Microscopic Scores Research Articles

Immunohistochemical Evaluation of Histamine Levels and Hygienic Aspect of Little Tunny (Euthynnus alletteratus) Musculature at Different Environment Time and Temperature

ABSTRACT We investigated the effect of storage time and temperature on muscular histamine (HIS) contents in little tunny (LT). Fifty LT were preserved at various temperatures (0- 21°C). We collected muscles from several areas at 0-, 6-, 12-, 18-, and 24 h post-fishing for further examination. Throughout storage time and temperature, there was a significant increase in fish deterioration, HIS levels, and HFB count in abdominal > tail > dorsal muscle. Vitek2 gave 99% confidence identity of the highly histaminergic strains Lelliottia amnigena-1 and Acinetobacter haemolyticus. There was a positive correlation between HIS levels, HFB counts, and microscopic lesion scores during storage.

Lactoferrin improves symptoms of dextran sulfate sodium-induced colitis in mice through modulation of cellular senescence

The multifaceted effects of lactoferrin (LF) on the digestive and immune systems make it an attractive therapeutic option in inflammatory bowel diseases. In this study, we aimed to explore the anti-inflammatory effects of LF in colitis, particularly in relation to cellular senescence. We hypothesize that LF has the potential to modulate the senescence process. The effects of LF on senescence were tested in vitro using HCT116 and SW480 cell lines, and in vivo, the dextran sulfate sodium–induced mouse model of colitis. LF (500 mg/kg) alleviated symptoms of colitis in mice with a significant decrease in colon damage (P < .0001 vs. control) and microscopic (P < .05 vs. control) scores. Cellular senescence markers p16 and p21 were significantly upregulated in the mouse colon during inflammation (both P < .01 vs. control), and LF at 500 mg/kg decreased these markers (both P < .05 vs. dextran sulfate sodium–treated mice). In vitro, LF significantly affected the expression of p16 and p21 (P < .05–P < .0001 vs. control), senescence associated secretory phenotype (P < .01–P < .0001 vs. control), and telomere-specific proteins: telomeric repeat binding factor 1 and 2 (P < .05–P < .0001 vs. control) in a concentration-dependent manner. LF modulates the expression of cellular senescence markers and shows hallmarks of senolytic and pro-senescent activity, depending on dose. Further studies are needed to fully understand the anti-inflammatory effect of LF in the context of senescence and safe utilization in patients with inflammatory bowel diseases.

Huang-Qi-Jian-Zhong-Tang accelerates healing of indomethacin-induced gastric ulceration in rats via anti-inflammatory and antioxidant mechanisms

Ethnopharmacological relevanceHuang-Qi-Jian-Zhong-Tang (HQJZT) is a canonical traditional Chinese medicine (TCM) formula that has been widely used in both the prevention and treatment of gastrointestinal diseases, including gastric ulcer, duodenal ulcer, and chronic atrophic gastritis, in China. Aim of the studyIn the present study, we investigated the gastroprotective potential of HQJZT in a rat model of indomethacin (IND)-induced gastric ulcer and explained the biochemical, cellular, and molecular mechanisms involved. Materials and methodsObservations were conducted at the macroscopic level to ascertain the ulcer index (UI) and the curative index (CI). Histopathological examinations were conducted, and a microscopic score (MS) was computed. The gastric juice volume, total acidity, pH value, and pepsin activity were quantified. Antioxidant and oxidative parameters were assessed, namely GSH, CAT, SOD, and MDA content. The RFLSI Pro instrument was employed to measure the blood flow within the gastric mucosa continuously. The mRNA levels of the inflammatory cytokines were assessed using droplet digital PCR (ddPCR). Molecular docking was employed to examine the interaction between representative active components of HQJZT and the binding sites associated with the NF-κB and STAT signaling pathways. The protein expression and localization of p-JAK, p-STAT, p-IκBβ, and p–NF–κB were evaluated through immunofluorescence analysis. ResultsThe administration of HQJZT treatment demonstrated a significant reduction in gastric lesions induced by IND, leading to a notable decrease in the UI. Additionally, HQJZT treatment significantly decreased gastric juice volume, acidity, and pepsin activity, accompanied by increased pH value. IND-treated stomachs exhibited severe hemorrhagic necrosis, submucosal edema, and epithelial cell destruction. However, the administration of HQJZT effectively counteracted these pathological changes. Furthermore, HQJZT administration significantly increased blood flow to the gastric mucosa. HQJZT enhanced antioxidant defenses and modulated oxidative stress by increasing SOD, CAT, and GSH activities while reducing MDA levels. Moreover, HQJZT reversed IND-induced increases in mRNA expression levels of inflammatory cytokines. Molecular docking analysis revealed that the representative active components of HQJZT could bind to the NF-κB and STAT signaling pathways. In addition, immunofluorescence microscopy revealed that HQJZT markedly attenuated the phosphorylation of IκΒβ, NF-κB, JAK, and STAT. ConclusionsThe therapeutic and protective effect of HQJZT on gastric ulcers is attributed to its ability to suppress gastric acid secretion, enhance antioxidative defenses and blood flow, mitigate proinflammatory cytokines, and inhibit the activation of NF-κB and STAT signaling pathways.

