Treating ischemic stroke by improving vascular structure and promoting angiogenesis using Taohong Siwu Decoction: An integrative pharmacology strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Neovessels represent a crucial therapeutic target and strategy for repairing ischemic tissue. Taohong Siwu Decoction (THSWD) exhibits potential in promoting angiogenesis to address ischemic stroke (IS). However, its impact on neovessel structure and function, alongside the underlying molecular mechanisms, remains elusive. AIM OF THE STUDY: Our aim is to investigate the protective effects of THSWD on neovessel structure and function, as well as the associated molecular mechanisms, utilizing an integrative pharmacological approach. MATERIALS AND METHODS: We initially employed behavioral tests, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Haematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), Laser Doppler flowmetry (LDF), Evans blue staining, and immunofluorescence to evaluate the protective effects of THSWD on neovascular structure and function in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Subsequently, we utilized network pharmacology, metabolomics, and experimental validation to elucidate the underlying molecular mechanisms of THSWD in enhancing neovascular structure and function. RESULT: In addition to significantly reducing neurological deficits and cerebral infarct volume, THSWD mitigated pathological damage, blood-brain barrier (BBB) leakage, and cerebral blood flow disruption. Moreover, it preserved neovascular structure and stimulated angiogenesis. THSWD demonstrated potential in ameliorating cerebral microvascular metabolic disturbances including lipoic acid metabolism, fructose and mannose metabolism, purine metabolism, and ether lipid metabolism. Consequently, it exhibited multifaceted therapeutic effects, encompassing anti-inflammatory, antioxidant, energy metabolism modulation, and antiplatelet aggregation properties. CONCLUSION: THSWD exhibited protective effects on cerebral vascular structure and function and facilitated angiogenesis by rectifying cerebral microvascular metabolic disturbances in MCAO/R rats. Furthermore, integrated pharmacology offers a promising approach for studying the intricate traditional Chinese medicine (TCM) system in IS treatment.

Probiotic Consortia Protect the Intestine Against Radiation Injury by Improving Intestinal Epithelial Homeostasis.

PURPOSE: Radiation-induced intestinal injury (RIII) commonly occur during abdominal-pelvic cancer radiation therapy; however, no effective prophylactic or therapeutic agents are available to manage RIII currently. This study aimed to clarify the potential of probiotic consortium supplementation in alleviating RIII. METHODS AND MATERIALS: Male C57BL/6J mice were orally administered a probiotic mixture comprising Bifidobacterium longum BL21, Lactobacillus paracasei LC86, and Lactobacillus plantarum Lp90 for 30 days before exposure to 13 Gy of whole abdominal irradiation. The survival rates, clinical scores, and histologic changes in the intestines of mice were assessed. The impacts of probiotic consortium treatment on intestinal stem cell proliferation, differentiation, and epithelial barrier function; oxidative stress; and inflammatory cytokines were evaluated. A comprehensive examination of the gut microbiota composition was conducted through 16S rRNA sequencing, while changes in metabolites were identified using liquid chromatography-mass spectrometry. RESULTS: The probiotic consortium alleviated RIII, as reflected by increased survival rates, improved clinical scores, and mitigated mucosal injury. The probiotic consortium treatment exhibited enhanced therapeutic effects at the histologic level compared with individual probiotic strains, although there was no corresponding improvement in survival rates and colon length. Moreover, the probiotic consortium stimulated intestinal stem cell proliferation and differentiation, enhanced the integrity of the intestinal epithelial barrier, and regulated redox imbalance and inflammatory responses in irradiated mice. Notably, the treatment induced a restructuring of the gut microbiota composition, particularly enriching short-chain fatty acid-producing bacteria. Metabolomic analysis revealed distinctive metabolic changes associated with the probiotic consortium, including elevated levels of anti-inflammatory and antiradiation metabolites. CONCLUSIONS: The probiotic consortium attenuated RIII by modulating the gut microbiota and metabolites, improving inflammatory symptoms, and regulating oxidative stress. These findings provide new insights into the maintenance of intestinal health with probiotic consortium supplementation and will facilitate the development of probiotic-based therapeutic strategies for RIII in clinical practice.

Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside) confers protection against ionizing radiation-induced intestinal epithelial injury in vitro and in vivo.

The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5+ intestinal stem cells (ISCs) and Ki67+ progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis, suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.

Traumatic main airway rupture successfully rescued by extracorporeal membrane oxygenation: A case report.

