{"title":"Ifosfamide, Carboplatin, and Etoposide as Neoadjuvant Chemotherapy in Patients With Neurofibromatosis Type I-related Malignant Peripheral Nerve Sheath Tumors.","authors":"Junji Wasa, Hirohisa Katagiri, Hideki Murata, Shunichi Toki, Kan Ito, Mitsuru Takahashi","doi":"10.21873/invivo.14022","DOIUrl":"10.21873/invivo.14022","url":null,"abstract":"<p><strong>Background/aim: </strong>The role of chemotherapy for malignant peripheral nerve sheath tumors (MPNSTs) remains controversial, particularly in neurofibromatosis type 1 (NF1)-related MPNST (NF1-MPNST). This study aimed to assess the clinical outcomes of patients with NF1-MPNST who underwent curative treatment comprising neoadjuvant chemotherapy followed by wide resection.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed data from patients with NF1-MPNST who received preoperative chemotherapy. The regimen was ifosfamide 1.5 g/m<sup>2</sup> on days 1-3, carboplatin 400 mg/m<sup>2</sup> on day 3, and etoposide 100 mg/m<sup>2</sup> on days 1-3 (ICE). Radiographic response, overall survival, and toxicity were evaluated.</p><p><strong>Results: </strong>We analyzed data from 12 patients treated between 2005 and 2023. All patients received two to four courses of ICE without concomitant radiation therapy, with a median 20.4% (range=-14-63%) reduction in tumor size. According to the RECIST criteria, four patients had partial responses and eight had stable disease. The 5-year overall survival rate was 81.8%. The survival rate of patients with a partial response was 100%. Toxicities included myelosuppression, nausea, and general fatigue. Three patients received platelet transfusions. Three patients discontinued neoadjuvant chemotherapy because of patient preference.</p><p><strong>Conclusion: </strong>In this study, we achieved more favorable outcomes than those in previous studies. Neoadjuvant chemotherapy, which included the ICE regimen, not only resulted in tumor shrinkage in eight of 12 cases but also demonstrated a good prognosis when tumor shrinkage was achieved. These findings suggest that neoadjuvant chemotherapy with the ICE regimen may be a promising approach for managing NF1-MPNST.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"2267-2276"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of Adjuvant Chemotherapy Following Neoadjuvant Concurrent Chemoradiotherapy and Total Mesorectal Excision in Rectal Cancer.","authors":"Yu-Shih Liu, Jen-Kou Lin, Tzu-Chen Lin, Wei-Shone Chen, Shung-Haur Yang, Huann-Shenn Wang, Shih-Ching Chang, Yuan-Tzu Lan, Chun-Chi Lin, Hung-Hsin Lin, Jeng-Kai Jiang","doi":"10.21873/invivo.14027","DOIUrl":"10.21873/invivo.14027","url":null,"abstract":"<p><strong>Background/aim: </strong>This study investigated the efficacy of adjuvant chemotherapy (ACT) after total mesorectal excision (TME) for rectal cancer in patients who responded well to neoadjuvant concurrent chemoradiotherapy (nCCRT).</p><p><strong>Patients and methods: </strong>This retrospective study included patients with rectal cancer treated at Taipei Veterans General Hospital (2009-2017). Among 302 patients who underwent nCCRT and TME, 178 good responders [pathologic complete response (pCR), pT1, or pT2] were analyzed. Patients were grouped based on ACT administration. Primary outcomes included disease-free survival (DFS) and recurrence. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess ACT efficacy.</p><p><strong>Results: </strong>The ACT group (n=96) had poorer baseline disease characteristics, including higher initial clinical T and N stages. However, recurrence rates did not differ significantly between ACT and non-ACT groups (23.2% <i>vs</i>. 17.7%, <i>p</i>=0.271). DFS curves showed no significant difference between ACT and non-ACT groups (<i>p</i>=0.360). Multivariable analysis confirmed that ACT was not significantly associated with DFS [adjusted hazard ratio (aHR)=0.76, 95% confidence interval (CI)=0.37-1.59]. However, the advanced surgical pT stage (pT3-pT4) was an independent predictor of recurrence (aHR=3.24, 95%CI=1.01-10.38, <i>p</i>=0.047).</p><p><strong>Conclusion: </strong>The role of ACT remains inconclusive after TME for rectal cancer in patients who respond well to nCCRT. Surgical pT stage, particularly pT3 and pT4, remain a significant predictor of recurrence, emphasizing its importance in risk stratification.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"2311-2319"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vivoPub Date : 2025-07-01DOI: 10.21873/invivo.14000
Merve Beker, Busenur Bolat, Bahar Sarikamis Johnson, Nilufer Ercin, Rabia Kalkan Cakmak, Sare B Kaya, Nail Besli, Ulkan Celik, Mustafa C Beker