The influence of cognitive ability in Chinese reading comprehension: can working memory updating change Chinese primary school students' reading comprehension performance?

With the development of educational cognitive neuroscience, language instruction is no longer perceived as mechanical teaching and learning. Individual cognitive proficiency has been found to play a crucial role in language acquisition, particularly in the realm of reading comprehension. The primary objective of this study was to investigate two key aspects: firstly, to assess the predictive effects of the central executive (CE) on the Chinese reading comprehension scores of Chinese primary school students, and secondly, to explore the influence of CE training on the Chinese reading comprehension performance of Chinese primary school students. Chinese primary school students were recruited as participants. Experiment 1 used a Chinese N-back task, a Chinese Stroop task, and a number-pinyin conversion task to investigate the predictive effect of the CE components on Chinese reading comprehension. Experiment 2, based on the results of Experiment 1, used the Chinese character N-back training to explore the influence of updating training on Chinese reading comprehension. The findings from Experiment 1 underscored that CE had a predictive effect on Chinese reading comprehension scores. And updating had a prominent role in it. Experiment 2 revealed that the experimental group exhibited an enhancement in their updating performance following N-back training. Although the reading comprehension performance of the two groups after training did not produce significant differences in total scores, the experimental group showed maintained and higher microscopic reading comprehension scores than the control group in the more difficult post-test. In summary, this study yields two primary conclusions: (1) CE was able to predict Chinese reading comprehension scores. Updating has an important role in prediction. (2) Updating training enhances students' updating performance and positively influences students' Chinese microscopic reading comprehension performance.

Three-Dimensional Imaging and Histopathological Features of Third Metacarpal/Tarsal Parasagittal Groove and Proximal Phalanx Sagittal Groove Fissures in Thoroughbred Horses.

Fissure in the third metacarpal/tarsal parasagittal groove and proximal phalanx sagittal groove is a potential prodromal pathology of fracture; therefore, early identification and characterisation of fissures using non-invasive imaging could be of clinical value. Thirty-three equine cadaver limbs underwent standing cone-beam (CB) computed tomography (CT), fan-beam (FB) CT, low-field magnetic resonance imaging (MRI), and macro/histo-pathological examination. Imaging diagnoses of fissures were compared to microscopic examination. Imaging features of fissures were described. Histopathological findings were scored and compared between locations with and without fissures on CT. Microscopic examination identified 114/291 locations with fissures. The diagnostic sensitivity and specificity were 88.5% and 61.3% for CBCT, 84.1% and 72.3% for FBCT, and 43.6% and 85.2% for MRI. Four types of imaging features of fissures were characterised on CT: (1) CBCT/FBCT hypoattenuating linear defects, (2) CBCT/FBCT striated hypoattenuated lines, (3) CBCT/FBCT subchondral irregularity, and (4) CBCT striated hypoattenuating lines and FBCT subchondral irregularity. Fissures on MRI appeared as subchondral bone hypo-/hyperintense defects. Microscopic scores of subchondral bone sclerosis, microcracks, and collapse were significantly higher in locations with CT-identified fissures. All imaging modalities were able to identify fissures. Fissures identified on CT were associated with histopathology of fatigue injuries.

Locally Advanced Adrenocortical Carcinoma in Children and Adolescents-Enigmatic and Challenging Cases.

Locally advanced tumors account for approximately 50% of children and adolescents with adrenocortical carcinoma (ACC), and of these, up to 50% relapse. We explored the five-item microscopic score and the pS-GRAS score for guiding management. Data from children and adolescents with COG stage II and III ACC registered in the MET studies were included. The five-item and pS-GRAS score were retrospectively calculated. By December 2021, 55 patients with stage II and III (stage II n = 18, stage III n = 37) had been reported. Median age was 4.3 years [0.1-17.8], median duration of follow-up 6.0 years [0-16.7]. 3-year event-free survival (EFS) rate was 76.5% and 49.8% (p = 0.088), respectively. In stage II tumors, neither the five-item score (p = 0.872) nor pS-GRAS grouping (p = 0.218) had any effect as prognostic factors. In stage III patients, EFS was impaired in tumors with unfavorable histology according to the five-item score (100% vs. 30.8%, p = 0.018). No difference was observed for pS-GRAS groups (p = 0.798). In patients with COG stage III, but not stage II, the five-item score affected EFS. Further studies are needed to identify patients at risk in COG stage II.