The chest is a common site for traumatic injury; however, rupture of the main airway after chest trauma is a rare and potentially fatal condition. The present study demonstrated that extracorporeal membrane oxygenation (ECMO) may serve a crucial role in the effective conventional treatment of patients with severe chest trauma, ECMO was used before tracheal repair surgery to prevent hypoxia during surgery. When effective ventilation of the patient cannot occur without assistance, ECMO support is considered to be essential in ensuring effective gas exchange. This rescue procedure can provide guidance for the treatment of patients suffering from traumatic tracheal rupture and respiratory failure. To summarize, ECMO may be able to improve the treatment experience of patients with traumatic tracheal rupture and increase the treatment success rate of such patients.

Honokiol prevents lung metastasis of triple-negative breast cancer by regulating polarization and recruitment of macrophages.

Metastasis is the leading cause of breast cancer-associated death. Lung metastasis commonly occurs in triple-negative breast cancer (TNBC) metastasis, worsening the TNBC prognosis. Considering their role in tumor progression and metastasis, tumor-associated macrophages (TAMs) are essential therapeutic targets in cancer therapy. Previous studies have demonstrated that honokiol inhibits tumor growth and progression. Here we assessed how honokiol inhibits lung metastasis of TNBC by regulating the polarization of macrophages. We found that honokiol decreased the expression of IL-13-triggered M2 markers like CD206, Arg1, and CCL2, preventing the invasion and migration ability of TNBC cells. The activation of signal transducer and activator of transcription STAT6 and STAT3 was significantly suppressed by honokiol in M2 polarized macrophages. Meanwhile, honokiol increased the expression of LPS/IFNγ-induced M1 markers such as CD11c, iNOS, and IL12 by promoting STAT1 phosphorylation. Besides, honokiol decreased both the ratio of M2/M1 macrophages and the expression of the IL-10/IL-12 gene in lung tissues, thereby inhibiting the proliferation and metastasis of murine breast cancer. Moreover, honokiol reduced the infiltration of macrophages to the lung tissue through the CCL2/CCR2 pathways. These results highlight the potential of honokiol in suppressing TNBC tumor progression and lung metastasis by regulating the polarization and recruitment of macrophages.

Perillaldehyde Mitigates Ionizing Radiation-Induced Intestinal Injury by Inhibiting Ferroptosis via the Nrf2 Signaling Pathway.

SCOPE: Gastrointestinal toxicity is one of the major side effects of abdominopelvic tumor radiotherapy. Studies have shown that perillaldehyde (PAH) has antioxidant, antiinflammatory, antimicrobial activity, and antitumor effects. This study aims to determine whether PAH has radioprotective effects on radiation-induced intestinal injury and explore the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are gavaged with PAH for 7 days, then exposed to a single dose of 13 Gy X-ray total abdominal irradiation (TAI). PAH treatment prolongs the survival time, promotes the survival of crypt cells, attenuates radiation-induced DNA damage, and mitigates intestinal barrier damage in the irradiated mice. PAH also shows radioprotective effects in intestinal crypt organoids and human intestinal epithelial cells (HIEC-6). PAH-mediated radioprotection is associated with the upregulation of nuclear factor erythroid-2 related factor 2 (Nrf2), activation of the antioxidant pathway, and inhibition of ferroptosis. Notably, treatment with the Nrf2 inhibitor ML385 abolishes the protective effects of PAH, indicating that Nrf2 activation is essential for PAH activity. CONCLUSION: PAH inhibits ionizing radiation (IR)-induced ferroptosis and attenuates intestinal injury after irradiation by activating Nrf2 signaling. Therefore, PAH is a promising therapeutic strategy for IR-induced intestinal injury.

NCOA4-mediated ferritinophagy is involved in ionizing radiation-induced ferroptosis of intestinal epithelial cells.

