Histology of Bronchiolar Tumor Spread Through Air Spaces.

The clinical significance of lung tumor spread through air spaces (STAS) has been extensively studied, and is recognized as a unique pattern of invasion. Previous studies of STAS have focused primarily on STAS in alveolar spaces, whereas STAS in the bronchiolar spaces (bronchiolar STAS) has been described in only a few case reports only. Here, we examined 306 cases of primary lung adenocarcinoma and found that bronchiolar STAS was present in 18%. Bronchiolar STAS was associated with an inferior prognosis, more advanced stage, and higher histologic grade. No significant difference in clinicopathological factors or prognosis was observed between cases with bronchiolar STAS and those with alveolar STAS alone. Notably, bronchiolar STAS often occurred simultaneously with alveolar STAS and endobronchial spread of adenocarcinoma, particularly when bronchiolar STAS was present outside the main tumor. We also identified cases where bronchiolar STAS and endobronchial spread of adenocarcinoma occurred simultaneously in the same bronchi or bronchioles located outside the main tumor, as well as cases with bronchiolar STAS adjacent to intrapulmonary metastatic nodules. Our results highlight the significant role of bronchiolar STAS in the aerogenous spread of adenocarcinoma cells. Bronchiolar STAS can be regarded as a histologic variant of alveolar STAS. This study also supports the idea that STAS is not a tissue processing artifact, but a true biological process with clinical implications, offering histologic evidence of aerogenous spread in lung adenocarcinoma.

Single-centre observational study of the safety and efficacy of thoracoscopy under local anaesthesia for the management of thoracic infections.

OBJECTIVES: Thoracoscopy under local anaesthesia is widely performed to diagnose malignancies and infectious diseases. However, few reports have described the use of this procedure for diagnosing and treating intrathoracic infections. This study aimed to evaluate the safety and efficacy of thoracoscopy under local anaesthesia for the management of intrathoracic infections. RESULTS: Data from patients who underwent thoracoscopy procedures performed by chest physicians under local anaesthesia at our hospital between January 2018 and December 2023 were retrospectively reviewed. We analysed their demographic factors, reasons for the examinations, diseases targeted, examination lengths, anaesthetic methods used, diagnostic and treatment success rates, as well as any adverse events. Thirty patients were included. Of these, 12 (40%) had thoracoscopies to diagnose infections, and 18 (60%) had them to treat pyothorax. In terms of diagnosing pleurisy, the causative microorganism of origin was identified via thoracoscopy in only three of 12 (25.0%) patients. For diagnosing pyothorax, the causative microorganism was identified in 7 of 18 (38.9%) patients. Methicillin-resistant Staphylococcus aureus was the most common causative microorganism identified. The treatment success rates were very high, ranging between 94.4 and 100%, whereas the identification rate of the causative microorganisms behind infections was low, ranging between 25.0 and 38.9%. The most frequent adverse events included perioperative hypoxaemia and pain. There were two (6.7%) serious adverse events of grade ≥ 3, but none resulted in death. CONCLUSIONS: The efficacy of managing intrathoracic infections through thoracoscopy under local anaesthesia is commendable. Nonetheless, the diagnostic accuracy of the procedure, regarding the precise identification of the causative microorganisms responsible for intrathoracic infections, persists at a notably low level, presenting a substantial clinical hurdle.

Comparison of Cervical Pedicle Screw Placement Accuracy With Robotic Guidance System Versus Image Guidance System Using Propensity Score Matching.

