Histology Reaction Research Articles

Imperatorin's Effect on Myocardial Infarction Based on Network Pharmacology and Molecular Docking.

Purpose: Myocardial infarction (MI), a severe cardiovascular disease, is the result of insufficient blood supply to the myocardium. Despite the improvements of conventional therapies, new approaches are needed to improve the outcome post-MI. Imperatorin is a natural compound with multiple pharmacological properties and potential cardioprotective effects. Therefore, this work investigated imperatorin's therapeutic effects and its mechanism of action in an MI mouse model. Methods: Network pharmacology, molecular docking, and experimental validation were performed for exploring the pharmacokinetic properties, therapeutic effects, and molecular targets of imperatorin in MI. Permanent ligation of the left anterior descending artery was performed in male C57BL/6 mice to induce MI before treatment with imperatorin once per day for 1 week. Echocardiography, heart histology, RNA sequencing, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) as well as western blotting were carried out for evaluating cardiac function and structure, as well as gene and protein expression. Results: Imperatorin significantly improved cardiac function, preserved cardiac structure, attenuated cardiac remodeling and fibrosis, and reduced cardiomyocyte apoptosis in MI mice. Eight differentially expressed genes overlapping with key target genes were found, two upregulated and six downregulated. A key target in signaling pathways associated with imperatorin effect in MI was angiotensin-converting enzyme (ACE). Imperatorin inhibited ACE-angiotensin II (Ang II)-angiotensin II Type 1 receptor (AT1R) axis in MI mice. Conclusion: Imperatorin attenuated MI by inhibiting the ACE-Ang II-AT1R axis. Thus, imperatorin might be considered a potential therapeutic agent to cure MI.

Gelatin/polycaprolactone membranes promote endometrial regeneration and restore fertility

Objective To investigate the effectiveness of gelatin/polycaprolactone (GT/PCL) membranes for restoring endometrial structure and function and fertility in a rat model of endometrial injury. Methods We randomized 125 female Sprague-Dawley (SD) rats to the sham, natural repair (NR), estrogen (E), GT/PCL, and E-GT/PCL groups. Except for the sham group, all rats underwent uterine curettage. After 1, 2, 3, and 4 weeks, 12 rats from each group were sacrificed; their uterine tissue was collected for histological, immunohistochemical, and reverse transcription quantitative-polymerase chain reaction analyses. Eight rats from each group underwent radiography of the uterine cavity. The remaining 25 females were mated with males to assess fertility 60 d postoperatively. Results The GT/PCL and E-GT/PCL groups had higher endometrial thickness, collagen degradation, cytokeratin 19, vimentin (VIM) expression, and microvessel densities and had higher levels of estrogen receptors (ERα) but lower levels of tumor necrosis factor (TNF) than the NR and E groups. They also showed better hysterographic patency, with the shape of the uterine cavity similar to that of the sham group, and higher embryo implantation rates than the NR and E groups. Conclusions GT/PCL membranes promote endometrial regeneration and improve fertility in rats. They may help prevent intrauterine adhesions (IUAs) postoperatively and warrant further investigation.

Histologic Reaction Patterns of Lymph Node Involvement in Ovarian Serous Borderline Tumors.

Lymph node (LN) involvement (LNI) is not infrequently observed in ovarian serous borderline tumors (SBTs) but is not considered equivalent to malignant tumor metastasis, as it reportedly does not impact recurrence or survival in patients with SBT. However, the reasons underlying the insignificant clinical impact of LNI remain unclear. To determine whether histologic reaction patterns (HRPs) are associated with SBT prognosis. We compared HRPs around tumor cell clusters in LNs of patients with SBT and low-grade serous carcinoma. HRPs were classified into 4 categories (HRP 1-HRP 4) based on tumor cell location in LNs, the presence of their adhesion to surrounding lymphoid tissue, or pericellular desmoplastic reactions. Although LNI itself was linked to reduced recurrence-free survival (RFS), no recurrence was observed in patients with HRP 1 or 2, characterized by freely floating tumor cells in the lumens of afferent/efferent lymphatics or intranodal sinus with surrounding free spaces. Conversely, HRP 3 or higher, characterized by firm tumor cell adhesion to lymphoid tissue (HRP 3) or peritumoral desmoplastic reaction (HRP 4), independently impacted RFS, albeit not overall survival. The prognosis of SBT with LNI is not uniformly favorable, and HRPs around the LNI significantly influence patient outcomes. Patients with firm tumor cell adhesion to surrounding tissue, with or without peritumoral desmoplastic reaction (HRP ≥3), independently experience decreased RFS, although this does not correlate with reduced overall survival.