Pathogenesis of an experimental coinfection of porcine parainfluenza virus 1 and influenza A virus in commercial nursery swine

Porcine parainfluenza virus 1 (PPIV-1) is a recently characterized swine respirovirus. Previous experimental studies reported PPIV-1 replicates in the porcine respiratory tract causing minimal clinical disease or lesions. However, it is unknown if PPIV-1 co-infections with viral respiratory pathogens would cause respiratory disease consistent with natural infections reported in the field. The objective of this study was to evaluate if PPIV-1 increases the severity of influenza A virus respiratory disease in swine. Fifty conventional, five-week-old pigs were assigned to one of three challenge groups (n = 15) or a negative control group (n = 5). Pigs were challenged with a γ-cluster H1N2 influenza A virus in swine (IAV-S; A/Swine/North Carolina/00169/2006), PPIV-1 (USA/MN25890NS/2016), inoculum that contained equivalent titers of IAV-S and PPIV-1 (CO-IN), or negative control. Clinical scores representing respiratory disease and nasal swabs were collected daily and all pigs were necropsied five days post inoculation (DPI). The CO-IN group demonstrated a significantly lower percentage of pigs showing respiratory clinical signs relative to the IAV-S challenge group from 2 to 4 DPI. The IAV-S and CO-IN groups had significantly lower microscopic composite lesion scores in the upper respiratory tract compared to the PPIV-1 group although the IAV-S and CO-IN groups had significantly higher microscopic composite lung lesion scores. Collectively, PPIV-1 did not appear to influence severity of clinical disease, macroscopic lesions, or alter viral loads detected in nasal swabs or necropsy tissues when administered as a coinfection with IAV-S. Studies evaluating PPIV-1 coinfections with different strains of IAV-S, different respiratory pathogens or sequential exposure of PPIV-1 and IAV-S are warranted.

Intra-articular injection of secretome, derived from umbilical cord mesenchymal stem cell, enhances the regeneration process of cartilage in early-stage osteo-arthritis: an animal study.

Mesenchymal stem cells (MSCs), both endogenous and exogenous, enhance chondrocyte proliferation by stimulating collagen type II. Secretome, an MSC derivate, has shown to also provide this mechanism through a paracrine effect. We aimed to evaluate the use of secretome and MSC in the management of early osteoarthritis (OA). 19 (1 control) male sheep (Ovies aries), which were operated on with total lateral meniscectomy to induce knee OA, were divided into 3 groups: the secretome group, hyaluronic acid group, and MSC group. Each group was injected with the respective substances and was evaluated macroscopically and microscopically. The Osteoarthritis Research Society International (OARSI) score was calculated for all subjects and a descriptive and comparative statistical analysis was undertaken. The macroscopic analysis of the treated groups revealed better OARSI score in the secretome group compared with the other 2 groups. The secretome group showed a significantly better microscopic score compared with the hyaluronic acid group (mean difference [MD] 6.0, 95% confidence interval [CI] 0.15-12), but no significant difference compared with the MSC group (MD 1.0, CI -4.8 to 6.8). Intra-articular injection of secretome is effective in managing early-stage osteoarthritis in the animal model compared with hyaluronic acid and has similar efficacy to MSC injection.

The impact of the experimental route of challenge on the host responses and pathogenesis of the Canadian Delmarva (DMV/1639) infectious bronchitis virus infection in laying chickens

Infectious bronchitis virus (IBV) infection can be associated with respiratory, renal, and/or reproductive diseases in chickens. Under natural conditions, conjunctiva, mucosa of upper respiratory tract, and cloaca are the main routes of IBV entry. Experimentally, the study of IBV infection involved various routes of inoculation. This study investigated the impact of adding the trachea as a potential route of viral entry to the oculo-nasal infection on the host responses, pathogenicity, and tissue tropism of the Canadian IBV Delmarva (DMV/1639) strain in laying chickens. Specific-pathogen-free laying chickens were divided into three experimental groups: control group (Con group), oculo-nasal challenged group (ON group), and oculo-nasal/intratracheal challenged group (ON/IT group); all groups were observed for 12 days post-infection (dpi). The clinical signs and reduction in egg production in the ON/IT group started slightly earlier compared to the ON group. At 12 dpi, the gross lesions in the ON/IT group were confined to the ovary, while the ON group showed regressed ovary and atrophied oviduct. Only the ON group showed significantly higher microscopic lesion scores in the lung, kidney, magnum, and uterus compared to the control group at 12 dpi. The oviduct tissues of the ON group showed a significant increase in B cells infiltration compared to ON/IT and control groups. The viral shedding (detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR)), tissue tropism (detected either by qRT-PCR or immunohistochemistry (IHC)), T/natural killer cells infiltration in reproductive tract (detected by IHC), and antibody-mediated immune responses (measured by enzyme-linked immunosorbent assay) showed similar patterns in the ON and ON/IT groups.

