Regenerative Changes Research Articles

Antidiabetic and Hypolipidemic Effect of Ethanolic Seed Extract of Prosopis juliflora in Fructose Induced Hyperglycemia in Rats

Objective: To evaluate the antidiabetic and hypolipidemic effect of ethanolic seed extract of Prosopis juliflora in fructose induced hyperglycemia in wistar albino rats in comparison with Metformin. Materials and methods: 30 male wistar albino rats were divided equally into 5 groups. Group I and II were the normal and the disease control groups. While, groups III to V were the treatment groups. Animals in group I received regular drinking water; whereas, groups II to V received 20% fructose water for 8 weeks. After 8 weeks, animals in groups II to V had elevated fasting blood sugar, HOMA-IR, weight gain and dyslipidemia. From week 9 to 16 group I animals continued to receive regular drinking water, group II received 2ml of distilled water and groups III, IV and V received Metformin 200mg/kg, P.juliflora extract 400mg/kg and 600mg/kg respectively in addition to 20% fructose water. The animals were sacrificed at the end of 16 weeks and histopathological examination of pancreas was done. Biochemical and hematological assessments were done at baseline and at 16 weeks to assess safety of the interventions. Results: When compared to the disease control group, animals in group III treated with metformin and groups IV and V treated with P.juliflora extract at doses of 400mg/kg and 600mg/kg showed a significant decrease in Fasting blood glucose, HOMA-IR and improvement in lipid profile. Even though both the doses of the extract showed significant pharmacological activity, 600mg/kg showed better activity equivalent to metformin. Histopathological examination of pancreas showed regenerative changes in the metformin and P.juliflora 600mg/kg treated groups. No significant abnormality was observed in the biochemical and haematological parameters at the end of the study. Conclusion: P.juliflora seed extract in the dose 400 mg/kg and 600mg/kg exhibited antidiabetic and hypolipidemic activity with no significant adverse events, in this study. Both the doses were having anti dyslipidemic effect similar to metformin whereas 600 mg/kg dose of P.juliflora was having better antidiabetic effect comparable to Metformin. Keywords: Diabetes, Dyslipidemia, P.juliflora, Fructose, Metformin, Metabolic syndrome

Solutions and insights for agricultural monitoring, reporting, and verification (MRV) from three consecutive issuances of soil carbon credits

Regenerative agricultural practice adoption on conventionally managed fields has gained momentum as a climate mitigation strategy, given the ability of these practices to sequester carbon or reduce greenhouse gas emissions. However, the geospatial and temporal variability of the impact of specific practices, such as cover cropping or no-till, pose challenges for scalable quantification of emissions reduction and deploying incentives to drive increased adoption. To quantify impact while accounting for variability and uncertainty at scale, Indigo Ag created a monitoring, reporting, and verification (MRV) pipeline to produce agricultural soil carbon credits produced at large scales (hundreds of thousands of hectares). The pipeline ingests field data from enrolled farmers, checks data quality, uses hybrid soil sampling and biogeochemical modeling to produce estimates of emissions reduction and uncertainty, and then applies deductions based on calculated uncertainty and leakage to quantify total project-wide carbon credits and monitor for durability of carbon. The implementation of a carbon project (CAR1459) from 2018 to 2022 on 553,743 ha of U.S. cropland utilizing the pipeline is estimated to have reduced emissions by 398,408.5 tCO2e, amounting to 296,662 tCO2e of soil carbon credits after uncertainty deductions. This paper explores the effect sizes associated with specific regenerative practice changes across the project domain. Cover cropping consistently resulted in a net positive climate impact and reduced emissions by 1.29 tCO2e per hectare per year, on average. Introduction of no-till was more common in the project, but it had a lower average emissions reduction of 0.38 tCO2e per hectare per year. Effect sizes for no-till vary spatiotemporally and are typically low in the first several years after adoption but increase in subsequent years. Agricultural carbon programs that capture and incentivize the nuance of outcomes of practices rather than the implementation of practices, can promote adoption of the right management practice to be deployed on the right field for maximum environmental benefit.

The hepatoprotective potential of nigella sativa oil against cypermethrin-induced hepatotoxicity in rats: A histomorphological investigation.