Ferroptosis is a newly recognized form of regulated cell death that is characterized by severe lipid peroxidation initiated by iron overload and the generation of reactive oxygen species (ROS). However, the role of iron in ionizing radiation (IR)-induced intestinal injury has not been fully illustrated yet. In this study, we found that IR induced ferroptosis in intestinal epithelial cells, as indicated by the increase in intracellular iron levels and lipid peroxidation, upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, reduced glutathione peroxidase 4 (GPX4) mRNA and glutathione (GSH) levels, and significant mitochondrial damage. In addition, the iron chelator deferoxamine (DFO) attenuated IR-induced ferroptosis and intestinal injury in vitro and in vivo. Intriguingly, pharmacological inhibition of autophagy with 3-methyladenine (3-MA) mitigated IR-induced ferritin downregulation, iron overload and ferroptosis. IR increased the levels of nuclear receptor coactivator 4 (NCOA4) mRNA and protein. NCOA4 knockdown significantly inhibited the reduction of ferritin, decreased the level of intracellular free iron, and mitigated ferroptosis induced by IR in HIEC cells, indicating that NCOA4-mediated autophagic degradation of ferritin (ferritinophagy) was required for IR-induced ferroptosis. Furthermore, cytoplasmic iron further activated mitoferrin2 (Mfrn2) on the mitochondrial membrane, which in turn increased iron transport into the mitochondria, resulting in increased ROS production and ferroptosis. In addition, mice fed with an iron-deficient diet for 3 weeks showed a significant reversal in the intestinal injury induced by abdominal IR exposure. Taken together, ferroptosis is a novel mechanism of IR-induced intestinal epithelial cytotoxicity, and is dependent on NCOA4-mediated ferritinophagy.

(-)-Epigallocatechin-3-Gallate (EGCG) Modulates the Composition of the Gut Microbiota to Protect Against Radiation-Induced Intestinal Injury in Mice.

The high radiosensitivity of the intestinal epithelium limits the outcomes of radiotherapy against abdominal malignancies, which results in poor prognosis. Currently, no effective prophylactic or therapeutic strategy is available to mitigate radiation toxicity in the intestine. Our previous study revealed that the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) attenuates radiation-induced intestinal injury (RIII). The aim of the present study was to determine the effect of EGCG on the intestinal flora of irradiated mice. EGCG administration reduced radiation-induced intestinal mucosal injury, and significantly increased the number of Lgr5+ intestinal stem cells (ISCs) and Ki67+ crypt cells. In addition, EGCG reversed radiation-induced gut dysbiosis, restored the Firmicutes/Bacteroidetes ratio, and increased the abundance of beneficial bacteria. Our findings provide novel insight into EGCG-mediated remission of RIII, revealing that EGCG could be a potential modulator of gut microbiota to prevent and treat RIII.

Dysbiosis of Gut Microbiota Is Associated With the Progression of Radiation-Induced Intestinal Injury and Is Alleviated by Oral Compound Probiotics in Mouse Model.

The acute radiation-induced intestinal injury (RIII) has raised much concerns and is influenced by non-cytocidal radiation effects including the perturbations in gut microbiota. Although a number of studies have reported alteration in gut microbiota following radiation, little is known about its dynamic variation in the progression of acute RIII. In this study, mouse model were treated with total body irradiation (TBI) of 0, 4, 8 and 12 Gy, and the intestinal tissues and fecal samples were collected at 6 h, 3.5 d and 7 d post radiation. We found that the intestinal injuries were manifested in a radiation dose-dependent manner. Results from 16S rRNA gene sequencing demonstrated that the diversity of gut microbiota was not significantly affected at the prodromal stage of acute RIII, after 6 h of radiation. At the critical stage of acute RIII, after 3.5 d of radiation, the composition of gut microbiota was correlated with the radiation dose. The Pearson's correlation analysis showed that the relative abundances of phylum Proteobacteria, genera Escherichia-Shigella and Eubacterium xylanophilum_group, and species Lactobacillus murinus exhibited linear correlations with radiation dose. At the recovery stage of acute RIII, after 7 d of radiation, the diversity of gut microbiota decreased as a whole, among which the relative abundance of phyla Proteobacteria and Bacteroides increased, while that of phylum Tenericutes and genus Roseburia decreased. The intra-gastric administration of compound probiotics for 14 days improved the survival duration of mice exposed to 9 Gy TBI, alleviated the intestinal epithelial injury and partially restored the diversity of gut microbiota. Our findings suggest that acute RIII is accompanied by the dysbiosis of gut microbiota, including its decreased diversity, reduced abundance of beneficial bacteria and increased abundance of pathogens. The gut microbiota cannot be used as sensitive biomarkers at the prodromal stage in acute RIII, but are potential biomarkers at the critical stage of acute RIII. The dysbiosis is persistent until the recovery stage of acute RIII, and interventions are needed to restore it. The administration of probiotics is an effective strategy to protect against acute RIII and subsequent dysbiosis.

What occurs in colloidal gas aphron-induced separation of titanium dioxide nanoparticles? Particle fate analysis by tracking technologies.