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

Hemophilic arthropathy can cause recurrent hemarthroses and severe damage to the synovium and articular cartilage. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an essential role in neoangiogenesis. Bevacizumab, a monoclonal VEGF inhibitor, is used clinically to prevent angiogenesis. However, its effects on hemophilic arthropathy are unknown. Using a hemophilic arthropathy rabbit model, we asked: Does an intra-articular injection of bevacizumab (1) inhibit VEGF, (2) decrease signal intensity in dynamic contrast-enhanced MRI (DCE-MRI) as an assessment of capillary permeability and neoangiogenesis, (3) reduce cartilage damage, (4) reduce synovial changes, and (5) affect macroscopic changes during the development of hemophilic arthropathy? Twenty-five male New Zealand rabbits were divided into four groups. Eight knees from four rabbits were used as the control group. We used an established animal model for hemophilic arthropathy in the remaining 21 rabbits. Animals were assigned randomly to three groups with seven rabbits in each group. One group was used to establish mild arthropathy, and the other two were used to establish severe arthropathy. Autologous blood from the rabbits' ears was injected into the right and left knees twice per week for 8 weeks to represent mild arthropathy and for 16 weeks to represent severe arthropathy. In the mild arthropathy group, bevacizumab was injected into the right knee once every 2 weeks. Bevacizumab was injected into the right knee of rabbits in one of the severe arthropathy groups once every 2 weeks for 16 weeks, and intra-articular bevacizumab injections were administered to the right knees of rabbits in the other severe arthropathy group once every 2 weeks after the eighth week. An equal volume of 0.9% saline was injected into the left knee of rabbits in all arthropathy groups. To explore the efficacy of bevacizumab, joint diameters were quantitatively measured, and cartilage and synovial changes were examined. Degeneration of articular cartilage was evaluated with the semiquantitative Osteoarthritis Research Society International grading system. Synovial damage was analyzed with a semiquantitative microscopic scoring system. In addition, we evaluated perfusion and angiogenesis using DCE-MRI (quantitative signal intensity changes). Immunohistochemical testing was used to measure VEGF levels (analyzed by Western blotting). Intra-articular bevacizumab treatment inhibited VEGF in our rabbit model of hemophilic arthropathy. VEGF protein expression levels were lower in the mild arthropathy group that received intra-articular bevacizumab (0.89 ± 0.45) than the mild arthropathy control group (1.41 ± 0.61) (mean difference -0.52 [95% CI -0.898 to -0.143]; p = 0.02). VEGF levels were lower in the severe arthropathy group that received treatment for 16 weeks (0.94 ± 0.27) than in the control knees (1.49 ± 0.36) (mean difference -0.55 [95% CI -0.935 to -0.161]; p = 0.01). In the severe arthropathy group, the Osteoarthritis Research Society International score indicating cartilage damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than in the control group (median 17 [range 13 to 18] versus 18 [range 17 to 20]; difference of medians 1; p = 0.02). Additionally, the scores indicated synovial damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than the control group (median 5 [range 4 to 9] versus 9 [range 8 to 12]; difference of medians 4; p = 0.02). The mean of mean values for signal intensity changes was higher in the nontreated severe groups than in the group of healthy knees. The signal intensity changes were higher in the severe arthropathy control groups (Groups BC and CC) (median 311.6 [range 301.4 to 361.2] and 315.1 [range 269.7 to 460.4]) than in the mild arthropathy control group (Group AC) (median 234.1 [range 212.5 to 304.2]; difference of medians 77.5 and 81, respectively; p = 0.02 and p = 0.04, respectively). In the severe arthropathy group, discoloration caused by hemosiderin deposition in the cartilage and synovium was more pronounced than in the mild arthropathy group. In the severe arthropathy group treated with intra-articular bevacizumab, joint diameters were smaller than in the control group (Group BT median 12.7 mm [range 12.3 to 14.0] versus Group BC median 14.0 mm [range 13.1 to 14.5]; difference of medians 1.3 mm; p = 0.02). Hemarthrosis damages the synovial tissues and cartilage in the knees of rabbits, regardless of whether they are treated with intra-articular bevacizumab. However, intra-articular injection of bevacizumab may reduce cartilage and synovial damage in rabbits when treatment is initiated early during the development of hemophilic arthropathy. If the findings in this study are replicated in larger-animal models that consider the limitations of our work, then a trial in humans might be appropriate to ascertain whether intra-articular injection of bevacizumab could reduce cartilage damage and synovial changes in patients with hemophilia whose hemarthroses cannot otherwise be controlled.