Objective: To determine the hepatotoxic effects induced by cypermethrin. The study also attempts to evaluate the hepatoprotective efficacy of Nigella sativa oil against hepatotoxicity produced by cypermethrin. Study Design: Experimental study. Setting: Department of Anatomy, Pharmacology, and Pathology of Peshawar Medical College and Animal house of PCSIR Laboratories Complex, Peshawar. Period: May 2023 to Dec 2023. Methods: Animals were divided into two groups: Control (Group A) and Experimental (Group B). The Experimental group (Group B) is divided into two subgroups Group B-I and Group B-II. Forty-two male Sprague Dawley rats were randomly assigned to three groups of fourteen rats each in order to conduct an experimental investigation. Group A served as a control group. Cypermethrin (5.5mg/kg‾¹ body weight) per day dissolved in corn oil was administered orally to Group B-I. Cypermethrin (5.5 mg/kg‾¹ body weight) per day orally and (1ml/kg‾¹ body weight) per day of Nigella sativa oil were given to group B-II. Liver obtained from these groups were fixed for histological studies under light microscopy. Liver tissues of the cypermethrin-treated animals showed leucocytic infiltration, hydropic alterations such as ballooning degeneration and focal lytic (spotty) liver necrosis. Results: After four weeks of treatment with cypermethrin demonstrated significant liver damage in group B-I animals. In group B-II Nigella sativa oil significantly reduced hepatotoxicity and induced regenerative changes. Nigella sativa oil demonstrated protection against the cypermethrin and preserved the normal histological architecture of the liver. Conclusion: Cypermethrin had a hepatotoxic potential and caused hepatotoxicity in liver, as evidenced by the histological changes in the liver tissue. However, the study also found that Nigella sativa oil showed a better hepatoprotective effect, as it was able to effectively reverse the liver damage caused by both cypermethrin.

Pulsed DPOAEs in serial measurements : Combined analysis paradigm of simultaneously occurring changes in hearing thresholds and DPOAEs.

To date, there is no consensus on how to standardize the assessment of ototoxicity in serial measurements. For the diagnosis of damage to the cochlear amplifier, measurement methods are required that have the highest possible test-retest reliability and validity for detecting persistent damage. Estimated distortion-product thresholds (LEDPT) based on short-pulse distortion-product otoacoustic emission (DPOAE) level maps use individually optimal DPOAE stimulus levels and allow reliable quantitative estimation of cochlea-related hearing loss. Hearing thresholds were estimated objectively using LEDPT and subjectively using modified Békésy tracking audiometry (LTA). Recordings were performed seven times within threemonths at 14frequencies (f2 = 1-14 kHz) in 20ears (PTA4 (0.5-4 kHz) < 20 dB HL). Reconstruction of the DPOAE growth behavior as afunction of the stimulus levels L1, L2 was performed on the basis of 21DPOAE amplitudes. Anumerical fit of anonlinear mathematical function to the three-dimensional DPOAE growth function yielded LEDPT for each stimulus frequency. For the combined analysis, probability distributions of hearing thresholds (LTA, LEDPT), DPOAE levels (LDP), and combinations thereof were determined. LTA and LEDPT each exhibited atest-retest reliability with amedian of absolute differences (AD) of 3.2 dB and 3.3 dB, respectively. Combining LEDPT, LDP, and LTA into asingle parameter yielded asignificantly smaller median AD of 2.0 dB. It is expected that an analysis paradigm based on acombination of LEDPT, suprathreshold LDP, and fine-structure-reduced LTA would achieve higher test performance (sensitivity and specificity), allowing reliable detection of pathological or regenerative changes in the outer hair cells.

Pulsed DPOAEs in serial measurements : Combined analysis paradigm of simultaneously occurring changes in hearing thresholds and DPOAEs. German version

To date, there is no consensus on how to standardize the assessment of ototoxicity in serial measurements. For the diagnosis of damage to the cochlear amplifier, measurement methods are required that have the highest possible test-retest reliability and validity for detecting persistent damage. Estimated distortion-product thresholds (LEDPT) based on short-pulse distortion-product otoacoustic emission (DPOAE) level maps use individually optimal DPOAE stimulus levels and allow reliable quantitative estimation of cochlea-related hearing loss. Hearing thresholds were estimated objectively using LEDPT and subjectively using modified Békésy tracking audiometry (LTA). Recordings were performed seven times within threemonths at 14frequencies (f2 = 1-14 kHz) in 20ears (PTA4 (0.5-4 kHz) < 20 dB HL). Reconstruction of the DPOAE growth behavior as afunction of the stimulus levels L1, L2 was performed on the basis of 21DPOAE amplitudes. Anumerical fit of anonlinear mathematical function to the three-dimensional DPOAE growth function yielded LEDPT for each stimulus frequency. For the combined analysis, probability distributions of hearing thresholds (LTA, LEDPT), DPOAE levels (LDP), and combinations thereof were determined. LTA and LEDPT each exhibited atest-retest reliability with amedian of absolute differences (AD) of 3.2 dB and 3.3 dB, respectively. Combining LEDPT, LDP, and LTA into asingle parameter yielded asignificantly smaller median AD of 2.0 dB. It is expected that an analysis paradigm based on acombination of LEDPT, suprathreshold LDP, and fine-structure-reduced LTA would achieve higher test performance (sensitivity and specificity), allowing reliable detection of pathological or regenerative changes in the outer hair cells.