STUDY DESIGN: A retrospective study. OBJECTIVE: To compare the accuracy of cervical pedicle screw (CPS) placement using a robotic guidance system (RGS) with that of using an image guidance system (IGS; navigation system) through propensity score matching. BACKGROUND: The RGS may provide accurate CPS placement, which may outperform IGS. However, no study has directly compared the accuracy of CPS placement with the RGS to that with the IGS. PATIENTS AND METHODS: We retrospectively reviewed the data of patients who had undergone cervical fusion surgery using CPS with the RGS or IGS. To adjust for potential confounders (patient demographic characteristics, disease etiology, and registration material), propensity score matching was performed, creating robotic guidance (RG) and matched image guidance (IG) groups. The accuracy of CPS placement from C2 to C6, where the vertebral artery runs, was evaluated on postoperative computed tomography images according to the Neo classification (grade 0 to grade 3). Furthermore, the intraoperative CPS revisions and related complications were examined. RESULTS: Using propensity score matching, 22 patients were included in the RG and matched groups each, and a total of 95 and 105 CPSs, respectively, were included in the analysis. In both the axial and sagittal planes, the clinically acceptable rate (grades 0 + 1) of CPS placement did not differ between the RG and matched IG groups (97.9% vs 94.3% and 95.8% vs 96.2%, respectively). The incidence of CPS revision was similar between the groups (2.1% vs 2.9%), and no CPS-related complications were documented. Meanwhile, the incidence of lateral breach (grades 1 + 2 + 3) was significantly lower in the RG group than in the matched IG group (1.1% vs 7.7%, P= 0.037). CONCLUSION: The RGS and IGS can equally aid in accurate and safe CPS placement in clinical settings. Nonetheless, RGS can further reduce the lateral breach, compared with IGS.

A Case of Adult-onset Still's Disease (AOSD) with Gastrointestinal Lesions.

A 51-year-old woman with fever was admitted to our hospital. A computed tomography (CT) scan showed thickened colonic walls. Colonoscopy revealed erosion in the ileum and colon. Adult-onset Still's disease (AOSD) was diagnosed due to a subsequent sore throat and skin rash. Following AOSD treatment, methylprednisolone pulse therapy, followed by prednisolone and cyclosporine, was initiated. Despite achieving a temporary improvement, relapse occurred with fever, abdominal pain, with worsening CT and endoscopic findings. The reappearance of a skin rash confirmed an exacerbation of AOSD. Tocilizumab treatment alleviated the symptoms and improved the endoscopic findings. Considering their correlation with the symptoms and endoscopic findings, the observed gastrointestinal lesions may be linked to AOSD.

Outcomes of nonrejection in weakly fluorescent intestine detected by indocyanine green fluorescence angiography: a case series of infants.

BACKGROUND: Indocyanine green fluorescence angiography, a validated noninvasive imaging technique, is used to assess tissue vascularization. Here, we report three infant patients who underwent intraoperative indocyanine green fluorescence angiography and suffered from postoperative complications caused by the lack of weak fluorescent intestinal resection and assessed residual intestinal perfusion. CASE PRESENTATION: We observed the clinical characteristics and operative findings of patients treated from January 2022 to December 2022. Indocyanine green (0.5 mg/kg) was intravenously injected. The first patient was a 29-day-old girl with surgical necrotizing enterocolitis who underwent intraoperative indocyanine green fluorescence angiography at the first- and second-look operations. The proximal jejunum was difficult to diagnose to detect blood flow during the second-look operation. The second patient was a 32-day-old boy with surgical necrotizing enterocolitis. A part of the antimesenteric mucosa of the patient that exhibited weak fluorescence was preserved; however, it formed postoperative hematomas. The third patient was a 30-day-old boy with midgut volvulus. Weak fluorescence in the intestinal wall was observed 5 cm of the small intestine from the ileocecal valve was preserved, but it formed a stricture, and the patient underwent ileocecal resection after 30 days. CONCLUSIONS: Weak fluorescence in the intestine in infants by performing indocyanine green fluorescence angiography is associated with a high risk of non-recovering ischemic lesions and postoperative complications.

Comparing interplay effects in scanned proton therapy of lung cancer: Free breathing with various layer and volume rescanning versus respiratory gating with different gate widths.

