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13 pages, 1412 KB  
Article
Birth Type Lastingly Programs Secondary Hair Follicle Population and Cashmere Production in Cashmere Goats Despite Full Somatic Catch-Up Growth
by Kunjiang Li, Shaojie Wang, Zhenguo Wang, Xiujuan Jing, Zheqiao Zeng, Yanfang Shen, Guojing Jiang, Shuqi Liu, Chunxiang Zhang, Chunhe Yang and Youshe Ren
Animals 2026, 16(13), 2018; https://doi.org/10.3390/ani16132018 - 2 Jul 2026
Viewed by 163
Abstract
The objective of this study was to investigate the effects of birth type on growth performance, cashmere production traits, and hair follicle populations in cashmere goats. A total of 74 newborn kids (single, n = 38; twin, n = 36), all sired by [...] Read more.
The objective of this study was to investigate the effects of birth type on growth performance, cashmere production traits, and hair follicle populations in cashmere goats. A total of 74 newborn kids (single, n = 38; twin, n = 36), all sired by a single Inner Mongolian Cashmere buck, were used in this study. Body weights were recorded at birth, weaning, and yearling age to calculate pre- and post-weaning average daily gain (ADG). At yearling age, cashmere samples and skin biopsies were collected for measurement of cashmere yield, fiber diameter, staple length, and primary and secondary hair follicle population parameters. Results showed that single-born kids exhibited significantly greater birth weight by 18.3% (2.85 ± 0.06 kg vs. 2.41 ± 0.06 kg), weaning weight by 10.3% (20.17 ± 0.32 kg vs. 18.28 ± 0.17 kg), pre-weaning weight gain by 9.2% (17.31 ± 0.31 kg vs. 15.85 ± 0.20 kg), and pre-weaning ADG by 14.5% (146.5 ± 3.4 g vs. 127.9 ± 1.6 g) than twin-born kids (p < 0.05). Conversely, twin-born kids surpassed single-born kids in post-weaning weight gain by 14.4% (14.60 ± 0.48 kg vs. 12.76 ± 0.48 kg) and post-weaning ADG by 16.8% (60.5 ± 1.9 g vs. 51.8 ± 1.9 g), indicative of clear compensatory growth, resulting in no significant difference in yearling weight (32.90 ± 0.51 kg). Birth type significantly affected yearling cashmere production: single-born kids produced 10.1% more greasy cashmere (810 ± 22 g vs. 736 ± 28 g; p = 0.046) and exhibited a 0.45 μm finer mean fiber diameter (14.34 ± 0.10 μm vs. 14.79 ± 0.11 μm; p = 0.003), whereas staple length did not differ between groups (9.70 ± 0.12 cm). Consistent with the fiber trait results, no differences were detected in any primary hair follicle population parameters. By contrast, all secondary hair follicle traits were significantly higher in single-born goats, with secondary follicle density (SFD) being 10.6% greater (36.6 ± 1.0 vs. 33.1 ± 0.8; p = 0.010), secondary follicle density index 11.7% greater (363.9 ± 9.4 vs. 325.7 ± 7.6; p = 0.003), secondary follicle number 12.4% greater (33.46 ± 0.87 vs. 29.78 ± 0.70; p = 0.002), and the S/P ratio 8.9% greater (12.11 ± 0.36 vs. 11.12 ± 0.29; p = 0.041). All secondary follicle population parameters were negatively correlated with fiber diameter, among which SFD showed the strongest association (r = −0.70, p < 0.001). These findings indicate that birth type is associated with lasting differences in secondary hair follicle endowment and cashmere production, which persist at least through yearling age despite full compensatory body growth in twin-born kids. The observed association is consistent with the hypothesis that the pre-weaning period constitutes a critical window for follicle maturation—a window during which secondary follicle development is highly sensitive to nutritional status during gestation and early postnatal life. This suggests that targeted nutritional management of twin-bearing does during late gestation and early lactation may represent a promising strategy to partially mitigate the disadvantage in cashmere production potential imposed by twinning. However, direct causal evidence for both the developmental programming hypothesis and the efficacy of such nutritional interventions requires further experimental validation, including longer-term studies tracking animals across multiple production cycles and controlled nutritional trials. Full article
(This article belongs to the Section Small Ruminants)
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12 pages, 2707 KB  
Article
Oridonin Attenuates Cisplatin-Induced Ovarian Injury by Modulating Oxidative Stress, Inflammation, and TGF-β1/Smad3-Mediated Fibrosis in Rats
by Gulseren Dinc, Bakiye Akbas, Ahmet Akbas, Hatice Aygun and Oytun Erbas
Medicina 2026, 62(7), 1231; https://doi.org/10.3390/medicina62071231 - 25 Jun 2026
Viewed by 217
Abstract
Background and Objectives: The aim of this study is to evaluate the effects of oridonin on a cisplatin-induced ovarian injury rat model. Materials and Methods: Thirty female rats were divided into three groups. Group 1: control; group 2: cisplatin; group 3: [...] Read more.