Comparison of Muscle Regeneration Effects at Different Melittin Concentrations in Rabbit Atrophied Muscle.

This research aimed to explore the healing impacts of Melittin treatment on gastrocnemius muscle wasting caused by immobilization with a cast in rabbits. Twenty-four rabbits were randomly allocated to four groups. The procedures included different injections: 0.2 mL of normal saline to Group 1 (G1-NS); 4 μg/kg of Melittin to Group 2 (G2-4 μg/kg Melittin); 20 μg/kg of Melittin to Group 3 (G3-20 μg/kg Melittin); and 100 μg/kg of Melittin to Group 4 (G4-100 μg/kg Melittin). Ultrasound was used to guide the injections into the rabbits' atrophied calf muscles following two weeks of immobilization via casting. Clinical measurements, including the length of the calf, the compound muscle action potential (CMAP) of the tibial nerve, and the gastrocnemius muscle thickness, were assessed. Additionally, cross-sectional slices of gastrocnemius muscle fibers were examined, and immunohistochemistry and Western blot analyses were performed following two weeks of therapy. The mean regenerative changes, as indicated by clinical parameters, in Group 4 were significantly more pronounced than in the other groups (p < 0.05). Furthermore, the cross-sectional area of the gastrocnemius muscle fibers and immunohistochemical indicators in Group 4 exceeded those in the remaining groups (p < 0.05). Western blot analysis also showed a more significant presence of anti-inflammatory and angiogenic cytokines in Group 4 compared to the others (p < 0.05). Melittin therapy at a higher dosage can more efficiently activate regeneration in atrophied gastrocnemius muscle compared to lower doses of Melittin or normal saline.

MORPHOLOGICAL CHARACTERISTICS OF CHANGES IN THE PERIULCEROUS ZONE OF BLEEDING GASTRODUODENAL ULCERS DEPENDING ON THE DEGREE OF BLEEDING ACTIVITY ACCORDING TO FORREST

Despite the signifi cant decrease in morbidity and mortality rates due to peptic ulcer disease of the stomach and duodenum over the past few decades, complications still occur in 10-20 % of patients. Of these, bleeding is the most common complication of peptic ulcers, with an average 30-day mortality of up to 8.6 %. The aim of the study was to evaluate histological changes in the periulcerous zone of active bleeding gastroduodenal ulcers in patients with diff erent degrees of activity of gastroduodenal bleeding according to Forrest. 378 patients with chronic bleeding ulcers of the stomach and duodenum (DPK) were evaluated endoscopically according to the Forrest classifi cation. There were 231 (61.11 %) patients with Forest IA, IB, IIA, IIB, IIS who underwent endoscopic hemostasis (injection therapy or argon plasma coagulation). In 147 (38.89 %) patients, hemostasis was not performed due to the endoscopic pattern of bleeding activity according to Forrest III. A biopsy was taken from the area of periulcerous infi ltrate during endoscopic diagnosis before hemostasis on the day of hospitalization. It has been established that endoscopic bleeding stigmata have morphological features depending on the severity of destructive, infl ammatory and regenerative changes in periulcer tissues. Microscopic analysis of biopsies of periulcerous infi ltrate in bleeding gastroduodenal ulcers allows predicting the probability of recurrence of bleeding.

Histological Evaluation of Pulpal Response and Dentin Bridge Formation After Direct Pulp Capping Using Recombinant Amelogenin and Mineral Trioxide Aggregate (MTA).

The purpose of the study was to compare and histologically investigate pulpal response and dentin bridge formation after direct pulp capping using recombinant amelogenin and mineral trioxide aggregate (MTA). Recombinant amelogenin protein and MTA were used as pulp capping materials in 120 teeth from eight mongrel dogs. Dogs were sacrificed at two different evaluation times. Regenerative changes were evaluated histologically. At two weeks, in contrast to the MTA group, most of the amelogenin group showed moderately formed hard tissue formation and the pulp tissue was completely filling the entire pulp chamber. These results were statistically significant. At two months, all the samples of the amelogenin group showed complete dentin bridge formation and the pulp chamber was filled entirely with tissue-mimicking the authentic pulp in all the specimens of the amelogenin group. These results were statistically significant. In conclusion, direct pulp capping by recombinant amelogenin protein resulted in significantly better regeneration of the dentin-pulp complex than MTA.

