinese patent of the authors. Here, the effects of firing temperatures, firing time, clay doses and calcium doses on the fluoride-immobilized performance of SCC co-processing were explored in a simulated brick-firing kiln, and their mechanisms were analyzed by SEM and XRD. The results indicated that clay-added co-processing in brick-fired kiln was a preferred choice without required additional additives or operations. The leached fluoride met Chinese standards by clay-added co-processing at ≥ 800 °C/ ≥ 40 g clay/ ≥ 120 min. Clay and calcium-added co-processing in brick-fired kiln was another alternative choice with higher fluoride-immobilization rates. The leached fluoride met Chinese standard (GB5085.3-2007) by clay and calcium-added co-processing at ≥ 500 °C/ ≥ 30 min/ ≥ 5 g clay/ ≥ 0.5 g CaCO3. SEM and XRD indicated that SiO2 in clay reacted with sodium in SCC and formed vitreous analog (Na1.55Al1.55Si0.45O4) to prevent fluoride ion migration and the newly-formed k-Feldspar (K2O.Al2O3.6SiO2) may adsorb fluoride ions in clay-added co-processing. Soluble fluoride NaF in SCC were converted into water-insoluble cuspidine in clay and calcium-added co-processing, in addition to the crystalline phase conversion in clay-added co-processing. Therefore, the risks of finished bricks to human health and the environment were greatly reduced after clay-added or clay and calcium-added treatments.

Effects of Perioperative Fascia Iliaca Compartment Block on Postoperative Pain and Hip Function in Elderly Patients With Hip Fracture.

Purpose: Pain management is a challenging issue in elderly patients with hip fracture. Despite the accepted clinical outcomes following hip surgery, pain and prolonged recovery time are the most difficult consequences associated with the rehabilitation process. The purpose of this study was to evaluate pain relief and functional improvement associated with the Fascia Iliaca Compartment Block (FICB) during the perioperative period of elderly patients with hip fracture. Patients and methods: This study included 120 elderly patients with hip fracture, who were admitted to our institution between January 2019 and December 2020. The participants were subsequently randomly divided into the routine analgesia (RA) and fascia iliaca compartment block (FICB) groups. Inter-group differences were compared via VAS scores at rest and during movement, Harris hip scores (HHS), presence of complications, adverse events after surgery, and length of hospital stay. Results: The FICB group VAS scores at rest at 6 hour, 1 and 3 days, and 1 week after surgery were significantly lower than the RA group (P < .05). Moreover, the FICB group VAS scores with movement were markedly lower at 6 hour, 1 and 3 days, as well as 1 and 2 weeks after surgery (P < .05). The HHS of the FICB and RA groups were (53.41±8.63) and (40.02±9.61), respectively, on the seventh day after surgery, and the difference was statistically significant (P < .05). The incidence of postoperative complications and adverse events in the FICB group were not statistically different from the RA group. The average hospital stay of the FICB group was 2.12 days shorter than the RA group, but the difference did not reach statistical significance (P = .13). Conclusion: FICB provides superior analgesic effect both at rest and with movement, along with rapid short-term recovery of hip function following surgery in elderly patients with hip fracture, without increasing postoperative complications or adverse events.

Incidence of hip fracture among middle-aged and older Chinese from 2013 to 2015: results from a nationally representative study.