A New Gold(III) Complex, TGS 703, Shows Potent Anti-Inflammatory Activity in Colitis via the Enzymatic and Non-Enzymatic Antioxidant System-An In Vitro, In Silico, and In Vivo Study.

Inflammatory bowel diseases (IBD) and their main representatives, Crohn's disease and ulcerative colitis, are worldwide health-care problems with constantly increasing frequency and still not fully understood pathogenesis. IBD treatment involves drugs such as corticosteroids, derivatives of 5-aminosalicylic acid, thiopurines, and others, with the goal to achieve and maintain remission of the disease. Nowadays, as our knowledge about IBD is continually growing, more specific and effective therapies at the molecular level are wanted. In our study, we tested novel gold complexes and their potential effect on inflammation and IBD in vitro, in silico, and in vivo. A series of new gold(III) complexes (TGS 404, 512, 701, 702, and 703) were designed and screened in the in vitro inflammation studies. In silico modeling was used to study the gold complexes' structure vs. their activity and stability. Dextran sulphate sodium (DSS)-induced mouse model of colitis was employed to characterize the anti-inflammatory activity in vivo. Lipopolysaccharide (LPS)-stimulated RAW264.7 cell experiments proved the anti-inflammatory potential of all tested complexes. Selected on the bases of in vitro and in silico analyses, TGS 703 significantly alleviated inflammation in the DSS-induced mouse model of colitis, which was confirmed by a statistically significant decrease in the macro- and microscopic score of inflammation. The mechanism of action of TGS 703 was linked to the enzymatic and non-enzymatic antioxidant systems. TGS 703 and other gold(III) complexes present anti-inflammatory potential and may be applied therapeutically in the treatment of IBD.

Budesonide-liposomes inclusion complex in thermosensitive gel alleviates DSS-induced ulcerative colitis in mice

Purpose A novel formulation for Ulcerative Colitis (UC) treatment by rectal administration with budesonide liposomes (Bud Lip) and thermosensitive gel (Gel) was developed for future clinical use. To evaluate the anti-inflammatory activity and colon mucosal protection of this novel formulation compared with the other three in mice. Methods Bud Lip was prepared by reverse evaporation method and then dispersed in solutions with PL407 and PL188 by a cold method. Male mice were induced to UC by dextran sulfate sodium (DSS) and were treated for 14 days by rectal administration, as follows: Bud enema (a conventional suspension formulation); Bud Lip; Bud Gel; Bud Lip-Gel; saline. And a negative control without colitis was also used. Disease activity index (DAI), and macroscopic and microscopic damage scores in colon tissues were used to evaluate the effect of therapy. The levels of IL-6 and IL-10 in serum and the concentrations of TNF-α and IL-10 and myeloperoxidase (MPO) activity in colon tissue were also introduced. Results In UC mice model, Bud Lip-Gel showed inflammation was alleviated significantly, and the treatment was highly associated with lower DAI, less macroscopic and microscopic colonic damage and downregulation of pro-inflammatory cytokines TNF-α, IL-6 and MPO. Bud Lip-Gel had advantages over Bud, Bud Lip, Bud Gel in the treatment of active UC. Conclusion Novel Bud liposomes complex in thermosensitive Gel effectively mitigated symptoms, alleviated macroscopic and microscopic colon damage, and reduced inflammatory reaction in UC mice, which might be a potential strategy for UC treatment.

Cytokine transcriptome profiling in acute experimental canine atopic dermatitis skin lesions after IL-31 inhibition with lokivetmab.