A rare case of liver regenerative and non-neoplastic lesion resembling a well-differentiated hepatocellular carcinoma

BackgroundNodular regenerative hyperplasia (NRH) is a rare disease that presents pathologically as diffuse hepatic nodules without fibrous septa. It is believed to be caused by vasculopathy against a background of various systemic diseases, such as hematologic, autoimmune, and drug-induced diseases, with various symptoms. In spite of the recent imaging advances, various atypical cases of nodular lesions are observed in daily clinical practice. Cases that do not completely meet these criteria are referred to as -like or -similar lesions in clinical situations, making it difficult to understand their pathogenesis. We present a case in which two hepatic nodular lesions were noted and difficult to differentiate from malignancy preoperatively. The lesions were laparoscopically resected and a pathological diagnosis with non-neoplastic liver regenerative nodules resembling NRH was made.Case presentationA 49-year-old man with no alcohol or drug intake and no past medical history was identified as having liver tumors on screening examination without any symptoms. Contrast-enhanced computed tomography (CT) showed two hepatic tumors; approximately 2-cm tumors at S7 and S8. Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) revealed fat inclusions in their contents. Ethoxybenzyl (EOB) uptake was also observed during the hepatobiliary phase. Based on preoperative examinations, we suspected well-differentiated hepatocellular carcinoma (HCC) and performed laparoscopic S7/8 partial resection for these lesions. Macroscopically, the resected specimens showed a non-cirrhotic yellowish-cut surface containing brownish, ill-defined lesions with irregular borders. Microscopically, these lesions showed zonal necrosis, congestion, and aggregation of hemosiderin-laden macrophages around the central vein. In these areas, the fatty deposition of hepatocytes was lower than that in the surrounding background hepatocytes. Histopathologically, neither neoplastic nor hyperplastic lesions were observed, and he was diagnosed as regenerative hepatic change with centrilobular necrosis.ConclusionsConsidering the pathological results, these lesions were thought to be a type of NRH-like lesion with possible hepatic vessel disorder. However, the lesion’s cause and classification was difficult to determine. The accumulation of these regenerative changes accompanying fatty liver is needed to clarify the mechanism and its clinical significance.

Morphofunctional Characteristics of Dorsal Root Ganglion Neurons in the Dynamics of Healing of a Purulent Wound

Abstract. between the morphological and functional state of spinal ganglia neurons and the dynamics of healing of a purulent wound in an experimental animal during its natural course and complex therapy with hydropulse sanitation (HIS) and the addition of platelet-rich blood plasma (PRP). Material and methods. In an experiment on 100 white outbred rats, a purulent wound on the lateral surface of the thigh was modeled by introducing a daily culture of Staphyllococcus aureus. Two groups were formed: natural healing and healing after therapy with hydropulse sanitation of the wound with an isotonic NaCl solution followed by the addition of platelet-enriched autoplasma. The material for the study was taken on the 1st, 3rd, 5th, 7th, 14th, and 21st days. The area of the wound and the dynamics of its healing were assessed using the planimetric method. For the study, lumbar spinal ganglia (SG) of segments LIII–LV. were taken. At the light-optical level, after staining with cresyl violet according to Nissl and azure B according to the S. Shea method, the area of nerve cells was measured, photometry of RNA content was carried out, and the number of satellite gliocytes was counted. The obtained data were processed using statistical analysis methods. Results. The healing process of a purulent skin wound ended with the formation of a scar on days 7–14 for both experimental groups. The use of GIS and PRP demonstrated better dynamics of defect closure - a reduction in wound area by 59.35±3.4% (p=0.018) in the period from 3 to 5 days, compared with 40.05±2.9% (p=0.009) with natural healing. The response of SG neurons during healing was characterized by pronounced polymorphism. The maximum number of cells with reactive changes during natural healing was observed on the 5th day of the experiment (17.2±3.2% for A-neurons and 36.7±4.3% for B-neurons). Complex therapy led to a decrease in the proportion of both reactively altered and destructive neurons. The cell area, RNA content, and the number of satellite glia increased on average by the 7th day of the experiment. Separate close correlations were identified between the dynamics of changes in the wound area and the studied quantitative characteristics. Conclusion. A purulent wound causes a complex of nonspecific reactions in the neurons of the SG. In the dynamics of wound healing, neurons with reactive changes more often demonstrated biphasic dynamics, more pronounced for B-type cells with a primary reaction on days 1–3 and a further transition to regenerative hypertrophy or destruction. Regenerative changes in SG neurons had a close correlation with the processes of regeneration of the wound defect.