Effect of zinc or copper supplementation on the efficacy and sustainability of botulinum toxin A “Botox” injection in masseter muscle of albino rats

ObjectivesThis study aimed to evaluate whether oral zinc or copper supplementation affected the efficacy and sustainability of botulinum toxin-A (BTX-A) injection in masseter muscle of albino rats. Materials and methods32 adult male albino rats were allocated equally into four groups: group I (control), group II received 10U BTX-A injection, group III received 10U BTX-A injection + zinc (1 mg, 4 days pre-injection), and group IV received 10U BTX-A injection + copper (0.04 mg, 7 days post-injection). Rats were euthanized at 2 and 12 weeks (4 rats per subgroup) after injection. The masseter muscle was examined via histological, histochemical, histomorphometrical and real-time polymerase chain reaction (qRT-PCR) analyses. ResultsThe histopathological results of the BTX-A group showed atrophied muscle fibers with increased atrophy with time compared to the control group. The BTX-A + zinc group displayed more atrophy compared to BTX-A group. Conversely, the BTX-A + copper group demonstrated improved histology of muscle fibers compared to BTX-A and BTX-A + zinc groups. Histomorphometric analysis of Masson trichrome staining at 2 and 12 weeks revealed that collagen area percentage was the highest in the BTX-A + copper and control groups, followed by BTX-A and BTX-A + zinc groups. At 12 weeks, the nuclear factor kappa beta (NF-κB) mRNA expression was significantly higher in BTX-A + zinc and BTX-A groups compared to BTX-A + copper group and relative to the control group. ConclusionZinc supplementation significantly improved the effectiveness and durability of BTX-A, whereas copper supplementation reduced its efficacy.

Thyme and Oregano Oil Potential Therapeutics against Malathion Toxicity through Biochemical, Histological, and Cytochrome P450 1A2 Activities in Male Wistar Rats.

The widespread use of malathion may offer several hazards to humans and animals; additionally, many medicinal plants provide what is known as a broad antitoxicity treatment. This study was carried out to investigate hazardous biochemical and histological reactions to MOP and evaluate the effectiveness of TEO and OEO essential oils in restoring normal physiological conditions after MOP exposure by measuring enzyme-specific activity for Cytochrome P450 1A2 (CYP1A2). One hundred and twenty rats were divided into six groups of twenty animals each: (i) C - MOP served as the control group, (ii) C + MOP treated with 5 mg/kg/BW of Malathion-D10, (iii) TEO treated with 100 mg/kg/BW of oregano essential oil, (iv) TEO treated with 100 mg/kg/BW of thyme essential oil, (v) MOP + OEO treated with 5 mg/kg/BW of Malathion-D10 and 100 mg/kg/BW of oregano essential oil, and (vi) MOP + TEO treated with 5 mg/kg/BW of Malathion-D10 and 100 mg/kg/BW of thyme essential oil. The results indicated the protective effects of OEO and TEO against MOP-induced weight loss. Additionally, there was a significant improvement in ALT, AST, and ALK-Ph after being treated with OEO and TEO, either alone or after MOP exposure. Also, treatment with OEO and TEO ameliorated these oxidative stress parameters, indicating their antioxidative properties. A histopathological examination of liver tissues showed reduced hepatocellular damage and improved liver architecture in the OEO and TEO, both alone and in combination with MOP, and protective effects were more pronounced in the TEO-treated groups. However, the results indicated that TEO was more effective than OEO in increasing CYP1A2 expression and alleviating MOP-induced toxicity. Specifically, TEO showed higher protein expression and therapeutic action in reducing liver damage. In conclusion, these findings suggest that OEO and TEO may be potent therapeutic agents against MOP toxicity, offering protective effects by enhancing CYP1A2 activity and mitigating organ damage. Such knowledge would be an important step toward developing potentially unique treatment options for natural antitoxins.

