Source-Guided Target Feature Reconstruction for Cross-Domain Classification and Detection.

Existing cross-domain classification and detection methods usually apply a consistency constraint between the target sample and its self-augmentation for unsupervised learning without considering the essential source knowledge. In this paper, we propose a Source-guided Target Feature Reconstruction (STFR) module for cross-domain visual tasks, which applies source visual words to reconstruct the target features. Since the reconstructed target features contain the source knowledge, they can be treated as a bridge to connect the source and target domains. Therefore, using them for consistency learning can enhance the target representation and reduce the domain bias. Technically, source visual words are selected and updated according to the source feature distribution, and applied to reconstruct the given target feature via a weighted combination strategy. After that, consistency constraints are built between the reconstructed and original target features for domain alignment. Furthermore, STFR is connected with the optimal transportation algorithm theoretically, which explains the rationality of the proposed module. Extensive experiments on nine benchmarks and two cross-domain visual tasks prove the effectiveness of the proposed STFR module, e.g., 1) cross-domain image classification: obtaining average accuracy of 91.0%, 73.9%, and 87.4% on Office-31, Office-Home, and VisDA-2017, respectively; 2) cross-domain object detection: obtaining mAP of 44.50% on Cityscapes → Foggy Cityscapes, AP on car of 78.10% on Cityscapes → KITTI, MR -2 of 8.63%, 12.27%, 22.10%, and 40.58% on COCOPersons → Caltech, CityPersons → Caltech, COCOPersons → CityPersons, and Caltech → CityPersons, respectively.

Normobaric hyperoxia alleviates complement C3-mediated synaptic pruning and brain injury after intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease, and the complement cascade exacerbates brain injury after ICH. As the most abundant component of the complement system, complement component 3 (C3) plays essential roles in all three complement pathways. However, the effects of C3 on neurological impairment and brain injury in ICH patients and the related mechanism have not been fully elucidated. Normobaric hyperoxia (NBO) is regarded as a treatment for ICH patients, and recent clinical studies also have confirmed the neuroprotective role of NBO against acute ICH-mediated brain damage, but the underlying mechanism still remains elusive. AIMS: In the present study, we investigated the effects of complement C3 on NBO-treated ICH patients and model mice, and the underlying mechanism of NBO therapy in ICH-mediated brain injury. RESULTS: Hemorrhagic injury resulted in the high plasma C3 levels in ICH patients, and the plasma C3 levels were closely related to hemorrhagic severity and clinical outcomes after ICH. BO treatment alleviated neurologic impairments and rescued the hemorrhagic-induced increase in plasma C3 levels in ICH patients and model mice. Moreover, the results indicated that NBO exerted its protective effects of on brain injury after ICH by downregulating the expression of C3 in microglia and alleviating microglia-mediated synaptic pruning. CONCLUSIONS: Our results revealed that NBO exerts its neuroprotective effects by reducing C3-mediated synaptic pruning, which suggested that NBO therapy could be used for the clinical treatment of ICH.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

BACKGROUND: Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. AIM: To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. METHODS: A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. RESULTS: Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). CONCLUSION: In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Normobaric hyperoxia therapy in acute ischemic stroke: A literature review.

Background: Ischemic stroke is one of the most severe cerebrovascular diseases that leads to disability and death and seriously endangers health and quality of life. Insufficient oxygen supply is a critical factor leading to ischemic brain injury. However, effective therapies for ischemic stroke are lacking. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve prognosis after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBHO) has been shown to have neuroprotective effects during ischemic stroke and is considered an appropriate neuroprotective therapy for ischemic stroke. Evidence indicates that NBHO plays a neuroprotective role through different mechanisms in acute ischemic stroke. Recent studies have also reported that combinations with other drug therapies can enhance the efficacy of NBHO in ischemic stroke. Here, we aimed to provide a summary of the potential mechanisms underlying the use of NBHO in ischemic stroke and an overview of the benefits of NBHO in ischemic stroke. Methods: We screened 83 articles on PubMed and other websites. A quick review was conducted, including clinical trials, animal trials, and reviews of studies in the field of NBHO treatment published before July 1, 2023. The results were described and synthesized, and the bias risk and evidence quality of all included studies were assessed. Results: The results were divided into four categories: the mechanism of NBHO, animal and clinical trials of NBHO, the clinical application and prospects of NBHO, and adverse reactions of NBHO. Conclusion: NBHO is a simple, non-invasive therapy that may be delivered early after stroke onset, with promising potential for the treatment of acute ischemic stroke. However, the optimal therapeutic regimen remains uncertain. Further studies are needed to confirm its efficacy and safety.