Assessment of Protective Roles of Aqueous Seed Extract of Sour-Sop (Annona muricata) in Cerebellum Following Cadmium-induced Neurotoxicity of Adult Wistar Rats

Cadmium, a deleterious heavy metal that pervades the environment, has the potential to accumulate in the body and cause health complications. In the domain of traditional medicine, medicinal plants have been employed to combat the toxicity of heavy metals and treating of many diseases in traditional medicine.&#x0D; Aim: To access the protective impact of Annona muricata seed extract on cadmium-triggered neurotoxicity in the cerebellum of albino wistarrat.&#x0D; Place of Study: Department of Anatomy, Faculty of Basic Medical Sciences Olabisi Onabanjo University, Ogun State between June 2022 and June 2023&#x0D; METHODOLOGY: After a period of 14 days of acclimatization, 40 healthy male wistar rats were randomly allocated to four groups, group1(2ml/kg of distilled water), group2 cadmium only(2g/kg SC), group3 (2g/kg cadmium + 100mg/kg extract of Annona muricata) and group4(2g/kg cadmium + 200mg/kg extract of Annona muricata) The rats were subjected to cadmium subcutaneously followed by the oral administration of aqueous seed extract of Annona Muricata for fifteen consecutive days.&#x0D; Results: The impact of the extract on antioxidant enzymes activities of the cerebellum, cerebellar weight, as well as the histology of the cerebellum were scrutinized. The data revealed that the aqueous seed extract of Annona muricata, in a dose-dependent manner, augmented the levels of superoxide dismutase (SOD) (P=0.005) and catalase (CAT) (P=0.027) in contrast to the cadmium-only group. The relative weight of the cerebellum exhibited a significant increasein the treated groups compared to the cadmium-only group.&#x0D; The histology of the cerebellum delineated pathological changes arising from the exposure to cadmium, while Annona muricata brought about regenerative changes.&#x0D; Conclusion: In summary, the study posits that owing to the presence of phytochemicals in Annona muricata aqueous seed extract, it was efficacious in mitigating the neurotoxicity induced by cadmium in the cerebellum of male rats.

Toxic effects of nickel on tolerance and regeneration in the freshwater shrimp Neocaridina davidi

Heavy metals cause environmental pollution and produce toxic effects on organisms. Nickel (Ni) is a common metallic pollutant of aquatic ecosystems and potentially can produce multifarious changes in the body of aquatic organisms. The average nickel content in rivers is about 0.7 μg/l. As a result, the homeostasis of the affected organism is disturbed, and processes that can counteract the changes are activated. To better understand the effects of Ni in the freshwater environment and its fauna, it is important to establish whether all changes caused in cells and tissues by Ni exposure are reversible when the animal returns to the non-polluted environment. Thus, the main aim of the study was to analyze changes that occur after Ni exposure and after it is returned to non-contaminated water at various levels of the animal’s body. The freshwater shrimp Neocaridina davidi (Crustacea) was selected as the subject of the study. As the organ for studies, we chose the midgut because it is a barrier against stressors that enter the organism. A concentration of 3.63 mg Ni/l was selected for the experiment, at which approximately 50% mortality of the population was observed after 14 days. The midgut was analyzed using light and transmission electron microscopy (TEM), confocal microscopy, and flow cytometry for qualitative and quantitative results. When the organisms were transferred to clean water, a prolong exposure resulted in a decrease in the values of the analyzed parameters (e.g. ROS, cell death, etc.) proportional to the purification time. The recovery time was insufficient to return to control values in most analyzed groups. Nevertheless, the occurrence of regenerative changes suggests that freshwater shrimps are relatively tolerant to nickel, when the exposure time is short and the recovery time is long.