The caninised monoclonal antibody lokivetmab (LKV), directed at interleukin (IL)-31, is very effective at controlling pruritus in most dogs with atopic dermatitis (AD). However, evidence exists that IL-31 is not required for the induction of acute allergic skin inflammation, which might explain why this treatment is less efficacious in some dogs with AD. To compare the comprehensive transcriptome analysis of house dust mite (HDM)-sensitised dogs with and without treatment with LKV to attest our hypothesis that LKV does not majorly affect acute cytokine/chemokine production. Six HDM-sensitised atopic Maltese-beagle dogs. In this cross-over study, the cytokine profiling of acute AD skin lesions was compared by RNA sequencing (RNA-Seq), with or without LKV-induced inhibition of IL-31. Skin biopsies were obtained from each dog at 0, 6, 12, 24, 48, and 96 h after epicutaneous HDM allergen provocation. Macroscopic and microscopic skin lesion scores were not significantly different between the LKV- and nontreatment groups at any time points. Likewise, the results of RNA-Seq analysis revealed no significant difference in the messenger (m)RNA expression of the major cytokines between these two groups. In LKV-treated dogs, IL6, IL9, IL13, IL33, CCL17, and CCL22 were significantly upregulated compared to their baseline expression levels, suggesting that these cytokines are unaffected by IL-31 inhibition. IL-31 inhibition is insufficient to prevent the expression of other proinflammatory mediators in acute AD and these could be considered as other potential therapeutic targets.

Evaluation of analgesic and prophylactic activity of curcumin against chikungunya-infected acute/chronic arthralgic mice.

Chikungunya virus (CHIKV) infection, a global public health problem, might lead to acute/chronic polyarthritis causing long-term morbidity among infected patients. But, except nonsteroidal anti-inflammatory drugs(NSAIDs) with gastrointestinal, cardiovascular, and immune-related side-effects, no Food and Drug Administration(FDA)-approved analgesic drug is available till date for the treatment of CHIKV-induced arthritis. Curcumin, a plant product with minimal toxicity has been FDA-approved as a Generally Recognized As Safe drug. This study aimed to determine the analgesic and prophylactic effect of curcumin, if any, among CHIKV-induced arthralgic mice. Arthritic pain was evaluated by von Frey assay, locomotory behavior by open-field test, and feet swelling by calipers. Cartilage integrity and proteoglycan loss were evaluated by Safranin O staining followed by Osteoarthritis Research Society International (OARSI), Standardized Microscopic Arthritis Scoring of Histological sections (SMASH) score, and type II collagen loss by immunohistochemistry. Mice were administered high (HD), mid (MD), and low (LD) curcumin doses, before (PT: pretreatment), during (CT: cotreatment) and after (Post-T: posttreatment) CHIKV-infection. Curcumin treatment using PTHD (2000 mg/kg), CTHD , and Post-TMD (1000 mg/kg) significantly alleviated CHIKV-induced arthritic pain by improving pain-threshold, locomotory behavior and reducing feet swelling of infected mice. Also, decreased proteoglycan loss and cartilage erosion with lower OARSI, SMASH scores were observed among these three subgroups compared to infected ones. Compared to infected ones, one- to twofold increased intensity of type II collagen in knee medial femoral condyle and medial tibial plateau regions of these subgroups was observed by immunohistochemical staining. Thus, this study highlighted both the analgesic (CT, Post-T), and prophylactic (PT) activity of curcumin in alleviating CHIKV-induced acute/chronic arthritis within mouse model.

AN ALTERNATIVE ANTIVIRAL THERAPY OF NEWCASTLE DISEASE IN BROILER CHICKENS: A CLINICAL STUDY OF METHANOLIC NEEM LEAVES EXTRACT

Newcastle disease (ND) is an important viral disease that threatens the global poultry industry. The urgent need for a safe and effective antiviral alternative prompted us to evaluate neem methanolic leaf extract against Newcastle disease virus (NDv) in broilers. A total of Sixty Cobb chicks (day old) were allocated randomly into 4 equal groups; group A was a control negative, and group B was a control positive. Groups C and D received a methanolic neem leaf extract (MNLE) in drinking water for five days at 500 and 1000 µg/kg BW, respectively. At 25th days old, chicks in groups B, C and D were challenged via the oculonasal route with 0.2 ml of virulent NDv. The use of MNLE in groups C and D significantly reduced morbidity and mortality as well as the macroscopic and microscopic scoring lesions of all examined organs compared to the infected untreated group B. The high dose of MNLE (1000 µg/ kg BW; group D) was more efficient and significant in relieving the clinical and pathological abnormalities caused by ND challenge compared with the low dose (500 µg/ kg BW; group C). Moreover, positive effects of the herbal treatment on the experimentally ND-infected chickens were evidenced by reducing viral RNA concentrations in the oropharyngeal swabs at 3, 5, and 7 days post challenge and the infectivity titer of the virus isolated from the trachea, spleen, and cecal tonsils at 7 days post challenge. In conclusion, MNLE possesses potential antioxidant to have a power to control NDv shedding and infection. So, MNLE could be a source of inspiration for new alternative antivirals.