{"title":"NeuroD2 Modulates Hippocampal Neuronal Organization and Axon Guidance During Aging.","authors":"Merve Beker, Busenur Bolat, Bahar Sarikamis Johnson, Nilufer Ercin, Rabia Kalkan Cakmak, Sare B Kaya, Nail Besli, Ulkan Celik, Mustafa C Beker","doi":"10.21873/invivo.14000","DOIUrl":"10.21873/invivo.14000","url":null,"abstract":"<p><strong>Background/aim: </strong>Biological aging refers to the progressive deterioration of an organism's functions due to accumulated cellular and molecular damage. NeuroD2, a critical transcription factor, plays a crucial role in neuronal development and synaptic maturation. This study investigates the role of NeuroD2 in hippocampal neuron organization, focusing on hilar mossy cells during aging, and employs bioinformatics to identify NeuroD2 targets linked to cellular aging.</p><p><strong>Materials and methods: </strong>We used 21 adult C57Bl/6 mice, categorized into three age groups: young (2 months), old (12 months), and very old (24 months). Mice were administered BrdU intraperitoneally for three consecutive days, 10 days before euthanasia. The brains were harvested and analyzed using immunofluorescence, Western blotting, and quantitative real-time PCR to evaluate NeuroD2 expression and associated signaling pathways in hippocampal tissue. Additionally, bioinformatics analysis was performed using two open-access datasets (ProteomeXchange Consortium, Dataset identifier: PXD043352; Gene Expression Omnibus, GEO: GSE67539) and to explore potential interactions between NeuroD2 targets and biological aging components.</p><p><strong>Results: </strong>Our results revealed that NeuroD2 expression changed significantly with age and correlated with AKT signaling. Moreover, we identified a potential link between NeuroD2 activity and the AKT pathway, indicating NeuroD2's role in mitigating aging-related stress. Bioinformatics analysis identified 513 down-regulated and 638 up-regulated proteins, with NeuroD2 targets involved in axonal projection showing increased expression in older mice. Contrary to expectations, pathway enrichment analysis highlighted axon guidance molecules rather than oxidative stress markers.</p><p><strong>Conclusion: </strong>This study underscores NeuroD2's critical role in preserving hippocampal integrity and reveals molecular mechanisms underlying age-related neuronal changes. Our findings provide insights into the role of NeuroD2 in regulating key pathways during healthy aging, potentially mitigating the impacts of aging.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"2050-2065"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vivoPub Date : 2025-07-01DOI: 10.21873/invivo.14049
Yi-Yen Tsai, Jeng-Wei Lu, Hao Yen, Chih-Chien Wang
{"title":"Painful Angiomyoma of the Heel Region: A Rare Case Report.","authors":"Yi-Yen Tsai, Jeng-Wei Lu, Hao Yen, Chih-Chien Wang","doi":"10.21873/invivo.14049","DOIUrl":"10.21873/invivo.14049","url":null,"abstract":"<p><strong>Background/aim: </strong>Angiomyomas are rare benign smooth muscle tumors originating from the tunica media of blood vessel walls, most frequently affecting the lower extremities in middle-aged women.</p><p><strong>Case report: </strong>We report the case of a 51-year-old female with a six-month history of a painful, palpable mass in the right heel. Physical examination revealed a soft, mobile, and tender subcutaneous nodule. Ultrasound imaging identified a 0.5 cm well-defined hypoechoic lesion in the subcutaneous layer, without internal blood flow, initially suspected to be an epidermoid cyst or fibrous tumor. Surgical excision of the lesion was performed, and histopathological analysis revealed a well-encapsulated tumor consisting of spindle-shaped cells with eosinophilic cytoplasm and bland nuclei, accompanied by vascular components. Immunohistochemical staining confirmed positive expression of SMA, establishing the diagnosis of angiomyoma. The patient experienced an uneventful postoperative recovery.</p><p><strong>Conclusion: </strong>This case highlights the diagnostic challenges of angiomyomas, given their nonspecific clinical presentation and imaging findings. While magnetic resonance imaging may reveal characteristic features such as strong gadolinium enhancement, definitive diagnosis relies on histopathological evaluation. Clinicians should include angiomyoma in the differential diagnosis of painful subcutaneous masses in the foot and ankle, particularly in middle-aged women. Surgical excision remains the definitive diagnostic and therapeutic approach, with low recurrence rates reported.