Future Liver Remnant Regeneration Post Hepatectomy: Histologic Changes in an Animal Model

Background: The liver possesses remarkable regenerative abilities following parenchymal injury. This study aimed to assess and document the microscopic regenerative changes in the rat liver using a partial hepatectomy model. Methodology: Adult male Sprague Dawley rats weighing approximately 200-300 grams were subjected to partial hepatectomy, leaving approximately 70% future liver remnant. The rats were euthanized at designated time intervals (1/2 hour, 48 hours, 72 hours, 7 days, 11 days, and 14 days) for histological analysis of the liver. Results: Liver regeneration was observed within 1 week of partial hepatectomy. Cytoplasmic vacuolization increased until day 7, but decreased significantly during the regenerative process. Disruption of cytoplasmic membranes and blurring of cell-to-cell and cell-to-sinusoidal space boundaries decreased notably from day 11. Necrosis involving central veins and portal tracts was observed on the first day after hepatectomy. By day 7, the portal tract exhibited granulomatous inflammation with conglomerates of epithelioid macrophages forming giant cells. The sinusoidal spaces displayed increased lymphocyte volume on day 7. Patchy portal inflammation consisting of lymphocytes, plasma cells, occasional eosinophils, and monocytes was observed from day 7 post-hepatectomy. Conclusion: In this partial hepatectomy animal model, the inflammatory cascade was evident through confluent necrosis affecting approximately 10% of the hepatic parenchyma, along with subcapsular infarction. Cytoplasmic vacuolization affected approximately 50% of the cells. The study documented various histological changes during the post-hepatectomy period, demonstrating the initiation of hepatocyte regeneration within one week.

Portal hypertension in common variable immunodeficiency disorders - a single center analysis on clinical and immunological parameter in 196 patients.

Liver manifestations and in particular portal hypertension (PH) contribute significantly to morbidity and mortality of patients with common variable immunodeficiency disorders (CVID). Screening strategies and early detection are limited due to the lack of specific diagnostic tools. We evaluated clinical, immunological, histological, and imaging parameters in CVID patients with clinical manifestation of portal hypertension (CVID+PH). Portal hypertension was present in 5.6% of CVID patients and was associated with high clinical burden and increased mortality (18%). Longitudinal data on clinical and immunological parameters in patients before and during clinically manifest portal hypertension revealed a growing splenomegaly and increasing gamma-glutamyl transferase (GGT) and soluble interleukin 2 receptor (SIL-2R) levels with decreasing platelets over time. While ultrasound of the liver failed to detect signs of portal hypertension in most affected patients, transient elastography was elevated in all patients. All CVID+PH patients had reduced naïve CD45RA+CD4+ T-cells (mean of 6,2%). The frequency of severe B-lymphocytopenia (Euroclass B-) was higher in CVID+PH patients. The main histological findings included lymphocytic infiltration, nodular regenerative hyperplasia-like changes (NRH-LC), and porto(-septal) fibrosis. CVID patients with lower naïve CD45RA+CD4+ T-cells or severely reduced B-cells might be at higher risk for portal hypertension. The combination of biochemical (increasing sIL-2R, GGT, and decreasing platelets) and imaging parameters (increasing splenomegaly) should raise suspicion of the beginning of portal hypertension.

Bone Marrow Mobilization and Local Stromal Cell-Derived Factor-1α Delivery Enhances Nascent Supraspinatus Muscle Fiber Growth.

Rotator cuff tear is a significant problem that leads to poor clinical outcomes due to muscle degeneration after injury. The objective of this study was to synergistically increase the number of proregenerative cells recruited to injure rotator cuff muscle through a novel dual treatment system, consisting of a bone marrow mobilizing agent (VPC01091), hypothesized to "push" prohealing cells into the blood, and localized delivery of stromal cell-derived factor-1α (SDF-1α), to "pull" the cells to the injury site. Immediately after rotator cuff tendon injury in rat, the mobilizing agent was delivered systemically, and SDF-1α-loaded heparin-based microparticles were injected into the supraspinatus muscle. Regenerative and degenerative changes to supraspinatus muscle and the presence of inflammatory/immune cells, mesenchymal stem cells (MSCs), and satellite cells were assessed via flow cytometry and histology for up to 21 days. After dual treatment, significantly more MSCs (31.9 ± 8.0% single cells) and T lymphocytes (6.7 ± 4.3 per 20 × field of view) were observed in supraspinatus muscle 7 days after injury and treatment compared to injury alone (14.4 ± 6.5% single cells, 1.2 ± 0.7 per 20 × field of view), in addition to an elevated M2:M1 macrophage ratio (3.0 ± 0.5), an indicator of a proregenerative environment. These proregenerative cellular changes were accompanied by increased nascent fiber formation (indicated by embryonic myosin heavy chain staining) at day 7 compared to SDF-1α treatment alone, suggesting that this method may be a promising strategy to influence the early cellular response in muscle and promote a proregenerative microenvironment to increase muscle healing after severe rotator cuff tear.