Chitosan-glucose derivative membrane obtained by Maillard reaction improves cartilage repair in a rabbit model

BackgroundTreatment of articular cartilage injury remains a challenging clinical problem in orthopedics. Chitosan-derived biomaterial could be a potential adjuvant treatment to improve cartilage repair. In the current study, we examined the effects of two potential chitosan-derived materials on cartilage regeneration of osteochondral defects in rabbits.MethodsAn osteochondral defect was created over the rabbit knee and treated using three approaches: group A received no material (n = 24), group B received chitosan membranes with glucose absorption (CGA; n = 25), and group C received chitosan-glucose derivative membranes obtained via the Maillard reaction (CGMR; n = 25). Cartilage repair over the osteochondral defect was analyzed 12 weeks post-surgery via histological analysis, immunostaining, and reverse transcription-qualitative polymerase chain reaction (RT-qPCR) for type-I and type-II collagen mRNA.ResultsAccording to histological analysis, CGMR-treated defects showed significantly improved modified O’Driscoll scoring when compared with no material- and CGA-treated defects (20.9 ± 4.3 vs. 13.00 ± 2.5 and 17.7 ± 4.6, p < 0.001). Moreover, group C exhibited higher intensity of type-II collagen immunohistochemical staining over the regenerated cartilage than groups A and B, along with increased expression of type-II collagen mRNA by RT-qPCR.ConclusionsCGMR might improve cartilage regeneration in osteochondral defects.

Pirfenidone targeted mechanisms for alleviating methotrexate-induced testiculopathy in Wistar rats.

Testicular injury and affected spermatogenesis are major complications of methotrexate (MTX) use. Oxidative stress is one contributing process leading to inflammation and apoptosis induction. Pirfenidone (PFD) is a well-known anti-fibrotic drug prescribed for interstitial lung fibrosis, in addition to anti-inflammatory, antioxidative, and antiapoptotic capabilities. The study aimed to explore the potential protection afforded by PFD in a rat model of MTX-induced testiculopathy. The experimental design included four groups, each containing seven adult Wistar rats: control, PFD (500mg/kg/day, orally)-, MTX (0.5mg/kg, intraperitoneal, twice weekly)-, and PFD/MTX-treated groups. Treatment continued for 4weeks. Blood and testicular samples were harvested for biochemical, histological, immunohistochemical, and polymerase chain reaction (PCR) analyses. Also, the testicular damage and spermatogenic activity were graded by the testicular injury and Johnsen scoring system, respectively. PFD positively affected the serum testosterone (TST) level, reduced the testicular inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)], reduced the testicular oxidative burden, increased superoxide dismutase (SOD), and protected the testicular histological structure. In addition, antifibrotic effects, anti-caspase-3, and PCNA enhancement activity were recorded. PFD exhibited a protective potential and mitigated the MTX-induced testiculopathy via suppression of testicular oxidative stress, inflammation, fibrosis, and apoptosis and retaining the testicular proliferative efficacy as confirmed by histological, immunohistochemical, and biochemical methods.

Efficiency of Thyme and Oregano Essential Oils in Counteracting the Hazardous Effects of Malathion in Rats.