Icosapent ethyl alleviates acetic acid-induced ulcerative colitis via modulation of SIRT1 signaling pathway in rats.

Ulcerative colitis (UC) is a global inflammatory bowel disease. This study aimed to assess the effects of icosapent ethyl on acetic acid-induced colitis in rats as well as the underlying mechanisms involved. 36 male Wister rats were equally divided into six groups: control, UC, mesalamine 100mg/kg, icosapent 150mg/kg, icosapent 300 mg/kg, and EX527-icosapent 300mg/kg groups. Except for control group, UC was induced by acetic acid instillation into colon. Drugs were administered once daily for one week then under thiopental anaesthesia, colons were excised. Colitis macroscopic and microscopic scores were assessed. A part of colon was homogenized for detection of malondialdehyde (MDA), inerleukin1 (IL-1β), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), phosphorylated Akt (pAkt) and caspase 3 levels. Silent information regulator 1 (SIRT1), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2 (Nrf2) mRNA expressions were detected. Mallory-stained colonic sections were examined for collagen fibres detection. Immunohistochemistry of NF-κB and p53 expressionsin colonic sections were assessed. Acetic acid induced colitis with increments in MDA, IL-1β, TNF-α, and caspase 3 levels while decreased SOD, pAkt, SIRT1, HO-1, and Nrf2 with increased collagen fibres as well as NF-κB and p53. Icosapent decreased macro& microscopic colitis scores, MDA, IL-1β, TNF-α, and caspase 3 levels while increased SOD, pAkt, SIRT1, HO-1, and Nrf2 with decreased collagen fibres as well as NF-κB and p53. The effects of icosapent 300mg/kg were similar to mesalamine. Icosapent effects were antagonized by EX527. Icosapent alleviated acetic acid-induced colitis via its anti-inflammatory, antioxidant, and anti-apoptotic effects mediated in part by SIRT1 pathway activation.

Ferulic Acid Treats Gastric Ulcer via Suppressing Oxidative Stress and Inflammation

(1) Background: The aim of the present study was to evaluate the gastroprotective potential of ferulic acid (FA) on indomethacin-induced gastric ulcers in rats with macroscopic and microscopic examinations along with biochemical assays. (2) Methods: After 24 h starvation, the ulcer was induced in male Sprague-Dawley rats by subcutaneous indomethacin (25 mg/kg) injection. Fifteen minutes after ulcer induction, rats were treated with either tween 80 or FA. FA was given by oral gavage at 100 mg/kg, 250 mg/kg, and 500 mg/kg. In the fourth hour, rats were euthanized and collected gastric samples were evaluated macroscopically and microscopically. Antioxidant parameters including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and inflammatory parameters comprising of myeloperoxidase (MPO), Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1β, IL-6 and Nuclear Factor Kappa-B (NF-κB) p65 levels were also determined. (3) Results: Indomethacin injection significantly increased the macroscopic and microscopic scores. In addition, it increased the gastric MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 levels but reduced SOD and GSH content. Treatment with FA significantly improved the gastric injury macroscopically and microscopically. Moreover, FA displayed a marked decrease in the gastric levels of MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 and a significant increase in SOD and GSH compared to the INDO group. Ultimately, 250 mg/kg FA was determined as the most effective dose. (4) Conclusion: Our results revealed that FA has a gastroprotective effect against indomethacin-induced gastric ulcers in rats due to its antioxidant and anti-inflammatory properties. As a result, FA may be a potential treatment choice for gastric ulcers.

Neuropeptide W Exhibits Preventive and Therapeutic Effects on Acetic Acid-Induced Colitis via Modulation of the Cyclooxygenase Enzyme System.

The novel peptide neuropeptide W (NPW) was originally shown to function in the control of feeding behavior and energy homeostasis. The aim of this study was to elucidate the putative preventive and therapeutic effects of NPW on colitis-associated oxidative injury and the underlying mechanisms for its action. Sprague-Dawley rats in the acute colitis groups received NPW (0.5, 1 or 5µg/kg/day) injections prior to induction of colitis with acetic acid, while the chronic colitis groups were treated after the induction of colitis. In both acute and chronic colitis (CC) groups, treatments were continued for 5days and the rats were decapitated at the 24th hour of the last injections and colon tissues were collected for assessments. NPW pretreatment given for 5days before colitis induction, as well as treating rats with NPW during the 5-day course of CC, abolished colonic lipid peroxidation. NPW treatment prevented colitis-induced reduction in blood flow, diminished neutrophil infiltration, and pro-inflammatory cytokine responses. NPW pretreatment only at the higher dose reduced colonic edema and microscopic score and preserved colonic glutathione stores. Elevations in cyclooxygenase (COX) enzyme activity and COX-1 protein level during the acute phase of colitis as well as reduction in COX-2 were all reversed with NPW pretreatment. In contrast, NPW treatment was effective in reducing the elevated COX-2 concentration during the chronic phase. NPW alleviates acetic acid-induced oxidative colonic injury in rats through the upregulation of colonic blood flow as well as the inhibition of COX-2 protein expression and pro-inflammatory cytokine production.