Hepato-Protective Activities of Ethanol Extracts of African Eggplant and Bitter Leaf in Alloxan Induced Diabetic Rats

Diabetes is a metabolic disorder, which affect all system of the body including the liver. This study focused on the effect of the ethanol extract of African eggplant and bitter leaf and their combination on the liver structure, antioxidant enzymes activities and biochemical parameters in the liver of alloxan induced diabetic rats. Twenty-five male wistar rats were grouped into normal control group A, diabetic control group B, 100 mg/kg African eggplant extract treated group C, 100 mg/kg bitter leaf extract treated group D and combination of 100 mg/kg of African eggplant and 100 mg/kg bitter leaf treated group E. The results study showed that group E rats showed significant reduction in the activity of AST, ALP and AST. In the antioxidant enzyme activity, the administered extracts increased the antioxidant enzyme activities and reduced lipid peroxidation, thereby protecting the cells from oxidative stress. The micro- histo-architecture of the liver showed improvement and regenerative changes across the treated groups. The study reveal that combination of the ethanol leaf extract of bitter leaf and African eggplant can manage liver malfunction caused by diabetes.

Antioxidants with proven efficacy and elastin-conserving vitamin C-A new approach to free radical defense.

This paper describes the background research and validation related to the formulation of a novel antioxidant product. Two defined outcomes were sought. Firstly, a combined efficacy of antioxidant ingredients in quenching free oxygen radicals. Secondly, the investigation into whether a vitamin C derivative sodium salt was elastin conserving in contrast to current vitamin C/l-ascorbic acid variations that have been reported to negatively affect elastin constitution and regeneration. A leading l-ascorbic acid antioxidant available on the market was compared with the experimental new product in two studies. In the first experiment, the products were compared to assess their antioxidant properties. The evaluated products TOPICAL ANTIOXIDANT 1 and TOPICAL ANTIOXIDANT 2 were applied to human skin cultures (25-30 mg/cm2 ) for a total of 72 h of treatment and exposed to oxidative stress. The generation of free radicals was semi-quantitatively assessed by measuring the fluorescence intensity of the deacetylation and oxidation of the probe dichlorofluorescein diacetate (DCFH-DA). In the second experiment, an ex vivo skin model (derived from patients undergoing facelift procedures) was used to assess elastin preservation. Three skin explants were topically subjected to the two formulations daily for 7 days. The skin was then prepared and fixed for immunofluorescent assessment after staining with CD44 and tropoelastin antibodies. Images were then analyzed using ImageJ. A full description of the different components selected for the new formulation is presented. In the first study, the experimental formulation performed with absolute equivalence to the comparator in its radical quenching capacity; both showed extremely effective antioxidant function. In the second study, the comparator negatively affected the existing elastin with areas of breakdown and diminished staining. In contrast, the new formulation showed good conservation of healthy elastin in all sections demonstrating elastin preservation. A new antioxidant formulation was carefully designed with multiple actives that show an equivalent antioxidant capacity to a leading product on the market. More importantly, the vitamin C component shows direct elastin conservation and improvement as opposed to the comparator, which had negative effects on elastin preservation. This is in keeping with little-known literature reports on vitamin C and its negative effects on elastin and validates the use of a sodium salt derivative, which appears to have protective effects on elastin. These findings support the overall regenerative extracellular matrix changes seen with TriHex® technology in other products.

Multiple cryosauna sessions for post-exercise recovery of delayed onset muscle soreness (DOMS): a randomized control trial.

The main goal was to investigate the effectiveness of cryosauna in preventing the development of delayed onset muscle soreness and to analyze the regenerative changes within muscles after acute fatigue-induced exercises. Thirty-one volunteers were assigned into two groups: 1) an intervention group that participated in cryostimulation after fatigue-induced exercise protocol (CRYO, n = 16) and a control group that performed fatigue-induced exercise protocol, but without any intervention (CONT, n = 15). Main outcome measures include at baseline: blood sample testing (leukocyte content, myoglobin concentration, and creatine kinase activity) and muscle stiffness of lower extremity; immediately after (stiffness), and 24-48-72-96h post-exercise (blood samples and stiffness). Both groups performed an exercise-induced muscle damage protocol based on repeated countermovement jumps (10 sets, 10 repetitions). The CRYO group underwent a cryosauna (temperature: -110°C, time: 1.5min per session) intervention during four sessions (i.e., immediately after, 24-48-72h post-exercise). Leukocyte content was significantly greater 24-48-72h after exercise in CONT, compared with the CRYO group (p ≤ 0.05 for all), while creatine kinase activity was greater 24-48-96h in CONT, compared with the CRYO group (p ≤ 0.05 for all). Muscle stiffness increased significantly in rectus femoris, tibialis anterior, and fibula muscle after 48h post-exercise (p ≤ 0.05 for all), as well as in tibialis anterior and fibula after 72h post-exercise (p ≤ 0.05 for all) in the CRYO group. Multiple cryosauna was an effective recovery strategy that reduced blood biomarkers and muscle stiffness after exercise-induced muscle damage. Moreover, the development of delayed onset muscle soreness, expressed by a greater muscle stiffness post-exercise, was attenuated to the first 48h.