The widespread use of MLT may pose numerous hazards to animal breeding, health, and resilience due to the presence of MLT residues in animal feedstuffs, pastures, hay, and cereals. Many medicinal plants provide what is called a generalized anti-toxic remedy. The current study examined hazardous biochemical and histological reactions to MLT and the efficiency of ThEO and OEO essential oils as anti-toxic therapies to return to a natural state after MLT exposure. A total of 75 male albino rats were randomly assigned to two groups: (i) C - MLT, comprising 25 rats, served as the control group; and (ii) C + MLT, with 50 rats that were exposed to 5 mg/kg/BW. After exposure to MLT for 21 days, a return to normal status was determined by subdividing the C + MLT group into two equal groups: ThEO and OEO were used as treatments, with 100 mg/kg body weight of thyme and oregano essential oils, respectively, being administered for 21 days. The results showed a significant decrease in body weight gain (BWG) and final weight (FW) compared to C - MLT, while the therapeutic effects of ThEO and OEO enhanced FW and BWG. Our results indicated that MLT exposure resulted in deficient serum liver function, but that OEO and ThEO therapy brought about a significant improvement in liver enzyme function. Although there was no significant difference in serum aspartate transaminase (AST) or alkaline phosphatase (ALK-Ph) and a significant drop in alanine transaminase (ALT) and acetyl choline-esterase (AChE) levels, the C + MLT group showed hepatic fibrosis in the third stage. Furthermore, histological sections of the OEO and ThEO groups showed reduced hepatocellular damage, inflammation, and hepatic fibrosis. However, there was a significant increase in serum creatinine between the C + MLT and C - MLT groups following exposure to MLT. Histological sections of renal tissue from rats treated with OEO and ThEO showed reduced tubular damage, reduced interstitial inflammation, and preserved renal tissue architecture. In conclusion, OEO and ThEO are potential compounds for use as anti-toxic therapies to return to a natural state after MLT exposure. These compounds could serve as an experimental therapeutic approach against natural toxins, providing a solution to the problems of raising livestock that are exposed to nutritional toxicity.

Effect of fractional picosecond laser therapy using a diffractive optical lens on histological tissue reaction

ABSTRACT Background and Objectives Fractional ablative resurfacing techniques are preferred treatments for facial rejuvenation of aged skin. This study was performed to investigate the cutaneous effects of using a fractional picosecond laser at 1064 nm with a diffractive lens. Methods The penetration depth according to the location of the handpiece tip was evaluated using an acrylic panel. Laser induced optical breakdown (LIOB) and cutaneous damage were observed after hematoxylin and eosin staining in guinea pigs. Collagen formation was evaluated using Victoria staining, Masson’s trichrome (MT) staining, and immunohistochemical staining for collagen type III. Results The penetration depth for LEVEL 1 was 499.98–935.23 μm (average: 668.75 ± 182.84 μm); the LIOB cavity area was 1664.17 ± 650.52 μm2. The penetration depth of LEVEL 2 was 257.12–287.38 μm (average: 269.77 ± 14.55 μm) with an LIOB cavity area of 1335.85 ± 214.41 μm2. At LEVEL 3, that was 36.17–53.69 μm (average: 52.15 ± 20.81 μm) and the LIOB cavity area was 1312.67 ± 1069.12 μm2. No epidermal tissue damage was observed and collagen formation was observed from day 14 under all conditions. Conclusion Diffractive optical element (DOE) lens arranged laser treatment system controlled the position of LIOB occurrence and an irradiating area.

Curcumin-Polyethylene Glycol Loaded on Chitosan-Gelatin Nanoparticles Enhances Infected Wound Healing.

The aim of the present study was to evaluate effects of curcumin-polyethylene glycol loaded on chitosan-gelatin nanoparticles (C-PEG-CGNPs) on healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in rat as a model study. Forty male Wistar rats were randomized into 5 groups of 8 animals each. In CNTRL group, no infected/no treated wounds were covered with sterile saline 0.9% solution (0.1 mL). In MRSA group, MRSA-infected wounds were only treated with sterile saline 0.9% solution (0.1 mL). In MRSA/CP group, 0.1 mL curcumin nanoparticles (1 mg/mL) was applied topically to treat MRSA-infected wounds. In MRSA/CG group, 0.1 mL CG (1 mg/mL) was applied topically to treat MRSA-infected wounds. In MRSA/CP-CG group, 0.1 mL CP-CG (1 mg/mL) was applied topically to treat MRSA-infected wounds. Microbiological examination; planimetric, biochemical, histological, morphometric studies, angiogenesis, hydroxyproline levels, and reverse transcription polymerase chain reaction for caspase 3, Bcl-2, and p53 showed significant difference between rats in MRSA/CP-CG group in comparison with other groups (P < .05). Accelerated and improved healing in wounds infected with MRSA were observed in animals treated with C-PEG-CGNPs. Via increasing solubility of curcumin in C-PEG-CGNP, this harmless and easily available composition could be considered to be topically applied in infected wounds.