China is experiencing remarkable changes in people aging and migration. Therefore, the incidence and associated factors for hip fracture might differ from previous results. A nationally representative study of hip fracture enables policymakers to formulate preventive strategies and provide information on resource allocation. PURPOSE: To estimate the incidence of hip fracture, between 2013 and 2015, among the middle-aged and older Chinese population. METHODS: Individuals with hip fractures between 2013 and 2015 were identified from the China Health and Retirement Longitudinal Study. The sex-specific incidence and the associated factors of hip fracture were assessed. RESULTS: Among 19,112 individuals (51.4% women; mean age 60.5 years) included in the analysis, 408 (2.13%) had a hip fracture between 2013 and 2015. Moreover, the annual incidence of hip fracture for men and women were 1065 and 1069 per 100,000, respectively. The incidence of hip fracture increased with age (p < 0.001). A history of chronic disease, being unmarried, and individuals without insurance were associated with a higher incidence of hip fracture. Interestingly, the incidence of hip fracture was higher among individuals with fewer years of education (p = 0.002). The North-East regions of China had the lowest incidence of hip fracture (1022 per 100,000) between 2013 and 2015, followed by the North (1602 per 100,000), South-Central (2055 per 100,000), East (2173 per 100,000), and South-West (2537 per 100,000) regions. Finally, the incidence was highest among participants living in the North-West region (3244 per 100,000). CONCLUSION: Between 2013 and 2015, the incidence of hip fracture is high among the middle-aged and older Chinese population. Furthermore, it varied significantly according to sociodemographic and geographic factors. Therefore, the support of targeted health policies and cost-effective preventive strategies are warranted in China.

Low deacetylation degree chitosan oligosaccharide protects against IL-1ß induced inflammation and enhances autophagy activity in human chondrocytes.

Osteoarthritis (OA) is a degenerative joint disease, which can lead to joint pain, stiffness, deformity and dysfunction, that seriously affects the quality of life in patients. At present, the treatments of OA mainly include early pharmacological treatment and late joint replacement. However, current pharmacological treatment has limited efficacy and undesired side effects. Chitosan oligosaccharide (COS) is a kind of nontoxic and biodegradable oligo-saccharide, which is composed of 2-20 glucosamine or N-acetylglucosamine linked by ß-1,4 glycosidic bond. Studies have shown that COS has significant biological properties like antimicrobial, anti-inflammatory, antioxidant, and anti-tumor, as well as immunoregulation ability. However, the effects of COS on OA have not been clarified. In this study, we explored the protective effects of COS with different degrees of deacetylation on chondrocytes stimulated by interleukin 1ß (IL-1ß) in vitro. The results showed that IL-1ß inhibited cell proliferation and promoted cell apoptosis. Besides that, IL-1ß increased the expression of the major chondro-degrading genes MMP13 and ADAMTS-5, while decreased the expression of COL2A and ACAN. COS with different degrees of deacetylation (HDACOS, MDACOS, LDACOS) had different effects on IL-1ß induced inflammation. LDACOS had the most obvious anti-inflammatory effects to inhibit the expression of MMP13 and ADAMTS-5 while promoted the expression of COL2A and ACAN. In addition, we found that the expression of autophagy-related gene Beclin-1 was up-regulated, and the ratio of LC3-II/LC3-I was increased in the LDACOS group. Furthermore, transmission electron microscopy (TEM) analysis showed that the number of intracellular autophagosomes increased significantly with the treatment of LDACOS. Based on our research, we suggested that LDACOS could inhibit chondrocytes inflammation and promote cell autophagy, and might be a protective drug for the treatment of OA.

Peculiar Steric Hindrance Assists Monoclinic Phase Formation toward High-Quality All-Inorganic Perovskites.

Bromine-containing metal halide all-inorganic perovskite CsPbI2Br exhibits excellent photoelectric performance and supreme thermal and structural stabilities; it is thus attractive for use as photoabsorbing layers in perovskite solar cells (PSCs). However, when steric hindrance molecules are introduced, the complicated phase transition mechanism and the difficult-to-control crystallization process in CsPbI2Br are not well understood. Here, we introduce a class of sterically hindered cesium naphthenate small molecules to control the crystallization process of CsPbI2Br films. Of interest, a new intermediate monoclinic phase has been discovered which leads to formation of dense and nonporous polycrystalline perovskite films. This phenomenon was also explained by density functional theory. The residues of steric hindrance molecules inside the CsPbI2Br film also improve its stability. We further show that as the ring number of cycloalkanes increases, the hindrance for the crystallization becomes more significant. Thus, by choosing the suitable steric hindrance, the optimal photovoltaic efficiency is 15.45%.

High-efficiency production of 5-aminovalerate in engineered Escherichia coli controlled by an anaerobically-induced nirB promoter.