As an important method of enriching, separating and removing nanoparticles, colloidal gas aphrons (CGAs) need to be investigated for the fate and interfacial behaviors of particles during the process. It is beneficial to sufficiently interpreting the process performance and mechanisms. This study employed complementary tracking technologies to analyze the extensively-used engineered nanoparticles - TiO2 nanoparticles (TiO2-NPs) in effluent and floats of CGA process. Results denote that, at the optimum SDS relative dosage of 0.78 mg/mg TiO2, the particle number concentration was largely reduced by 2-4 orders of magnitude based on nanoparticle tracking analysis (NTA) whilst approximately 84.0% of TiO2-NPs were separated according to inductively coupled plasma-mass spectrometry (ICP-MS). NTA shows the change of overall particle dispersion status in the water phase while ICP-MS provides the Ti-related separation effect. Particularly, the particle size variation for the scenario of overdosing CGAs was clearly observed by NTA. Micro-Raman, dynamic laser scattering and small angle laser light scattering exhibited advantages in obtaining the configuration and morphology of flocs. The large flocs with open structure were apt to form and be favorably separated at the appropriate CGA dosage. However, overdosing CGAs weakened the capture capacity of bubbles and gave rise to small and dense aggregates. This work, for the first time, shows the change of nanoparticles in water and solid phases using the important and novel nanoparticle collection method - CGA technology. It also provides a reference to other flotation-related technologies for studying the nanoparticle fate and the process performance.

Combination free foot flaps for digit reconstruction: A retrospective analysis of 37 cases.

Combination foot flaps for digit reconstruction was previously introduced by our group as an alternative method for toe-to-hand transfer. The aim of this study was to analyze our experience with the combination foot flaps and to present the surgical refinements that were introduced. A prospective study was conducted including all combination foot flaps performed at our hospital since September 2009. Surgical refinements that were introduced during this study included island flap for repair of toenail donor site and the use of Z-plasty. The median operation duration was 6.7 hours (range 3.5-13 h). Among 74 flaps, partial necrosis occurred in three flaps (4.1%); two palmar flaps (2.7%) were bulky. Among 37 cases of reconstructed digits, contracture of the first web occurred in one case (1.4%). All the patients were able to walk well and did not complain of any pain or cold intolerance. Wound dehiscence of donor site was observed in three patients (8.1%). Toenail deformity occurred in one case (2.7%). The combination foot flap is a reliable option for digit reconstruction with minimal donor site complications.

A flap based on the plantar digital artery arch branch to improve appearance of reconstructed fingers: Anatomical and clinical application.

AIM: To investigate blood supply features of the flap based on the plantar digital artery arch and arch branch artery, and the treatment of outcomes of reconstructed fingers by the plantar digital artery arch branch island flap. METHODS: Eight fresh foot specimens were employed with red emulsion infusion and microdissection. The vascular organization was observed in the second toe, such as initiation site, the course, and the number of the plantar digital artery arch branch. There were 15 fingers of 13 patients (8 males and 5 females) with finger defects accompanied by toe transfer, using the plantar digital artery arch branch flap inserted in the neck of the second toe to correct the appearance defect caused by a narrow "neck" and a bulbous tip. RESULTS: The intact plantar digital arches were identified in all specimens. The plantar digital artery arch had 5 branches. The range of external diameter of the arch branch was 0.4-0.6 mm. All the plantar digital artery arch branch island flaps and the reconstructed fingers survived. These cases were conducted with a follow-up period for 3-18 months (average, 9 months). All the plantar digital artery arch branch island flaps and reconstructed fingers demonstrated a satisfactory appearance and favorable sense function. The reconstructed finger-tip characteristic was good, with no obvious scar hyperplasia. The range of flexion and extension of reconstructed fingers was favorable as well. CONCLUSIONS: The plantar digital artery arch and arch branch artery possess regular vasa vasorum and abundant vascularity. A flap based on the plantar digital artery arch branch is an ideal selection for plastic surgery of reconstructed fingers.

Replantation or revascularization for the treatment of hand degloving injuries.