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"2485-2488"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relationship Between Anthracycline-cyclophosphamide Regimens and Docetaxel Monotherapy in Oral Mucositis Development.","authors":"Yoshitaka Saito, Tatsuhiko Sakamoto, Yoh Takekuma, Masato Takahashi, Tomohiro Oshino, Mitsuru Sugawara","doi":"10.21873/invivo.14021","DOIUrl":"10.21873/invivo.14021","url":null,"abstract":"<p><strong>Background/aim: </strong>We have previously reported that patients experiencing oral mucositis (OM) during anthracycline-cyclophosphamide treatment develop symptoms following subsequent docetaxel-containing chemotherapy for perioperative breast cancer therapy. However, the concomitant use of pertuzumab and trastuzumab with docetaxel has also been suggested as a significant risk factor for OM. This study aimed to further evaluate the direct relationship of OM with anthracycline-cyclophosphamide treatment and docetaxel monotherapy.</p><p><strong>Patients and methods: </strong>Patients with breast cancer who underwent anthracycline-cyclophosphamide treatment followed by docetaxel monotherapy as perioperative therapy (n=63) were divided into control and OM-experience groups based on the absence or presence of OM development during prior anthracycline-cyclophosphamide treatment, and retrospectively evaluated. The primary endpoint was the comparison of all-grade OM incidence in the first docetaxel cycle between the two groups. The incidence of OM and dysgeusia was also assessed across all treatment cycles.</p><p><strong>Results: </strong>The incidence of all-grade OM was 42.9% in the OM-experience group and 9.5% in the control group during the first cycle (<i>p</i>=0.006) and 47.6% and 11.9% across all treatment cycles (<i>p</i>=0.004), thereby achieving the primary endpoint. In contrast, the incidence of grade ≥2 OM in both settings was higher in the OM-experience group than in the control group, although the difference was not statistically significant (14.3% <i>vs</i>. 2.4%, <i>p</i>=0.10 for both settings). Moreover, the incidence of dysgeusia did not differ between the two groups.</p><p><strong>Conclusion: </strong>Patients exhibiting OM during prior anthracycline-cyclophosphamide treatment were significantly more likely to develop symptoms during subsequent docetaxel monotherapy for perioperative breast cancer therapy.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"2259-2266"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk Factors Associated With Thrombocytopenia Induced by Intravenous Immunoglobulin Formulations: An Analysis Using the JADER database.","authors":"Yoshihiro Nishita, Natsuko Ishida, Hirofumi Nagai, Togen Masauji, Junko Ishizaki","doi":"10.21873/invivo.14028","DOIUrl":"10.21873/invivo.14028","url":null,"abstract":"<p><strong>Background/aim: </strong>Thrombocytopenia is a serious adverse event observed with intravenous immunoglobulin formulations (IVIg). There have been some individual case reports of such events, but to our knowledge, no epidemiological studies have been reported. In this study, the risk of IVIg-induced thrombocytopenia and factors associated with IVIg-induced thrombocytopenia were examined using the Japanese Adverse Drug Event Report database.</p><p><strong>Patients and methods: </strong>Data spanning from April 2004 to August 2024 were used. The association between IVIg and thrombocytopenia was evaluated using the reporting odds ratio (ROR). The reports of IVIg-induced thrombocytopenia events were evaluated by disease and aggregated by disease group. Factors associated with IVIg-induced thrombocytopenia were detected using multiple logistic regression with age, sex, formulation method, and disease group as explanatory variables and adjusted RORs were calculated.</p><p><strong>Results: </strong>The IVIgs examined were significantly associated with thrombocytopenia. Pemphigoid was the most frequently reported disease, followed by Kawasaki disease and polymyositis/dermatomyositis. Immune-mediated skin diseases were the most frequently reported disease group, followed by Kawasaki disease, immune-mediated neurological diseases, and immune-mediated muscular diseases. Multiple logistic regression analysis showed that at age 60 years or older, immune-mediated skin diseases and immune-mediated muscular diseases were independently associated with significantly increased RORs.</p><p><strong>Conclusion: </strong>This study suggests that IVIg can induce thrombocytopenia and that thrombocytopenia should be assessed in patients with immune-mediated skin diseases, immune-mediated muscular diseases and in the elderly.