PURPOSE: We investigated interplay effects and treatment time (TT) in scanned proton therapy for lung cancer patients. We compared free-breathing (FB) approaches with multiple rescanning strategies and respiratory-gating (RG) methods with various gating widths to identify the superior irradiation technique. METHODS: Plans were created with 4/1, 2/2, and 1/4 layered/volume rescans of FB (L4V1, L2V2, and L1V4), and 50%, 30%, and 10% gating widths of the total respiratory curves (G50, G30, and G10) of the RG plans with L4V1. We calculated 4-dimensional dynamic doses assuming a constant sinusoidal curve for six irradiation methods. The reconstructed doses per fraction were compared with planned doses in terms of dose differences in 99% clinical-target-volume (CTV) (ΔD99%), near-maximum dose differences (ΔD2%) at organs-at-risk (OARs), and TT. RESULTS: The mean/minimum CTV ΔD99% values for FB were -1.0%/-4.9%, -0.8%/-4.3%, and -0.1%/-1.0% for L4V1, L2V2, and L1V4, respectively. Those for RG were -0.3%/-1.7%, -0.1%/-1.0%, and 0.0%/-0.5% for G50, G30, and G10, respectively. The CTV ΔD99% of the RGs with less than 50% gate width and the FBs of L1V4 were within the desired tolerance (±3.0%), and the OARs ΔD2% for RG were lower than those for FB. The mean TTs were 90, 326, 824, 158, 203, and 422 s for L4V1, L2V2, L1V4, G50, G30, and G10, respectively. CONCLUSIONS: FB (L4V1) is the most efficient treatment, but not necessarily the optimal choice due to interplay effects. To satisfy both TT extensions and interplay, RG with a gate width as large as possible within safety limits is desirable.

Changes in fecal microbiota during estrous cycle in healthy thoroughbred mares.

Gut microbiota plays a crucial role in various physiological processes, including the regulation of the reproductive system and steroid sex hormones. Throughout the normal estrous cycle of healthy mares, the levels of estradiol-17ß (E2) and progesterone (P4) in the blood exhibit periodic changes. To investigate the relationship between cyclic changes in steroid sex hormones and the gut microbiome of mares, we analyzed the fecal microbiota composition in healthy mares during the typical estrous cycle. Blood and fecal samples from five healthy mares were collected, E2 and P4 levels in serum were analyzed using radioimmunoassay (RIA), and the gut microbiome was analyzed by 16S rRNA sequencing. The overall richness and composition of the gut microbiota remained relatively stable during the normal estrous cycle in mares. The Linear Discriminant Analysis Effect Size analysis of the microbial composition during the follicular and luteal phases identified the Rhodococcus genus as differentially abundant. These findings indicate that the mare's gut microbiota's significant composition remains consistent throughout the estrous cycle. At the same time, specific low-abundance pathogenic bacteria exhibit changes that align with sexual hormonal fluctuations.

Moyamoya Syndrome: Differential Diagnosis in Patients With Central Nervous System Symptoms and Hyperthyroidism.

Moyamoya syndrome, known as secondary moyamoya disease, is associated with various primary illnesses, such as brain tumor, meningitis, autoimmune disease, and thyrotoxicosis, and their relations are not clear. We report a rare case of moyamoya syndrome in a patient with Graves' disease. An 18-year-old woman was admitted to our hospital due to convulsions. She had symptoms of palpitations and fatiguability for half a year and transient numbness in her left upper extremity and dysarthria for a month. In physical findings, tachycardia and diffuse thyroid swelling were noted. A blood test revealed thyrotoxicosis and antithyroid antibody, and a diagnosis of Graves' disease was obtained. Brain magnetic resonance imaging (MRI) showed bilateral internal carotid artery occlusion. We finally diagnosed the patient with moyamoya syndrome caused by Graves' disease. Moyamoya disease or syndrome can cause symptoms like a stroke, sometimes requiring neurosurgical treatment. In our case, the therapy for Graves' disease resolved the symptoms. When diagnosing moyamoya disease, it is necessary to confirm whether there are any background diseases, such as Graves' disease.

Comparison of Postoperative Respiratory Function Between Patients After Thoracoscopic and Open Lobectomy.