Free peroneal artery perforator flap for reconstruction of traumatic limb soft tissue defects: A retrospective case series study.

BACKGROUND: The free peroneal artery perforator (FPAP) flap is used for soft tissue defects after burns and trauma. However, the use of FPAP flaps to repair limb soft tissue defects for immediate reconstruction was rarely reported previously. Therefore, the purpose of this report is to evaluate free peroneal artery perforator flap to reconstruct traumatic limb soft tissue defects for immediate reconstruction. PATIENTS AND METHODS: A total of 25 cases of limb soft tissue defects undergoing immediate reconstruction of FPAP flap transfer were retrospectively evaluated from January 2019 to June 2019 in our institute. The locations of defects included the palm (10 cases), finger (5 cases), foot (7 cases), ankle (2 cases) and wrist (1 case). The sizes of defect varied from 3 × 2 cm to 15 × 7 cm (54.1 cm2 in average). Flaps were harvested based on the peroneal perforator vessels, initially marked using hand-held Doppler. RESULTS: Average size of harvested flap was 9.7 × 6.2 cm (ranging from 3.5 × 2 cm to 16 × 8 cm). All perforators were harvested from the peroneal artery and the arterial diameter ranged from 0.8 to 1.7 mm. The average pedicle length was 3.04 cm (range, 1.85-4.75 cm). Five vascular thrombosis were found including three cases of arterial thrombosis and two cases of venous thrombosis which were successfully salvaged by re-operation and vein graft. Satisfying functional outcome and acceptable appearance were achieved at 6 months or longer after surgery (range, 6-15 months, 12 months in average). All flaps survived at the end-point. CONCLUSIONS: The FPAP flap is a reliable and thin fasciocutaneous flap, which can be used for repairing limb soft tissue defects. The FPAP flap can be used for covering defects with various appearances, locations, and sizes.

Effect of ferroptosis on chronic cerebral hypoperfusion in vascular dementia.

Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer's disease and is caused by impaired nerve cell function resulting from cerebrovascular disease and vascular risk factors. Chronic cerebral hypoperfusion (CCH) is a common pathological and physiological state that may result from cerebral ischemia and hypoxia, causing widespread diffuse lesions in the brain parenchyma which leads to progressive nerve damage. Transferrin (TF) and transferrin receptor 1 (TfR1), two proteins involved in iron uptake, were upregulated by CCH, whereas ferroprotein (FPN), a protein involved in iron efflux, was downregulated. This process may involve various mechanisms including tau and iron regulatory proteins (IRP). CCH can also exacerbate lipid peroxidation caused by an iron imbalance by inhibiting glutathione peroxidase 4 (Gpx4) synthesis and some Gpx4 independent pathways through cystine/glutamate transporters (system Xc-), ultimately leading to ferroptosis in nerve cells and accelerating the progression of VaD.

The protective effects of EGCG was associated with HO-1 active and microglia pyroptosis inhibition in experimental intracerebral hemorrhage.

Intracerebral hemorrhage (ICH), which has high mortality and disability rate is associated with microglial pyroptosis and neuroinflammation, and the effective treatment methods are limited Epigallocatechin-3-gallate (EGCG) has been found to play a cytoprotective role by regulating the anti-inflammatory response to pyroptosis in other systemic diseases. However, the role of EGCG in microglial pyroptosis and neuroinflammation after ICH remains unclear. In this study, we investigated the effects of EGCG pretreatment on neuroinflammation-mediated neuronal pyroptosis and the underlying neuroprotective mechanisms in experimental ICH. EGCG pretreatment was found to remarkably improved neurobehavioral performance, and decreased the hematoma volume and cerebral edema in mice. We found that EGCG pretreatment attenuated the release of hemin-induced inflammatory cytokines (IL-1ß, IL-18, and TNF-α). EGCG significantly upregulated the expression of heme oxygenase-1 (HO-1), and downregulated the levels of pyroptotic molecules and inflammatory cytokines including Caspase-1, GSDMD, NLRP3, mature IL-1ß, and IL-18. EGCG pretreatment also decreased the number of Caspase-1-positive microglia and GSDMD along with NLRP3-positive microglia after ICH. Conversely, an HO-1-specific inhibitor (ZnPP), significantly inhibited the anti-pyroptosis and anti-neuroinflammation effects of EGCG. Therefore, EGCG pretreatment alleviated microglial pyroptosis and neuroinflammation, at least in part through the Caspase-1/GSDMD/NLRP3 pathway by upregulating HO-1 expression after ICH. In addition, EGCG pretreatment promoted the polarization of microglia from the M1 phenotype to M2 phenotype after ICH. The results suggest that EGCG is a potential agent to attenuate neuroinflammation via its anti-pyroptosis effect after ICH.