Capecitabine-induced Gastrointestinal Injury Shows a Graft-Versus-Host Disease (GVHD)-like Pattern.

Capecitabine is a commonly used oral chemotherapeutic agent. Gastrointestinal (GI) side effects are clinically well-known, however, the histopathologic changes have not been comprehensively studied. This study describes the largest case series (8 patients) characterizing the histopathology of capecitabine-induced GI injury. All patients were adults (median age: 64.5y, range: 61 to 76y) and there was gender parity. Patients were receiving treatment for malignancies of the colorectum (n=5), breast (n=1), pancreas (n=1), and appendix (n=1). All had GI symptoms, including 7 with diarrhea and abdominal pain and 1 with melena. Five of 8 (63%) showed graft-versus-host disease (GVHD)-like histologic changes in small intestinal and/or colonic biopsies characterized by crypt disarray and dropout, crypt atrophy, dilated crypts lined by attenuated epithelium, and increased crypt apoptosis. Neuroendocrine cell aggregates were present in 4 of 5 cases. Four of 5 showed patchy prominence in lamina propria eosinophils. One patient receiving concomitant radiation therapy had a small intestinal biopsy showing regenerative changes. Two patients had histologically unremarkable biopsies. On follow-up, capecitabine was discontinued or dose-reduced in all patients. Three of 5 patients with a GVHD-like pattern had clinical improvement, whereas 2 died shortly after biopsy. One with regenerative changes also had radiation dose reduction and improved clinically. Two with unremarkable biopsies improved symptomatically. In summary, capecitabine-related GI injury shows a GVHD-like pattern. Knowledge of this is important to confirm the diagnosis as patients typically improve with dose reduction or discontinuation of the drug.

Bee Honey Extract Attenuates Hyperglycemia in Induced Type 1 Diabetes: Impact of Antioxidant and Angiogenesis Activities on Diabetic Severity In Vivo

Background: Diabetes mellitus (DM) has become a disease prevalent worldwide. Honey, which comprises predominantly bioactive constituents, has anti-inflammatory, antioxidant, and immunomodulating properties. Aim: Recent developments and benefits of natural products in treating various diseases have caught the attention of researchers. This study aims to investigate the antidiabetic effect of bee honey extract on induced diabetic Swiss mice. Materials and Methods: Fifty Swiss male mice were randomly assigned to five groups of 10 mice each. Group I served as the negative control; in group II, the mice received 2 mg/kg/b.wt of honey extract only; and groups III, IV, and V received cyclosporine (CsA) (20 mg/kg/day, s.c.) daily for 10 days prior to receiving streptozotocin (STZ) inoculated at multiple low doses (MLDSTZ) (30 mg/kg/day, i.p.) for five consecutive days. Group IV was administered with insulin initiated at a dose of 0.5 U/kg/b.wt as a standard treatment (positive control). Group V was administered 2 mg/kg/b.wt of honey extract, while group III received no treatment. Results: The results showed a significant hypoglycemic effect, increased body weight, increased liver glycogen levels, and the amelioration of antioxidant activities in groups IV and V compared with the diabetic group III. Moreover, serum matrix metalloproteinase (MMP-9) concentrations were significantly reduced in the mice treated with the insulin and honey extract in groups IV and V and the tissue inhibitor metalloproteinase-1 (TIMP-1) levels were significantly higher than the serum levels in group III. Furthermore, the histopathological examination of groups IV and V revealed regenerative changes with the restoration of normal islet cell architecture, as compared to the diabetic mice in group III. Compared to group I, group II showed no changes and exhibited non-significant data. Conclusion: Honey extract plays an effective role in improving all biomarkers in treated group V. Furthermore, MMP-9 and TIMP-1 are considered prognostic markers in the progression, severity, diagnosis, and treatment of type 1 DM. This may play an important role for the treatment of individuals in the future.