Purpose: This study aimed to compare respiratory functions of patients after thoracoscopic lobectomy (TS) with those after thoracotomy (TR). Methods: This retrospective study was conducted in two centers, one of which adapted TS as a standard procedure in 2009 and the other performs it via TR. Data on patients who underwent lobectomy for congenital lung disease between 2009 and 2021 and underwent pulmonary function test (spirometry) were collected. Results: Ten patients underwent TS and 36 underwent TR. Distribution based on sex, prenatal diagnosis, pathological diagnosis, and resected lobe were similar between the two groups. The median [interquartile range] age at procedure in the TR group was significantly smaller than that in the TS group (13 [11-18] months versus 38 [13-79] months, P = .03). The procedure duration in the TR group was significantly shorter than that in the TS group (230 [171-264] minutes versus 264 [226-420] minutes, P = .02). Pulmonary function test was conducted at the age of eight in both groups, but the interval between the procedure, and the test was significantly shorter in the TS group (TR: 7 [5-8] years versus TS: 5 [2-7] years, P = .03). The ratio of forced vital capacity compared to predicted one (TR: 86.6 [76.6-95.3] versus TS: 88.7 [86.8-89.1], P = .58) and the ratio of forced expiratory volume in 1 second against that predicted (TR: 84.0 [80.5-88.7] versus TS: 88.7 [86.8-89.1], P = .08) were not significantly different between the two groups. Conclusions: Although TR was performed earlier than TS, respiratory function was similar between the two groups.

Recent treatment and prognosis in 643 patients with extramammary Paget's disease.

Information about extramammary Paget's (EMPD) treatment is limited because of the rarity of the disease. The prognosis differs between in situ EMPD and invasive EMPD; therefore, therapy should be planned according to the disease stage. We collected data on 643 EMPD cases treated between 2015 and 2019 in Japan and assessed recent trends in EMPD treatment and prognosis based on the EMPD-oriented TNM staging. Among the 643 patients, 317 had stage 0 (49.3%), 185 had stage I (28.8%), 51 had stage II (7.9%), 18 had stage IIIA (2.8%), 48 had stage IIIB (7.5%) and 24 had stage IV (3.7%) disease. Each stage showed a distinct survival curve, with the exception of stages II and IIIA. Curative surgery was most common in patients with stage 0-III disease. Chemotherapy was the first-line therapy, mainly in patients with stage IIIB and IV disease, most commonly with docetaxel (DTX), followed by DTX + tegafur gimeracil oteracil potassium (TS-1) and TS-1. Patients with local disease exhibited a 4.4% recurrence rate. Univariate analysis revealed no prognostic differences according to age, sex or primary tumour site. SLNB was not related to disease-specific survival. In multivariate analysis, female sex significantly predicted local relapse in stage 0-I (HR 3.09; 95% CI, 1.13-8.43), and initial treatment with curative surgery was significantly protective in terms of disease-specific survival in stage II-IIIA (HR, 0.17; 95% CI, 0.04-0.71) and stage IIIB-IV (HR 0.16; 95% CI, 0.05-0.51). Further clinical studies are needed to improve the prognosis of patients with stage II-IV EMPD.

Artificial intelligence-based image-domain material decomposition in single-energy computed tomography for head and neck cancer.

PURPOSE: While dual-energy computed tomography (DECT) images provide clinically useful information than single-energy CT (SECT), SECT remains the most widely used CT system globally, and only a few institutions can use DECT. This study aimed to establish an artificial intelligence (AI)-based image-domain material decomposition technique using multiple keV-output learning of virtual monochromatic images (VMIs) to create DECT-equivalent images from SECT images. METHODS: This study involved 82 patients with head and neck cancer. Of these, the AI model was built with data from the 67 patients with only DECT scans, while 15 patients with both SECT and DECT scans were used for SECT testing. Our AI model generated VMI50keV and VMI100keV from VMI70keV equivalent to 120-kVp SECT images. We introduced a loss function for material density images (MDIs) in addition to the loss for VMIs. For comparison, we trained the same model with the loss for VMIs only. DECT-equivalent images were generated from SECT images and compared with the true DECT images. RESULTS: The prediction time was 5.4 s per patient. The proposed method with the MDI loss function quantitatively provided more accurate DECT-equivalent images than the model trained with the loss for VMIs only. Using real 120-kVp SECT images, the trained model produced precise DECT images of excellent quality. CONCLUSION: In this study, we developed an AI-based material decomposition approach for head and neck cancer patients by introducing the loss function for MDIs via multiple keV-output learning. Our results suggest the feasibility of AI-based image-domain material decomposition in a conventional SECT system without a DECT scanner.