Electrical signature of heterogeneous human mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) have gained traction in transplantation therapy due to their immunomodulatory, paracrine, immune-evasive, and multipotent differentiation potential. The inherent heterogeneity of hMSCs poses a challenge for therapeutic treatments and necessitates the identification of robust biomarkers to ensure reproducibility in both in vivo and in vitro experiments. In this study, we utilized dielectrophoresis (DEP), a label-free electrokinetic phenomenon, to investigate the heterogeneity of hMSCs derived from bone marrow (BM) and adipose tissue (AD). The electrical properties of BM-hMSCs were compared to homogeneous mouse fibroblasts (NIH-3T3), human fibroblasts (WS1), and human embryonic kidney cells (HEK-293). The DEP profile of BM-hMSCs differed most from HEK-293 cells. We compared the DEP profiles of BM-hMSCs and AD-hMSCs and found that they have similar membrane capacitances, differing cytoplasm conductivity, and transient slopes. Inducing both populations to differentiate into adipocyte and osteoblast cells revealed that they behave differently in response to differentiation-inducing cytokines. Histology and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses of the differentiation-related genes revealed differences in heterogeneity between BM-hMSCs and AD-hMSCs. The differentiation profiles correlate well with the DEP profiles developed and indicate differences in the heterogeneity of BM-hMSCs and AD-hMSCs. Our results demonstrate that using DEP, membrane capacitance, cytoplasm conductivity, and transient slope can uniquely characterize the inherent heterogeneity of hMSCs to guide robust and reproducible stem cell transplantation therapies.

Comparative diagnostic performance of rapid urease test with the sweeping method versus tissue sampling method after Helicobacter pylori eradication (with video)

The rapid urease test (RUT) is widely used to detect Helicobacter pylori infection; however, it is not preferred as a monitoring strategy after eradication owing to its low sensitivity. In this study, we evaluated the diagnostic performance of RUT using the sweeping method, which overcomes the limitations of conventional tissue sampling methods after eradication. Patients who received H pylori eradication treatment were enrolled. Each of the sweeping and conventional methods was performed on the same patients to compare diagnostic performance. Urea breath test (UBT), histology, and polymerase chain reaction were performed to determine true infection. Logistic regression analysis was conducted to investigate reasons for discrepancies between the results of the 2 methods. In 216 patients, the eradication success rate was 68.1%, and the sensitivity and specificity of the sweeping method were 0.812 and 0.912, respectively, whereas those of the conventional method were 0.391 and 0.993, respectively (P< .05 for all). The area under the receiver operating characteristic curve for the sweeping method was higher than that for the conventional method (0.862 vs 0.692, P< .001). The mean time to H pylori detection for the sweeping method was 4.7 ± 4.4 minutes and 12.3 ± 16.1 minutes for the conventional method (P< .001). The risk for inconsistent results between the 2 methods was the highest for UBT values of 1.4‰ to 2.4‰ (odds ratio, 3.8; P= .016). The RUT with the sweeping method could potentially replace the tissue sampling method as a test to confirm H pylori eradication and be an alternative option to UBT for patients requiring endoscopy.

Metal nanoparticle-induced effects on green toads (Amphibia, Anura) under climate change: conservation implications.