Development and validation of a mutation-annotated prognostic score for intrahepatic cholangiocarcinoma after resection: a retrospective cohort study.

BACKGROUND: The value of existing prognostic models for intrahepatic cholangiocarcinoma is limited. The inclusion of prognostic gene mutations would enhance the predictive efficacy. METHODS: In the screening cohorts, univariable Cox regression analysis was applied to investigate the effect of individual mutant genes on overall survival (OS). In the training set, multivariable analysis was performed to evaluate the independent prognostic roles of the clinicopathological and mutational parameters, and a prognostic model was constructed. Internal and external validations were conducted to evaluate the performance of this model. RESULTS: Among the recurrent mutations, only TP53 and KRASG12 were significantly associated with OS across all three screening cohorts. In the training cohort, TP53 and KRASG12 mutations in combination with seven other clinical parameters (tumor size, tumor number, vascular invasion, lymph node metastasis, adjacent invasion, CA19-9, and CEA), were independent prognostic factors for OS. A mutation-annotated prognostic score (MAPS) was established based on the nine prognosticators. The C-indices of MAPS (0.782 and 0.731 in the internal and external validation cohorts, respectively) were statistically higher than those of other existing models ( P <0.05). Furthermore, the MAPS model also demonstrated significant value in predicting the possible benefits of upfront surgery and adjuvant therapy. CONCLUSIONS: The MAPS model demonstrated good performance in predicting the OS of intrahepatic cholangiocarcinoma patients. It may also help predict the possible benefits of upfront surgery and adjuvant therapy.

Friend or foe: role of pathological tau in neuronal death.

Neuronal death is one of the most common pathological hallmarks of diverse neurological diseases, which manifest varying degrees of cognitive or motor dysfunction. Neuronal death can be classified into multiple forms with complicated and unique regulatory signaling pathways. Tau is a key microtubule-associated protein that is predominantly expressed in neurons to stabilize microtubules under physiological conditions. In contrast, pathological tau always detaches from microtubules and is implicated in a series of neurological disorders that are characterized by irreversible neuronal death, such as necrosis, apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy-dependent neuronal death and phagocytosis by microglia. However, recent studies have also revealed that pathological tau can facilitate neuron escape from acute apoptosis, delay necroptosis through its action on granulovacuolar degeneration bodies (GVBs), and facilitate iron export from neurons to block ferroptosis. In this review, we briefly describe the current understanding of how pathological tau exerts dual effects on neuronal death by acting as a double-edged sword in different neurological diseases. We propose that elucidating the mechanism by which pathological tau affects neuronal death is critical for exploring novel and precise therapeutic strategies for neurological disorders.

[Short-term impact of COVID-19 on semen parameters: A retrospective study].

OBJECTIVE: To observe the changes in semen parameters after COVID-19 infection and clarify its impact on male fertility. METHODS: We collected semen samples from 82 male patients infected with COVID-19 in the past 2 months (the infection group) and 14 normal healthy men (the control group), obtained their semen parameters and compared them between the two groups before and after COVID-19 infection. RESULTS: There were no statistically significant differences in the baseline semen parameters between the infection and control groups (P > 0.05), nor in the semen volume within the infection group before and after infection (P > 0.05). Compared with the normal controls, the patients showed significantly decreased sperm concentration, total sperm count, percentage of progressively motile sperm, sperm motility and percentage of morphologically normal sperm after COVID-19 infection (P < 0.05), which were reduced even more significantly in those with than in those without fever during infection (P < 0.05). No statistically significant difference was observed in the semen quality of the patients with normal body temperature before and after COVID-19 infection (P > 0.05). Spearman correlation analysis showed no significant correlation between semen parameters and the severity of fever during infection (P > 0.05). CONCLUSION: COVID-19 infection decreases the semen quality of the patient, and fever during infection is a significant influencing factor. The severity of fever, however, is not related to the reduction of semen quality.