Dose-volume comparisons of proton therapy for pencil beam scanning with and without multi-leaf collimator and passive scattering in patients with lung cancer.

This study evaluated the dose distributions of proton pencil beam scanning (PBS) with/without a multileaf collimator (MLC) compared to passive scattering (PS) for stage I/II lung cancers. Collimated/uncollimated (PBS+/PBS-) and PS plans were created for 20 patients. Internal-clinical-target-volumes (ICTVs) and planning-target-volumes (PTVs) with a 5 mm margin were defined on the gated CTs. Organs-at-risk (OARs) are defined as the normal lungs, spinal cord, esophagus, and heart. The prescribed dose was 66 Gy relative-biological-effectiveness (RBE) in 10 fractions at the isocenter and 50% volume of the ICTVs for the PS and PBS, respectively. We compared the target and OAR dose statistics from the dose volume histograms. The PBS+ group had a significantly better mean PTV conformity index than the PBS- and PS groups. The mean dose sparing for PBS+ was better than those for PBS- and PS. Only the normal lung doses of PBS- were worse than those of PS. The overall performance of the OAR sparing was in the order of PBS+, PBS-, and PS. The PBS+ plan showed significantly better target homogeneity and OAR sparing than the PBS- and PS plans. PBS requires collimating systems to treat lung cancers with the most OAR sparing while maintaining the target coverage.

Adverse events associated with postoperative outcomes of adjuvant anti-PD-1 antibody therapy in both acral and non-acral cutaneous melanomas: A multicenter, observational, post hoc analysis study.

Since anti-PD-1 Abs can cause irreversible immune-related adverse events (irAEs), the associations between their efficacies and the incidence of irAEs are important to evaluate the use of anti-PD-1Abs for the treatment of melanoma, especially in the adjuvant setting. The purpose of this post hoc analysis study was to retrospectively analyze the associations between recurrence-free survival (RFS) at 12 months and the onset of any irAEs in 31 non-acral cutaneous and 30 acral melanoma cases treated with anti-PD-1 Abs therapy at the adjuvant setting in Asians. There were 20 cases with greater than grade 1 AEs in both the acral and non-acral cutaneous groups. Of the acral melanoma, 10 cases were nails or toes, and 20 cases were soles and heels. The log-rank test showed that RFS was better in cases with AEs than in cases without AEs. The present study suggested that the different profiles of irAEs between non-acral cutaneous and acral melanoma might correlate with the different response to anti-PD1 Abs of melanoma in the adjuvant setting.

Impact of magnetic resonance imaging-related geometric distortion of dose distribution in fractionated stereotactic radiotherapy in patients with brain metastases.

PURPOSE: The geometric distortion related to magnetic resonance (MR) imaging in a diagnostic radiology (MRDR) and radiotherapy (MRRT) setup is evaluated, and the dosimetric impact of MR distortion on fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases is simulated. MATERIALS AND METHODS: An anthropomorphic skull phantom was scanned using a 1.5­T MR scanner, and the magnitude of MR distortion was calculated with (MRDR-DC and MRRT-DC) and without (MRDR-nDC and MRRT-nDC) distortion-correction algorithms. Automated noncoplanar volumetric modulated arc therapy (HyperArc, HA; Varian Medical Systems, Palo Alto, CA, USA) plans were generated for 53 patients with 186 brain metastases. The MR distortion at each gross tumor volume (GTV) was calculated using the distance between the center of the GTV and the MR image isocenter (MIC) and the quadratic regression curve derived from the phantom study (MRRT-DC and MRRT-nDC). Subsequently, the radiation isocenter of the HA plans was shifted according to the MR distortion at each GTV (HADC and HAnDC). RESULTS: The median MR distortions were approximately 0.1 mm when the distance from the MIC was < 30 mm, whereas the median distortion varied widely when the distance was > 60 mm (0.23, 0.47, 0.37, and 0.57 mm in MRDR-DC, MRDR-nDC, MRRT-DC, and MRRT-nDC, respectively). The dose to the 98% of the GTV volume (D98%) decreased as the distance from the MIC increased. In the HADC plans, the relative dose difference of D98% was less than 5% when the GTV was located within 70 mm from the MIC, whereas the underdose of GTV exceeded 5% when it was 48 mm (-26.5% at maximum) away from the MIC in the HAnDC plans. CONCLUSION: Use of a distortion-correction algorithm in the studied MR diagnoses is essential, and the dosimetric impact of MR distortion is not negligible, particularly for tumors located far away from the MIC.