The toxicity of aluminum oxide (Al2O3), copper oxide (CuO), iron oxide (Fe3O4), nickel oxide (NiO), zinc oxide (ZnO), and titanium dioxide (TiO2) nanoparticles (NPs) on amphibians and their interaction with high temperatures, remain unknown. In this study, we investigated the survival, developmental, behavioral, and histological reactions of Bufotes viridis embryos and larvae exposed to different NPs for a duration of 10 days, using lethal concentrations (LC25%, LC50%, and LC75% mg/L) under both ambient (AT: 18 °C) and high (HT: 21 °C) temperatures. Based on LC, NiONPs > ZnONPs > CuONPs > Al2O3NPs > TiO2NPs > Fe3O4NPs showed the highest mortality at AT. A similar pattern was observed at HT, although mortality occurred at lower concentrations and Fe3O4NPs were more toxic than TiO2NPs. The results indicated that increasing concentrations of NPs significantly reduced hatching rates, except for TiO2NPs. Survival rates decreased, abnormality rates increased, and developmental processes slowed down, particularly for NiONPs and ZnONPs, under HT conditions. However, exposure to low concentrations of Fe3O4NPs for up to 7 days, CuONPs for up to 72 h, and NiO, ZnONPs, and TiO2NPs for up to 96 h did not have a negative impact on survival compared with the control group under AT. In behavioral tests with larvae, NPs generally induced hypoactivity at AT and hyperactivity at HT. Histological findings revealed liver and internal gill tissue lesions, and an increase in the number of melanomacrophage centers at HT. These results suggest that global warming may exacerbate the toxicity of metal oxide NPs to amphibians, emphasizing the need for further research and conservation efforts in this context.

Histological and biochemical changes in a rat rotator cuff tear model with or without the subacromial bursa

The subacromial bursa (SAB) plays an important role in the tendon healing process. Based on previous reports, co-culture of the rotator cuff (RC) and SAB have been shown to increase the tendon-related gene expressions, inflammatory cytokines, and tensile strength. However, the nature of the specific biochemical alterations during the inflammatory and repair phases of tendon healing with or without the SAB remain unknown. Using a full-thickness RC tear rat model, we determined how the presence or absence of the SAB alters the histological characteristics and gene expressions. After 3 and 6 weeks, tissues were collected for histological and real-time quantitative polymerase chain reaction (RT-qPCR) evaluations. Results showed greater cell density at 3 weeks, neovascularization and tendon thickening at 6 weeks with SAB preservation. Immunostaining revealed significant increases in type 3 collagen (COL3) expression at 6 weeks with SAB preservation. The RT-qPCR results showed that SAB preservation induced significant increases in the expression of scleraxis, matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) at 3 weeks and significant increases in COL3, IL-10, and arginase-1 (Arg-1) at 6 weeks. An RC tear undergoes more appropriate inflammatory and repair phases during the tendon healing process when the SAB is retained.

Thick silk fibroin vascular graft: A promising tissue-engineered scaffold material for abdominal vein grafts in middle-sized mammals.

Abdominal vein replacement with synthetic tissue-engineered vascular grafts constructed from silk-based scaffold material has not been reported in middle-sized mammals. Fourteen canines that underwent caudal vena cava replacement with a silk fibroin (SF) vascular graft (15 mm long and 8 mm diameter) prepared with natural silk biocompatible thread were allocated to two groups, thin and thick SF groups, based on the graft wall thickness. The short-term patency rate and histologic reactions were compared. The patency rate at 2 weeks after replacement in the thin and thick SF groups was 50% and 88%, respectively (p = 0.04). CD31-positive endothelial cells covered the luminal surface of both groups at 4 weeks. The elastic modulus of the thick SF graft was significantly better than that of the thin SF graft (0.0210 and 0.0007 N/m2, p < 0.01). Roundness of thick SF groups (o = 0.8 mm) was better than thin SF (o = 2.0 mm). There was significant difference between the groups (p = 0.01). SF vascular grafts are a promising tissue-engineered scaffold material for abdominal venous system replacement in middle-sized mammals, with thick-walled grafts being superior to thin-walled grafts.