Biobased production of 5-aminovalerate (5AVA) from biomass can support a sustainable and economic biorefinery process to produce bio-based nylon 5 for food packaging materials. Cost-competitive production of 5AVA from biomass is a key factor in the successful commercialization of nylon 5. Bioproduction of 5AVA is a promising candidate for the industrial process to the current petrochemical route. In this study, we developed an artificial 2-keto-6-aminocaproate-mediated pathway for cost-competitive and high efficiency production of 5AVA in engineered Escherichia coli. Firstly, the combination of native l-lysine α-oxidase (RaiP) from Scomber japonicas, α-ketoacid decarboxylase (KivD) from Lactococcus lactis and aldehyde dehydrogenase (PadA) from Escherichia coli could efficiently convert l-lysine into 5AVA. Moreover, the engineered strains ML03-PnirB-RKP, ML03-PPL-PR-RKP, ML03-PM1-93-RKP induced by anaerobic condition, temperature-induced, constitutive expression instead of expensive isopropyl ß-D-thiogalactoside were constructed, respectively. The use of nirB promoter induced by anaerobic condition not only could attain a higher titer of 5AVA than PL-PR and M1-93 promoters, but omit cost of expensive exogenous inducers. After the replacement of industrial materials, 5AVA titer successfully reached 33.68 g/L in engineered strain ML03-PnirB-RKP via biotransformation. This biotransformation process conduces to the cosmically industrial 5AVA bioproduction.

The protective effects of granulocyte-macrophage colony-stimulating factor against radiation-induced lung injury.

BACKGROUND: Radiation-induced lung injury (RILI) is a common complication of thoracic cancer radiation therapy. Currently, there is no effective treatment for RILI. RILI is associated with chronic inflammation, this injury is perpetuated by the stimulation of chemokines and proinflammatory cytokines. Recent studies have demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a pivotal role in inflammation and fibrosis. This study aimed to investigate the protective effect of GM-CSF against the development of RILI in lung tissue. METHOD: First, a single fraction of radiation at a dose of 16 Gy was targeted at the entire thorax of wild-type (WT) C57BL/6 mice and GM-CSF-/- mice to induce RILI. Second, we detected the radioprotective effects of GM-CSF by measuring the inflammatory biomarkers and fibrosis alteration on radiated lung tissues. Furthermore, we investigated the potential mechanism of GM-CSF protective effects in RILI. RESULTS: The GM-CSF-/- mice sustained more severe RILI than the WT mice. RILI was significantly alleviated by GM-CSF treatment. Intraperitoneally administered GM-CSF significantly inhibited inflammatory cytokine production and decreased epithelial-mesenchymal transition (EMT) in the RILI mouse model. CONCLUSIONS: GM-CSF was shown to be an important modulator of RILI through regulating inflammatory cytokines, which provides a new strategy for the prevention and treatment of RILI.

Stability Designs of Cell Membrane Cloaked Magnetic Carbon Nanotubes for Improved Life Span in Screening Drug Leads.

Convenient strategies to provide natural cell membranes (CMs)-camouflaged nanomaterials with enhanced stability would prompt the advancement of CMs-coated biomimetic technology and expand the application of these emerging nanomaterials. Herein, we have developed stability-enhanced CMs-camouflaged magnetic carbon nanotubes (MCNTs) to screen drug leads from traditional Chinese medicine (TCMs) that target membrane receptors. By modifying MCNTs with N-ethyl-N'-(3-(dimethylamino)propyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), the resulting covalent immobilized CMs-camouflaged MCNTs have improved stability, where the losing amount (20 mg g-1) was significantly decreased compared with that of the unimmobilized materials (40 mg g-1). The high expression ephrinb2/HEK293 cell lines were used to camouflage the EDC/NHS modified MCNTs (CMCNTs) to endow it with drug-screening sites. Moreover, with inherited properties from CMs, ephrinb2/HEK293 CMs-camouflaged CMCNTs possessed good binding capacity and selectivity, and three potential drug leads as mesaconine, deltaline, and 13-dehydroxyindine were screened from Aconitum carmichaeli Debx. The pharmacological assays indicated that mesaconine and 13-dehydroxyindine could inhibit cancer cell growth by targeting ephrinb2. As a result, this surface engineering method not only offers an insight into fabrication of stabilized CMs-coated nanomaterials but also inspires more brilliant work in the future and paves the way for the biomimetic functional modification of CNTs for a variety of applications.