Endobronchial spread of adenocarcinoma is a distinct pattern of invasion and associated with inferior clinical outcomes in lung adenocarcinoma.

AIM: The spread of lung adenocarcinoma cells into the bronchi and bronchioles is not well documented. We termed this histological finding "endobronchial spreading of adenocarcinoma" (EBSA) and investigated its prevalence and clinical significance. METHODS AND RESULTS: We reviewed 320 resected specimens from patients diagnosed with invasive adenocarcinoma, and EBSA was observed in 144 patients (45%). EBSA was significantly associated with advanced pathological stage, higher histological grade, larger tumour invasion, lymphovascular infiltration, and spread through air spaces. Patients with EBSA had significantly shorter relapse-free survival (RFS) and cancer-specific survival (CSS) in univariate analysis (P < 0.001). In a subgroup analysis of patient with small-sized (invasion size ≤30 mm) adenocarcinoma in the localized stage, EBSA was an independent inferior prognostic indicator in multivariate analysis. In a subgroup analysis of patients with small-sized Grade 1 nonmucinous adenocarcinoma (n = 61), EBSA was observed in 11 patients, and the presence of EBSA was associated with significantly shorter RFS and CSS (P = 0.026 and P = 0.001, respectively). CONCLUSION: Our results demonstrated that EBSA is a significant risk factor for disease recurrence and cancer-related deaths. EBSA can be regarded as a distinctive pattern of invasion and its recognition can be beneficial in the diagnosis of lung adenocarcinoma.

Patients with central serous chorioretinopathy have high circulating alpha-klotho concentrations.

Stress is a risk factor for central serous chorioretinopathy (CSC), but a suitable biomarker of this stress has not been identified. We aimed to evaluate alpha-klotho (αKl) as a potential biomarker of CSC. The circulating concentrations of αKl in patients diagnosed with acute or chronic CSC and treated at Hyogo College of Medicine between December 2019 and July 2021 were retrospectively compared with those of healthy individuals. We also compared the αKl concentrations of patients with acute or chronic CSC. Furthermore, we evaluated the relationships of age, sex, smoking status, and subfoveal choroidal thickness (SFCT) with αKl concentration. Patients in whom subretinal fluid reaccumulated in the same eye after its resolution were defined as having recurrent CSC. We studied 56 patients (46 men and 10 women) and 27 healthy controls (19 men and 8 women); and 38 and 18 eyes with acute and chronic CSC, respectively. The mean circulating concentration of αKl was higher in patients with CSC than in controls (827±232 and 724±183 pg/mL, respectively; p = 0.035). The mean SFCT was greater in patients with CSC than in controls (416±91.0 and 278±96.3 µm, respectively; p<0.0001). The mean αKl concentration was significantly higher in the patients with acute CSC than in those with chronic CSC (898±221 and 740±224 pg/mL, respectively; p = 0.038). Recurrence of CSC occurred in 10 of 56 (17.9%) eyes, of which five eyes were in the acute CSC group and five were in the chronic CSC group. Patients who experienced recurrence had significantly higher αKI concentrations than those who did not (p = 0.0219). There were no significant relationships of αKl concentration with age, sex, smoking history, or SFCT. In summary, the circulating αKI concentrations of patients with CSC are high, which suggests that αKI may be an indicator of stress in such patients.

Oral Microbial Profile Analysis in Patients with Oral and Pharyngeal Cancer Reveals That Tumoral Fusobacterium nucleatum Promotes Oral Cancer Progression by Activating YAP.

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles.

Expression of collagen-related piRNA is dysregulated in cultured dermal fibroblasts derived from patients with scleroderma.