Correlation between plasma glutathione peroxidase 4 and N-acetylneuraminic acid levels with clinical risk stratification and prognosis of patients with acute coronary syndrome.

OBJECTIVES: To investigate the correlation between plasma glutathione peroxidase 4 (GPX4) and N-acetyl-neuraminic acid (Neu5Ac) with clinical risk stratification and outcomes of acute coronary syndrome (ACS) patients. METHODS: Between October 2018 and July 2019, 413 patients that were scheduled for coronary angiography were enrolled in this prospective study at the First Affiliated Hospital of Bengbu Medical College, Bengbu, China. Patients were divided into control and ACS groups. Patients with ACS were divided into 3 risk levels based on their thrombolysis in myocardial infarction risk score. After discharge, ACS patients were followed for the incidence of major adverse cardiac events (MACEs). For the analysis of cumulative endpoint event occurrences, the Kaplan-Meier method was applied. RESULTS: The ACS group had lower plasma GPX4 but higher Neu5Ac levels than the control group. There was a greater increase in plasma Neu5Ac in the high-risk group when compared with the medium-risk and low-risk groups, while GPX4 levels were higher in the low-risk group. The MACEs group had higher plasma Neu5Ac but lower GPX4 levels than the non-MACEs group. The plasma Neu5Ac was an independent risk factor but GPX4 was a protective factor for MACEs. CONCLUSION: Glutathione peroxidase 4 and Neu5Ac levels in plasma can be used to diagnose, stratify risks, and predict long-term outcomes in patients with ACS.

A rat study model of depression-driven chronic prostatitis by modulating the PI3K/Akt/mTOR network.

Depression and chronic prostatitis (CP) are two common diseases that affect the human population worldwide. Clinically, it has been demonstrated that andrological patients often simultaneously suffer from depression and CP. Prior investigations have established that depression acts as an independent risk factor for CP. Herein, we explored the correlation between depression and CP using bioinformatics tools and through animal experiments. The potential targets and signalling pathways involved in depression and CP were predicted using bioinformatics tool, while depression in the rat model was established through chronic restraint stress. The expression of the related proteins and mRNA was assessed by Western blotting and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Relative to those in the control rats, the protein contents of PI3K, p-Akt, and p-mTOR were lower in the model rats (p < 0.05). Similarly, the transcript levels of PI3K, Akt, and mTOR was also relatively lower in the model rats (p < 0.05). And PI3K/Akt agonists reduced inflammation in rat prostate tissue, accompanied by significant increases in the transcript and protein expression levels of PI3K, Akt, and mTOR. Thus, we proposed that depression model rats may induce CP as a result of mediation by the negative regulation of the PI3K/Akt/mTOR signalling network.

Altered intra- and inter-network brain functional connectivity in upper-limb amputees revealed through independent component analysis.

Although cerebral neuroplasticity following amputation has been observed, little is understood about how network-level functional reorganization occurs in the brain following upper-limb amputation. The objective of this study was to analyze alterations in brain network functional connectivity (FC) in upper-limb amputees (ULAs). This observational study included 40 ULAs and 40 healthy control subjects; all participants underwent resting-state functional magnetic resonance imaging. Changes in intra- and inter-network FC in ULAs were quantified using independent component analysis and brain network FC analysis. We also analyzed the correlation between FC and clinical manifestations, such as pain. We identified 11 independent components using independent component analysis from all subjects. In ULAs, intra-network FC was decreased in the left precuneus (precuneus gyrus) within the dorsal attention network and left precentral (precentral gyrus) within the auditory network; but increased in the left Parietal_Inf (inferior parietal, but supramarginal and angular gyri) within the ventral sensorimotor network, right Cerebelum_Crus2 (crus II of cerebellum) and left Temporal_Mid (middle temporal gyrus) within the ventral attention network, and left Rolandic_Oper (rolandic operculum) within the auditory network. ULAs also showed decreased inter-network FCs between the dorsal sensorimotor network and ventral sensorimotor network, the dorsal sensorimotor network and right frontoparietal network, and the dorsal sensorimotor network and dorsal attention network. Correlation analyses revealed negative correlations between inter-network FC changes and residual limb pain and phantom limb pain scores, but positive correlations between inter-network FC changes and daily activity hours of stump limb. These results show that post-amputation plasticity in ULAs is not restricted to local remapping; rather, it also occurs at a network level across several cortical regions. This observation provides additional insights into the plasticity of brain networks after upper-limb amputation, and could contribute to identification of the mechanisms underlying post-amputation pain.