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"2320-2327"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Usefulness of the Modified Advanced Lung Cancer Inflammation Index (mALI) as a Prognostic Factor in Patients With Esophageal Cancer who Have Undergone Curative Resection.","authors":"Sosuke Yamamoto, Toru Aoyama, Yukio Maezawa, Itaru Hashimoto, Ryuki Esashi, Kazuki Otani, Suguru Nukada, Tetsushi Ishiguro, Kiyoko Shimada, Keisuke Kazama, Koji Numata, Mamoru Uchiyama, Rei Hatayama, Ayako Tamagawa, Aya Saito, Norio Yukawa","doi":"10.21873/invivo.14013","DOIUrl":"10.21873/invivo.14013","url":null,"abstract":"<p><strong>Background/aim: </strong>In several previous studies, the modified advanced lung cancer inflammation index (mALI) has been reported to be a useful prognostic factor in non-small cell lung cancer. This study aimed to demonstrate the relationship between mALI and the oncological prognosis of patients with esophageal cancer (EC) who underwent curative treatment and to clarify the underlying mechanism.</p><p><strong>Patients and methods: </strong>We retrospectively followed up patients who underwent curative resection of esophageal cancer at Yokohama City University between 2000 and 2020 and extracted clinical data from their medical records. mALI was defined as follows: mALI=[L3 muscle index (L3MI) (cm<sup>2</sup>/m<sup>2</sup>)×albumin (g/l)]/neutrophil-to-lymphocyte ratio (NLR) [neutrophil count÷lymphocyte count].</p><p><strong>Results: </strong>A total of 196 patients were selected for this study, and the cutoff value for mALI was set separately for male and females. When the cutoff value was set at 10 for males and 12 for females, 84 patients were assigned to the mALI-low group and 112 patients were assigned to the mALI-high group. A survival analysis revealed that the 5-year overall survival (OS) rate was 50.3% in the mALI-low group and 62.5% in the mALI-high group (<i>p</i>=0.014). A multivariate analysis of OS revealed that mALI was an independent prognostic factor. The 5-year recurrence-free survival (RFS) rates were 33.0% in the mALI-low group and 44.9% in the mALI-high group (<i>p</i>=0.044). The multivariate analysis of RFS revealed that mALI was an independent prognostic factor. In addition, the mALI-low group had a higher rate of hematogenous metastasis than the mALI-high group.</p><p><strong>Conclusion: </strong>mALI is associated with the oncological prognosis of patients with EC who have undergone radical resection <i>via</i> several mechanisms and is a useful prognostic factor.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"2176-2185"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Association of Glucose Metabolism Disorders and Acne in Women With Polycystic Ovary Syndrome (PCOS).","authors":"Eftichia Damoulaki, Dimos Sioutis, Eleni P Georgiadi, Eftichios Trakakis, Georgios Mastorakos, Alexander Katoulis, Konstantinos Louis, Dimitrios Panagiotopoulos, Nikolaos Machairiotis, Vasilios Pergaliotis, Periklis Panagopoulos, Chrysi Christodoulaki","doi":"10.21873/invivo.14017","DOIUrl":"10.21873/invivo.14017","url":null,"abstract":"<p><strong>Background/aim: </strong>Acne is a common dermatological manifestation of polycystic ovary syndrome (PCOS), a prevalent endocrinological disorder among women of reproductive age. A growing body of evidence highlights glucose metabolism disorders, including insulin resistance, in the context of PCOS. This study aimed to investigate the association of acne and its severity with insulin resistance in a population of women with PCOS.</p><p><strong>Patients and methods: </strong>A total of 305 women with PCOS aged between 17-35 years were included in this retrospective observational study. Anthropometric, hormonal, biochemical, and ultrasonographic markers of PCOS were analyzed in relation to insulin resistance indices, including HOMA-IR and QUICKI.</p><p><strong>Results: </strong>Acne was present in 56.4% of participants, with 52.1% exhibiting mild and 4.3% severe cases. Younger age (<i>p</i>=0.006), higher DHEAS levels (<i>p</i>=0.001), and glucose metabolism disorders, including fasting glucose >100 mg/dl, <i>p</i>=0.026 and 2-h glucose higher than 140 mg/dl (<i>p</i>=0.019), were significantly associated with acne. Multivariate analysis indicated younger age (OR=0.94, <i>p</i>=0.012), elevated DHEAS levels (OR=1.03; <i>p</i>=0.006), and 2-h glucose levels >140 mg/dl (OR=3.25, <i>p</i>=0.029) as independent predictors of acne severity.</p><p><strong>Conclusion: </strong>This study indicates the association between insulin resistance and hyperandrogonemia with both the presence and severity of acne in PCOS. These findings align with contemporary literature and underscore the importance of addressing the hormonal and metabolic factors in the etiological management of acne in PCOS.