PIWI-interacting RNA (piRNA) is a class of recently discovered small non-coding RNAs. piRNAs derive from an initial transcript encompassing a piRNA cluster via a unique biosynthesis process, interact with PIWI proteins, bind to specific targets, and recruit chromatin modifiers to enable transcriptional repression. Abnormal expression of PIWI proteins and piRNAs has been reported in some human cancers, with participation of some PIWI/piRNAs complexes in tumorigenesis and association with cancer prognosis. Their expression in patients with systemic sclerosis (SSc) has not been widely elucidated. PIWI/piRNAs and their role in the pathogenesis of collagen accumulation in SSc was therefore investigated; no difference was found in the PIWIL1-4 levels between normal and cultured SSc dermal fibroblasts. Among piRNAs predicted to target SSc-related molecules, we first found significant piR-32364 up-regulation in SSc dermal fibroblasts, likely due to intrinsic TGF-ß signaling. Forced piR-32364 overexpression in normal fibroblasts significantly reduced COL1A1 expression both at mRNA and protein levels, but not COL1A2. Thus, piR-32364 overexpression in SSc fibroblasts may be the negative feedback against collagen up-regulation, which could suggest the potential of piRNAs as a therapeutic target.

Effects of insulin-like growth factor-1 on the mRNA expression of estradiol receptors, steroidogenic enzymes, and steroid production in bovine follicles.

Insulin-like growth factor-1 (IGF-1) plays a crucial role in follicular growth and stimulates steroid hormone production in bovine follicles. Steroid hormones are synthesized through the actions of steroidogenic enzymes, specifically STAR, CYP11A1, HSD3B, and CYP19A1 in both theca cells (TCs) and granulosa cells (GCs), under the influence of gonadotropins. Particularly, estradiol 17ß (E2) assumes a central role in follicular development and selection by activating estrogen receptors ß (ESR2) in GCs. We assessed ESR2 mRNA expression in GCs of developing follicles and investigated the impact of IGF-1 on the mRNA expression of ESR2, CYP19A1, FSHR, and LHCGR, STAR, CYP11A1, and HSD17B in cultured GCs and TCs, respectively. Additionally, we assessed the influence of IGF-1 on androstenedione (A4), progesterone (P4), and testosterone (T) production in TCs. Small-sized follicles (< 6 mm) exhibited the highest levels of ESR2 mRNA expression, whereas medium-sized follicles (7-8 mm) displayed higher levels than large-sized follicles (≥ 9 mm) (P < 0.05). IGF-1 increased the mRNA expression of ESR2, CYP19A1, and FSHR in GCs of follicles of both sizes, except for FSHR mRNA in medium-sized follicles (P < 0.05). IGF-1 significantly elevated mRNA expression of LHCGR, STAR, CYP11A1, and CYP17B in TCs of small- and medium-sized follicles (P < 0.05). Moreover, IGF-1 augmented the production of A4 and P4 but had no impact on T production in TCs of small- and medium-sized follicles. Taken together, our findings indicate that IGF-1 upregulates steroidogenic enzymes and steroid hormone production, underscoring the crucial role of IGF-1 in follicle development and selection.

Assessment of the expression of microRNAs­221­3p, ­146a­5p, ­16­5p and BCL2 in oncocytic carcinoma of the breast: A case report.

Oncocytic carcinoma of the breast is rare and its molecular profiles remain poorly understood. MicroRNAs (miRNAs/miRs) have been identified as contributors to carcinogenesis at the post-transcriptional level; thus, an aberrant expression of miRNAs has attracted attention as a potential biomarker of numerous diseases, including cancer. The present study reports the case of a 76-year-old woman diagnosed with oncocytic carcinoma of the breast. Considering the distinctive feature of oncocytic carcinoma of the breast, which is the presence of granular eosinophilic cytoplasm containing numerous mitochondria, the present study hypothesized that the expression of mitochondria-related miRNAs could be altered in oncocytic carcinomas. Aberrant expression levels of the miRNAs previously reported as mitochondria-related miRNAs, such as miR-221-3p, -146a-5p and -16-5p, were revealed in tissue from specimens of oncocytic carcinoma of the breast, compared with that of a more typical type of invasive ductal carcinoma of the breast. The present study highlights the changes in miRNA expression in oncocytic carcinoma of the breast, suggesting its potential as a biomarker for diagnosis.