Acute histological reactions in the otolith organs to inner ear drug delivery through a cochlear implant.

Cochlear implantation is currently regarded as a safe and minimally invasive procedure. However, cochlear implantation can have an impact on vestibular function, despite the lack of correlation between patient symptomatology and damage in vestibular tests. Thus, the present study aims to analyze the presence of hydrops and histological reactions at the level of the vestibule after cochlear implantation with dexamethasone pump delivery in Macaca fascicularis (Mf). A detailed histological study was conducted on a total of 11 Mf. All 11 Mf were divided into three groups: 5 Mf were implanted with an electrode array HL-14 connected to a pump delivering FITC-dextran for 24 h (Group A); 4 Mf were implanted with a CI electrode array attached to a pump for FITC-dextran delivery for 7 days (Group B); and 2 Mf were considered the control group, without any kind of cochlear device implantation (Group C). After drug deliver, the selected macaques were euthanized to collect tissue samples for histological analysis. An experienced observer, focusing on the utricle and saccule areas, conducted a blinded inner ear histology analysis. Surgical procedures were successfully performed in all cases. No signs of cochlear reaction to the device were observed, including neither collapse nor fibrosis. Endolymphatic sinus dilatation was observed in Mf4A and Mf3B, while cochlear hydrops was observed in Mf3A. The mean areas of the utricle and saccule exhibited some statistically significant differences, specifically, in the saccule between groups C and both groups A (p = 0.028) and B (p = 0.029); however, no significant differences were observed between groups A and B or among comparisons of the utricle. A significant concern relates to the safety of cochlear implantation with regard to vestibular preservation and hearing. New advancements in electrode arrays, such as CI devices coupled with delivery pumps, pose a challenge in maintaining minimally traumatic surgical concept-based procedures without affecting the inner ear homeostasis. The implantation of this device may cause vestibular hydrops in the saccule, indicating that the longer the time of substance release, the greater the grade of hydrops evidenced at the saccular level. Apart from this finding, the risk of histological damage to the vestibule is low.

Metformin Eliminates Lymphedema in Mice by Alleviating Inflammation and Fibrosis: Implications for Human Therapy.

Secondary lymphedema is a chronic, disabling disease affecting more than 50% of patients with cancer and lacking effective pharmacologic treatment even for early to middle disease stages. Metformin reportedly exerts anti-inflammatory and antifibrotic effects and is safe, with minimal side effects. The authors investigated the role of metformin in lymphedema mouse models and examined underlying molecular mechanisms. Male C57BL/6 mice (6 to 8 weeks old; n = 15/group) received metformin (300 mg/kg/day) by gavage on day 3 after lymphedema surgery; saline and sham groups were administered the same volume of saline. Hindlimb circumference and tail volume were monitored every 2 days. On day 28, samples were collected for histologic assessment, Western blotting, and reverse transcription quantitative polymerase chain reaction analysis of inflammation, fibrosis, and AMP-activated protein kinase (AMPK) expression. AMPK activity was assayed in patients with secondary lymphedema (International Society of Lymphology stage II) and controls following strict inclusion criteria. Compared with the saline group, the metformin group exhibited hindlimb circumference and tail volume reduced by 469.70% and 305.18%, respectively, on day 28. Dermal thickness was reduced by 38.27% and 72.57% in the hindlimbs and tail, respectively. Metformin decreased CD4+ T-cell infiltration by 19.73%, and decreased expression levels of interleukin-4, interleukin-13, interleukin-17, and transforming growth factor-β1. In addition, it lowered collagen I deposition by 33.18%. Compared with the saline group, the number of lymphatic vessels increased by 229.96% in the metformin group. Both the saline group mice and patients with lymphedema showed reduced AMPK activity; metformin increased p-AMPK expression by 106.12%. Metformin alleviated inflammation and fibrosis and increased lymphangiogenesis in lymphedema mouse models by activating AMPK signaling. Metformin provides preliminary evidence as a potential therapeutic option for lymphedema.