The alleviative effect of flavonol-type Nrf2 activator rhamnazin from Physalis alkekengi L. var. franchetii (Mast.) Makino on pulmonary disorders.

Rhamnazin (RN) is a flavonol isolated from the calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino, which has been used for treating pulmonary diseases in traditional Chinese medicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a therapeutic target for pulmonary diseases. In the present study, the underlying mechanism and pharmacological effect of RN against pulmonary disorders are investigated. Human lung epithelial Beas-2B cell and RAW 264.7 murine macrophage-based cell models, and a cigarette smoke (CS)-induced pulmonary impairment mice model are adopted for investigation in vitro and in vivo. RN is identified to be an Nrf2 activator, which promotes Nrf2 dissociation from Keap1 via reacting with the Cys151 cysteine residue of Keap1, and suppresses Nrf2 ubiquitination. In addition, RN is able to attenuate toxicant-stimulated oxidative stress and inflammatory response in vitro. Importantly, RN significantly relieves CS-induced oxidative insult and inflammation, and RN-induced inhibition of inflammation is related to inhibition of nuclear transcription factor-κB (NF-κB) and induction of cell autophagy. In conclusion, our data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF-κB activation and promoting autophagy. RN is a promising candidate for the therapy of pulmonary disorders.

Mechanism by which Huoxue Tongluo Qiwei Decoction improves the erectile function of rats with diabetic erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. RATIONALE: To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. MATERIALS AND METHODS: The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. CONCLUSION: Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCß signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

Explore the effects of pulmonary fibrosis on sperm quality and the role of the PI3K/Akt pathway based on rat model.

Researches were reported that respiratory diseases can lead to male infertility; however, it is unclear whether there is a relationship between pulmonary fibrosis (PF) and male infertility. This study examined the influence of PF on sperm quality and its mechanisms. The key signalling pathway of male infertility caused by PF was predicted based on bioinformatics research. After modelling, we evaluated semen quality. Real-time quantitative polymerase chain reaction and Western blotting were used to measure the protein and mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylation-protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl2) in rat testicular cells. Compared with group A (48.77 ± 4.67; 59.77 ± 4.79), the sperm concentration and total sperm viability of group B (8.44 ± 1.71; 15.39 ± 3.48) showed a downward trend (p < 0.05). Western blotting showed that the protein expressions of PI3K, p-Akt and Bcl2 in the testes of group B (0.30 ± 0.06; 0.27 ± 0.05; 0.15 ± 0.03) was significantly lower than those of group A (0.71 ± 0.07; 0.72 ± 0.06; 0.50 ± 0.06) (p < 0.05). The hypoxic environment induced by PF can inhibit the expression of PI3K, p-Akt and Bcl2 protein and eventually cause dysfunctional spermatogenesis.

A Bioinformatic Investigation of the Mechanism Underlying Migraine-Induced Erectile Dysfunction.

BACKGROUND: Over recent years, an increasing body of literature has focused on the relationship between erectile dysfunction (ED) and migraine. However, the specific mechanism is unclear. MATERIALS AND METHODS: We used a bioinformatic database to predict the targets and pathways associated with migraine and ED. Twenty male SD rats were randomly divided into a blank group (Group A, n = 10) and a migraine model group (Group B, n = 10). The rats in Group A were subcutaneously injected with normal saline (2 ml/kg) into the back of the neck. Rats in Group B were subcutaneously injected with nitroglycerin 10 mg/kg (5 mg/ml) into the back of the neck in order to create an animal model of migraine. Next, we carried out the measurement of erectile function. We used hematoxylin and eosin (HE) to compare the tissue structure of the cavernous body of the penis. Western blotting was used to determine the expression levels of PI3K, p-AKT, and p-mTOR in the protein; Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) was used to determine the expression levels of PI3K, AKT, and mTOR in the messenger ribonucleic acid (mRNA). RESULTS: There are 117 intersection targets of migraine and ED, involving 188 cell biological processes (BP), 21 cellular components (CC), 31 molecular functions (MF), and 65 signaling pathways. HE staining results show that there were no significant differences between Group A and Group B with regard to any of the parameters. Compared with Group A, the levels of the PI3K, p-AKT, and p-mTOR proteins and PI3K, AKT, and mTOR mRNAs in Group B decreased (P < 0.01). CONCLUSIONS: The decline of erectile function in a rat model of migraine was associated with the PI3K/Akt/mTOR signaling pathway.