Fluffy honeycomb-like activated carbon from popcorn with high surface area and well-developed porosity for ultra-high efficiency adsorption of organic dyes.

Fluffy honeycomb-like activated carbon with ultra-high surface area and well-developed hierarchical porous structure is simply prepared from popcorn by NaOH activation as adsorbent for dye removal. The popcorn has an unique fluffy structure, which originates from the corn via a rapid puffing process and is reserved during the following carbonization and NaOH activation. The ultra-high surface area and developed hierarchical porous structure make PDAC-4 show an outstanding adsorption capacity of 7765 mg·g-1 for Rhodamine B (2500 mg·L-1), which is several times higher than those of the adsorbents ever reported. Moreover, PDAC-4 also has excellent adsorption performance for other dyes, such as Congo Red, Methylene Blue and Methyl Orange. The superior adsorption performance of PDACs to organic dyes opens its potential application in the purification of dye wastewater.

17ß-estradiol rescues damages following traumatic brain injury from molecule to behavior in mice.

Traumatic brain injury (TBI) is a public health concern, and causes cognitive dysfunction, emotional disorders, and neurodegeration, as well. The currently available treatments are all symptom-oriented with unsatifying efficacy. It is highly demanded to understand its underlying mechanisms. Controlled cortical impact (CCI) was used to induce TBI in aged female mice subjected to ovariectomy. Brain damages were assessed with neurological severity score, brain infarction and edema. Morris water maze and elevated plus maze were applied to evaluate the levels of anxiety. Apoptosis in the hippocampus was assayed with Fluoro-Jade B staining and TUNEL staining. Western blot was employed to measure the expression of NMDA receptor subunits and phosphorylation of ERK1/2, and biochemical assays were used to estimate oxidative stress. 17beta-Estradiol (E2) was intraperitoneally administered at 10-80 µg/kg once per day for 7 consecutive days before or after CCI. Chronic administration of E2 both before and immediately after CCI conferred neuroprotection, reducing neurological severity score, brain infarction, and edema in TBI mice. Additionally, E2 improved many aspects of deleterious effects of TBI on the hippocampus, including neuronal apoptosis, dysfunction in spatial memory, reduction in NR2B, enhancement of oxidative stress, and activation of ERK1/2 pathway. The present study provides clue for the notion that E2 has therapeutic potential for both prevention and intervention of TBI-induced brain damages.

Cerebral hemorrhage therapy by targeting VEGF and HGF in a preclinical trial in rats.

Cerebral hemorrhage is the most common type of human cerebrovascular disease and frequently causes paralysis, vegetative state and mortality. The modulatory actions of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are vital in the human nervous system. The present study investigated the association between cerebral hemorrhage and the expression of VEGF and HGF in a rat model of cerebral hemorrhage. The therapeutic potential of cerebral hemorrhage was also evaluated using targeted drugs for VEGF and HGF in the cerebral hemorrhage rat model. Behavioral and preclinical changes and the survival rates of rats were assessed after treatment with VEGF receptor (VEGFR) and HGF receptor (HGFR). The results of Tarlov scores demonstrated that movement of limbs and coordination when walking were significantly improved in moderate and severe hemorrhage lesions in the VEGFR plus HGFR­treated group and mainly alleviated in primary hemorrhage lesions compared with rats in the single VEGFR or HGFR­treated groups and the control group (**P<0.01). Decreasing expression levels of VEGF and HGF were observed in the neural tissue of animals treated with VEGFR plus HGFR compared with the control group (**P<0.01). These preclinical observations indicated that VEGF and HGF serve a function in the pathological injury and repair of cerebral tissue in rats with cerebral hemorrhages. The therapeutic benefits of VEGFR plus HGFR suggested that VEGFR plus HGFR may be candidate drugs for cerebral hemorrhage, and thus offer a promising treatment for clinicians and doctors.