Do YouTube videos on microscopic varicocelectomy provide reliable information?

This study aimed to assess the quality of YouTube videos about microscopic varicocelectomy. On November 20, 2022, a YouTube search for "Microscopic Varicocelectomy" was conducted. Non-English videos uploaded by producers for commercial purposes that lacked audio and subtitles were excluded from the study. A total of 50 videos were evaluated using the Journal of the American Medical Association Benchmark Score and the Global Quality Score, both of which are recognized internationally. Additionally, the researcher developed the Microscopic Varicocelectomy Score to evaluate the videos' technical content. The upload source, video length, number of views, likes, dislikes, and video power indexes were evaluated. The Global Quality Score, Journal of the American Medical Association Benchmark Score, and Microscopic Varicocelectomy Score of the academically prepared videos were significantly higher than those of the physician-prepared videos (p<0.05). The Global Quality Score, Journal of the American Medical Association Benchmark Score, and Microscopic Varicocelectomy Score of uploaded videos with audio, audio, and subtitles were significantly higher than those with only subtitles (p<0.05). The video duration was positively correlated with Journal of the American Medical Association Benchmark Score, Global Quality Score, and Microscopic Varicocelectomy Score. The video power index had a strong positive correlation with the number of likes. Moreover, a strong positive correlation was observed, indicating that the Global Quality Score and Journal of the American Medical Association Benchmark Score increased as the Microscopic Varicocelectomy Score increased. YouTube videos regarding microscopic varicocelectomy were of notably low quality. If the video content created by specialist physicians and academic centers is more meticulously organized, more accurate data can be transmitted. Consequently, viewing video content may not be advised based on the available data.

Articular Cartilage Repair After Implantation of Hyaline Cartilage Beads Engineered From Adult Dedifferentiated Chondrocytes: Cartibeads Preclinical Efficacy Study in a Large Animal Model

Background: Chondrocyte-based cell therapy to repair cartilage has been used for >25 years despite current limitations. This work presents a new treatment option for cartilage lesions. Hypothesis: High-quality hyaline cartilage microtissues called Cartibeads are capable of treating focal chondral lesions once implanted in the defect, by complete fusion of Cartibeads among themselves and their integration with the surrounding native cartilage and subchondral bone. Study Design: Controlled laboratory study. Methods: Cartibeads were first produced from human donors and characterized using histology (safranin O staining of glycosaminoglycan [GAG] and immunohistochemistry of collagen I and II) and GAG dosage. Cartibeads from 6 Göttingen minipigs were engineered and implanted in an autologous condition in the knee (4 or 5 lesions per knee). One group was followed up for 3 months and the other for 6 months. Feasibility and efficacy were measured using histological analysis and macroscopic and microscopic scores. Results: Cartibeads revealed hyaline features with strong staining of GAG and collagen II. High GAG content was obtained: 24.6-µg/mg tissue (wet weight), 15.52-µg/mg tissue (dry weight), and 35 ± 3-µg GAG/bead (mean ± SD). Histological analysis of Göttingen minipigs showed good integration of Cartibeads grafts at 3 and 6 months after implantation. The Bern Score of the histological assay comparing grafted versus empty lesions was significant at 3 months (grafted, n = 10; nongrafted, n = 4; score, 3.3 and 5.3, respectively) and 6 months (grafted, n = 11; nongrafted, n = 3; score, 1.6 and 5.1). Conclusion: We developed an innovative 3-step method allowing, for the first time, the use of fully dedifferentiated adult chondrocytes with a high number of cell passage (owing to the extensive amplification in culture). Cartibeads engineered from chondrocytes hold potential as an advanced therapy medicinal product for treating cartilage lesions with established efficacy. Clinical Relevance: This successful preclinical study, combined with standardized manufacturing of Cartibeads according to good manufacturing practice guidelines, led to the approval of first-in-human clinical trial by the ethics committee and local medical authority. The generated data highlighted a promising therapy to treat cartilage lesions from a small amount of starting biopsy specimen. With our innovative cell amplification technology, very large lesions can be treated, and older active patients can benefit from it.