Transforming growth factor­ß1 functions as a competitive endogenous RNA that ameliorates intracranial hemorrhage injury by sponging microRNA­93­5p.

Intracerebral hemorrhage (ICH) has the highest mortality rate of all stroke subtypes but an effective treatment has yet to be clinically implemented. Transforming growth factor­ß1 (TGF­ß1) has been reported to modulate microglia­mediated neuroinflammation after ICH and promote functional recovery; however, the underlying mechanisms remain unclear. Non­coding RNAs such as microRNAs (miRNAs) and competitive endogenous RNAs (ceRNAs) have surfaced as critical regulators in human disease. A known miR­93 target, nuclear factor erythroid 2­related factor 2 (Nrf2), has been shown to be neuroprotective after ICH. It was hypothesized that TGF­ß1 functions as a ceRNA that sponges miR­93­5p and thereby ameliorates ICH injury in the brain. Short interfering RNA (siRNA) was used to knock down TGF­ß1 and miR­93 expression was also pharmacologically manipulated to elucidate the mechanistic association between miR­93­5p, Nrf2, and TGF­ß1 in an in vitro model of ICH (thrombin­treated human microglial HMO6 cells). Bioinformatics predictive analyses showed that miR­93­5p could bind to both TGF­ß1 and Nrf2. It was found that neuronal miR­93­5p was dramatically decreased in these HMO6 cells, and similar changes were observed in fresh brain tissue from patients with ICH. Most importantly, luciferase reporter assays were used to demonstrate that miR­93­5p directly targeted Nrf2 to inhibit its expression and the addition of the TGF­ß1 untranslated region restored the levels of Nrf2. Moreover, an miR­93­5p inhibitor increased the expression of TGF­ß1 and Nrf2 and decreased apoptosis. Collectively, these results identified a novel function of TGF­ß1 as a ceRNA that sponges miR­93­5p to increase the expression of neuroprotective Nrf2 and decrease cell death after ICH. The present findings provided evidence to support miR­93­5p as a potential therapeutic target for the treatment of ICH.

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology.

CONTEXT: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE: Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 µg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

Effect of leech-centipede medicine on improving erectile function in diabetes-induced erectile dysfunction rats via PDE5 signalling pathway-related molecules.

CONTEXT: The leech and centipede granules have good curative effects on many diabetic vascular diseases, including diabetes-induced erectile dysfunction (DIED). OBJECTIVE: To explore the effect of leech and centipede on erectile function in rats with diabetes-induced erectile dysfunction and its possible mechanism. MATERIALS AND METHODS: Thirty male Sprague-Dawley DIED rats were randomly divided into the model group (Group M), low-dose group (Group DD), high-dose group (Group DG) and tadalafil group (Group T) (n = 6); diabetic rats were induced by streptozotocin. Apomorphine was used to induce diabetic erectile dysfunction. The 'leech-centipede' granules (0.15 and 0.6 g/kg) were intragastrically administered in the DD and DG groups for 8 weeks. Blood glucose, serum insulin, testosterone, cGMP levels and protein expression changes were measured in each group. RESULTS: After 8 weeks, the erectile function of rats in the DG group significantly improved (1.26 ± 0.73). Penis tissue cGMP levels were higher in the DG group (1.48 ± 0.11) than in the M group (0.58 ± 0.15). Protein and mRNA expression levels of NOS were significantly higher (0.77 ± 0.05; 0.61 ± 0.02) but those of PDE5 (0.43 ± 0.05; 0.61 ± 0.03) were lower in the DG group than in the M group (0.37 ± 0.06; 0.51 ± 0.01; 0.78 ± 0.06; 0.81 ± 0.04). CONCLUSION: The leech-centipede can improve erectile dysfunction in DIED rats by regulating the expression of cGMP, NOS, and PDE5-related molecules in the PDE5 pathway. This study provides a potential mechanism for the treatment of DIED with leech-centipede.