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"2219-2227"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term Safety Pharmacology and Musculoskeletal Changes of HMGB1 Box A Gene Therapy in Middle-aged Monkeys.","authors":"Sukanya Jaroenporn, Tayanee Chundee, Sakawdaurn Yasom, Lalitta Suriya-Arunroj, Motee Chimngam, Nutchanat Suttisan, Suchinda Malaivijitnond, Apiwat Mutirangura","doi":"10.21873/invivo.13994","DOIUrl":"10.21873/invivo.13994","url":null,"abstract":"<p><strong>Background/aim: </strong>HMGB1 Box A gene therapy is a promising therapeutic approach for age-associated diseases, based on evidence from <i>in vitro</i> and <i>in vivo</i> studies in rodents. This study aimed to evaluate long-term safety and musculoskeletal change of the Box A gene in non-human primates.</p><p><strong>Materials and methods: </strong>Perimenopausal monkeys were intravenously injected with a control plasmid (PC group) or Box A plasmid (Box A group) once a week for eight weeks, and were observed for one year. The safety pharmacology, blood biochemistry and hematology, bone mineral density, bone geometry, and muscle density were assessed and compared between the groups.</p><p><strong>Results: </strong>The safety pharmacological tests, general clinical observations, and evaluation of the central nervous, cardiovascular, and respiratory systems revealed no safety concerns. The response of the musculoskeletal system to Box A showed that the radius and tibia exhibited opposing bone density and size changes between the PC and Box A groups. Box A attenuated the age-related increase in bone mass and decrease in bone size at the radial metaphysis. Box A promoted cortical bone accumulation in the tibial diaphysis. The PC group, but not the Box A group, showed elevated blood glucose levels starting from the 48<sup>th</sup> week of the experiment. Box A group trended to gain less weight than the PC group, without experiencing muscle loss.</p><p><strong>Conclusion: </strong>This study indicated that Box A was safe over a 56-week observation period, causing no adverse clinical symptoms. Notably, it mitigated age-associated phenotypes, including improved bone health, lowered blood glucose, and reduced weight gain in perimenopausal monkeys. These results suggest Box A as a safe rejuvenation medicine.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"1965-1983"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microvascular Damage in the Deep Mucosal <i>Lamina Propria</i> Triggers the Onset of Colitis in Dextran Sulfate Sodium-induced Colitis in Mice.","authors":"Hiroki Saijo, Hisashi Hashimoto, Seiji Arihiro, Moriaki Kusakabe, Masataka Okabe","doi":"10.21873/invivo.13986","DOIUrl":"10.21873/invivo.13986","url":null,"abstract":"<p><strong>Background/aim: </strong>Dextran sulfate sodium (DSS) is employed to induce colitis in mice for studying ulcerative colitis (UC), an inflammatory bowel disease. However, the precise mechanism underlying its action remains unclear. Microcirculatory issues in the colonic mucosa contribute to DSS-induced colitis; however, early structural changes in the local vascular system have not been thoroughly investigated. Therefore, we aimed to explore the circulatory system and mucosal circulation in the mouse colon and identify the early causes of bleeding in DSS-induced colitis.</p><p><strong>Materials and methods: </strong>A 2% DSS solution was administered to C57BL/6J mice, and on days 3, 4, and 5 of administration, colonic circulation was examined through histological analysis of the mucosa, vascular casting, and differential staining of arteries and veins by sequential infusion of a fluorescent isothiocyanate-labeled gelatin solution and a small amount of a rhodamine isothiocyanate-labeled gelatin solution.</p><p><strong>Results: </strong>By day 4, we observed increased vascular leakage, with significant changes in the mucosal vascular networks evident on day 5. Differential staining of the superior mesenteric artery and inferior mesenteric artery elucidated the boundary regions of their perfusion areas in the middle colon. DSS primarily caused vascular injury in this border zone, extending to the mid- and distal colon. Further exploration of the mucosal circulation revealed bleeding originating from the deep mucosal arteriolar plexus.</p><p><strong>Conclusion: </strong>Early vascular impairment, particularly in the deep mucosal arteriolar plexus, precedes DSS-induced colitis in mice. Understanding these vascular disturbances may provide insights into pathogenesis of inflammatory bowel disease and aid in developing early detection and intervention strategies for UC in humans.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 4","pages":"1864-1878"},"PeriodicalIF":1.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}