A novel and efficient murine model for investigating tendon-to-bone healing

BackgroundTendon-to-bone healing is a critical challenge in sports medicine, with its cellular and molecular mechanisms yet to be explored. An efficient murine model could significantly advance our understanding of this process. However, most existing murine animal models face limitations, including a propensity for bleeding, restricted operational space, and a steep learning curve. Thus, the need for a novel and efficient murine animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing is becoming increasingly evident.MethodsIn our study, forty-four 9-week-old male C57/BL6 mice underwent transection and reattachment of the Achilles tendon insertion to investigate tendon-to-bone healing. At 2 and 4 weeks postoperatively, mice were killed for histological, Micro-CT, biomechanical, and real-time polymerase chain reaction tests.ResultsHistological staining revealed that the original tissue structure was disrupted and replaced by a fibrovascular scar. Although glycosaminoglycan deposition was present in the cartilage area, the native structure had been destroyed. Biomechanical tests showed that the failure force constituted approximately 44.2% and 77.5% of that in intact tissues, and the ultimate tensile strength increased from 2 to 4 weeks postoperatively. Micro-CT imaging demonstrated a gradual healing process in the bone tunnel from 2 to 4 weeks postoperatively. The expression levels of ACAN, SOX9, Collagen I, and MMPs were detected, with all genes being overexpressed compared to the control group and maintaining high levels at 2 and 4 weeks postoperatively.ConclusionsOur results demonstrate that the healing process in our model is aligned with the natural healing process, suggesting the potential for creating a new, efficient, and reproducible mouse animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing.Graphical abstract

Knockout of the Tnfa Gene Decreases Influenza Virus-Induced Histological Reactions in Laboratory Mice.

Tumor necrosis factor alpha (TNF-α) is a cytokine that is responsible for many processes associated with immune response and inflammation. It is involved in the development of an antiviral response to many virus infections. This factor was shown to be activated in influenza A virus infection, which enhances production of other cytokines. The overexpression of these cytokines can lead to a cytokine storm. To study the role of TNF-α in the development of pathologies associated with viral infection, we generated a Tnfa knockout mouse strain. We demonstrated that these mice were characterized by a significant increase in the number of viral genomes compared to that in the parental strain, but the amount of live virus did not differ. A histopathology of the lungs in the genetically modified animals was significantly lower in terms of interalveolar septal infiltration. The generated model may be used to further study pathological processes in viral infections.

Impact of peripheral blood mononuclear cells preconditioned by activated platelet supernatant in managing gastric mucosal damage induced by zinc oxide nanoparticles in rats.

The world has witnessed tremendous advancements in nano-base applications. Zinc oxide nanoparticles (ZON) are widely used in food industry and medicine. Although their application is of important value, they may cause toxicity to body tissues. Peripheral blood mononuclear cells (PBMCs) proved its efficacy in tissue regeneration especially when it is preconditioned by activated platelet supernatant (APS). The aim of this study is to evaluate the effect of ZON on the gastric mucosa and the therapeutic role of the PBMCs preconditioned by APS in rats. Ten rats were donors and fifty rats were recipients. The recipients were divided into; control group, ZON group (10 mg/kg/day orally for five days) and preconditioned PBMCs group (1×107 once intravenously 24 hours after ZON). Gastric specimens were processed for histological, immunohistochemical, biochemical and quantitative real-time polymerase chain reaction studies. ZON group showed marked structural changes in the gastric mucosa. There was desquamation or deep ulceration of the epithelium. Cytoplasmic vacuoles and pyknotic nuclei were in glandular cells. Reduced proliferating cell nuclear antigen and increased tumor necrosis factor-α were in epithelial cells. There were significant elevation in malondialdahyde and reduction in glutathione, superoxide dismutase, and catalase. Enhancement in mRNA expression of nuclear factor kappa-B and cyclooxygenase-2 was detected. The preconditioned PBMCs group showed significant improvement of all parameters. So, ZON had cytotoxic effects on the gastric mucosa and the preconditioned PBMCs had a therapeutic effect on gastric mucosal damage after ZON.