PURPOSE: The purpose of this study was to explore effective strategies of replantation or revascularization for the treatment of hand degloving injuries. METHODS: Ten patients who had received replantation or revascularization surgery for hand degloving injury between 2002 and 2014 were included for this study. The average age at the time of surgery was 34.5 years (range 18-49 years). There were nine left and one right hand replantations. The cause of injury was an industrial machine press in all of them. The skin was avulsed from the palm to the distal phalangeal level in five patients, to the middle phalangeal level in four patients, and avulsed from the wrist crease level completely in one patient. All the degloved flaps were revascularized. RESULTS: Both the degloved flap and phalanges survived completely in one patient, and partial survival of the flap occurred in the remaining patients. The patients were followed up from 15 months to 78 months (average, 38.1 months). Sensory recovery of the finger pulp ranged from S2 to S3+. Michigan Hand outcome Questionnaire (MHQ) score ranged from 29 to 96 with an average of 69.5. CONCLUSIONS: Midlateral incision to reduce the secondary damage to the capillaries, repair of more vessels for circulation, application of full-thickness skin grafts to enlarge the survival area, and use of anticoagulation protocols during and postsurgery may be beneficial to improve the replantation survival of the degloved skin.

Combined ipsilateral and contralateral second toe flaps for repair of finger degloving injury.

PURPOSE: The purpose of this report was to retrospectively review the results of treatment of degloving injury of the finger by use of combined ipsilateral second dorsal nail-skin flap and contralateral medial second toe flap. METHODS: From 2010 to 2012, seven fingers in seven patients with complete degloving injuries from the level of middle or distal phalanx were reconstructed with combined ipsilateral second dorsal nail-skin flap and contralateral medial second toe flap. The injured fingers included the index finger in four cases, and middle finger in three cases. The nerves of both the flaps were sutured to the bilateral common digital nerves. The donor site of second toe flap was covered with a full-thickness skin graft. RESULTS: All transferred flaps survived after surgery, and all postoperative courses were uneventful. During the follow-up period (mean of 15 months; ranging 6-20 months), the appearance of the reconstructed fingers was comparable with normal ones. The range of motion of the distal interphalangeal joint averaged 55 ± 5.8 degrees. The two point discrimination of the pulp ranged from 8 to > 15 mm (average, 11.3 mm). All the patients were able to walk without difficulty. The MHQ score averaged 59 ± 4.2 points and Maryland foot rating score averaged 92 ± 4.2 points. CONCLUSION: The ipsilateral second toe dorsal nail-skin flap combined with contralateral medial second toe flap may provide an alternative for the reconstruction of completely degloved fingers at the middle and the distal phalangeal level, with satisfactory functional and cosmetic results.

[Effect of electric acupoint stimulation on shivering in cesarean section].

OBJECTIVE: To explore the efficacy of electric acupoint stimulation on shivering in cesarean section. METHODS: Eighty cases of parturients, under the America Society of Anesthesiologists (ASA) physical status II , were randomized into a transcutaneous electrical acupoint stimulation (TEAS) assisted anesthesia group (group A) and an anesthesia group (group B). Spinal-epidural anesthesia(CSEA) puncture was applied to both groups and 8 mg of 0. 75% bubivacaine was given by spinal injection, the block level was T4 T8. In group A, TEAS was applied before CSEA at paired acupoints-ipsilateral Hegu (LI 4)-Laogong (PC 8) and Sanyinjiao (SP 6)-Zusanli (ST 36) till ending the surgery. The 4 pair of bilateral acupoints were fixed with self-adhesive electrodes and connected with Han's acupoint and nerve stimulator (HANS, LH402H), the frequency was 2 Hz/ 15 Hz, the intensity was 10- 30 mA and the form was densedisperse wave within the patients' tolarance. The heart rate (HR), mean arterial pressure (MAP), oxyhemoglobin saturation (SPO) and shivering degree were recorded before anesthesia (To), 1 min after anesthesia puncture (Ti), 1 min after the delivery (Tz), during abdomen closure (T3) and at the end of surgery (T4). RESULTS: The occurrence rate of shivering was 35. 0% (14/40) in group A, which was lower to 67. 5% (27/40, P<0. 05) in group B; the degree of shivering was lighter in group A than that in group B at T2, T3 and T4 (all P<0. 01). In group A, HR was faster at T1 and T2 compared to that at To (all P<0. 05), while at T3 and T4, the HR was the same with that before anesthesia (all P>0. 05). In group B, the HR was faster at T1, T2, T3 and T4 compared to that at T0 (P<0. 05, P<0. 01). In both groups, the MAP was lower at T1, T2 (P<0.05,P<0.01) and resumed to that before anesthesia at T3 and T4 (all P>0.05); there was no statistical significance of SPO2 in both groups (all P>0.05). CONCLUSION: TEAS can reduce the occurrence rate of shivering and steady the heart rate in cesarean section.