Background and Objectives: The aim of this study is to evaluate the effects of oridonin on a cisplatin-induced ovarian injury rat model. Materials and Methods: Thirty female rats were divided into three groups. Group 1: control; group 2: cisplatin; group 3: cisplatin plus oridonin group. In groups 2 and 3, the rats were injected with 2.5 mg/kg (twice weekly) cisplatin intraperitoneally (i.p.) for 4 weeks. In Group 3, rats received oridonin (10 mg/kg/day, i.p.). At the end of the study, the ovaries were removed in all groups. Histopathologic analysis and follicle counting were performed. Plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels were measured, while ovarian transforming growth factor-beta 1 (TGF-β1), SMAD family member 3 (SMAD3), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels were evaluated. Results: Oridonin alleviated cisplatin-induced histopathological changes in the ovarian tissue. The numbers of primordial, primary, secondary, and tertiary follicles were significantly decreased, while ovarian fibrosis was significantly increased in Group 2 compared with Group 1 (p < 0.05). Co-treatment with oridonin statistically significantly increased follicle counts at all developmental stages and markedly reduced ovarian fibrosis in group 2 compared with group 3. Compared with Group 1, AMH decreased, whereas MDA, TNF-α, TGF-β1, SMAD3, and TIMP-1 increased in Group 2 (p < 0.001); these alterations were markedly attenuated in Group 3. Conclusions: These findings suggest that oridonin may exert protective effects against cisplatin-induced ovarian injury. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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16 pages, 1403 KB  
Review
Application of Anti-Müllerian Hormone in Regulation of Ovarian Function and Its Practical Relevance for Fertility and Embryo Production in Cows and Mares
by Andreas Vernunft and Dragos Scarlet
Vet. Sci. 2026, 13(6), 552; https://doi.org/10.3390/vetsci13060552 - 3 Jun 2026
Viewed by 1256
Abstract
In the female organism, Anti-Müllerian hormone (AMH) is produced exclusively by granulosa cells, particularly in secondary and early tertiary follicles. The amount of AMH released into the blood is proportional to the total number of follicles present in the ovaries and is therefore [...] Read more.
In the female organism, Anti-Müllerian hormone (AMH) is produced exclusively by granulosa cells, particularly in secondary and early tertiary follicles. The amount of AMH released into the blood is proportional to the total number of follicles present in the ovaries and is therefore used to estimate the ovarian functional reserve. In both cattle and mares, a strong and highly repeatable association has also been demonstrated between AMH concentrations and antral follicle count. Therefore, AMH may serve as a biomarker with broad diagnostic utility in reproductive medicine in these species, as it reflects the functional ovarian reserve through its association with viable antral and preantral follicles. While AMH is already being used for clinical diagnostics in human reproductive medicine and has been extensively investigated, it has received little attention in applied veterinary practice so far. This review explores the applications of AMH for reproductive medicine in cattle and horses, monoovulatory farm animals in which assisted reproductive technologies are widely used. The objectives of this review are to (I) provide clinically relevant background information and a comparative discussion of (II) the role of AMH in follicular development, (III) its value as a fertility indicator, and (IV) its significance for embryo production in vivo and in vitro in cows and mares, with particular emphasis on practical relevance and potential applications. Full article
(This article belongs to the Special Issue Advances in Animal Reproductive Biology and Technologies)
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20 pages, 4119 KB  
Article
Multiple-Dynamic-Bond Cross-Linked Injectable Antibacterial Hydrogel Sealants with Self-Healing for Wound Healing
by Tingting Wei, Yunrui Cao, Shuo Yang, Yu Song, Yanjun Liu, Hu Hou, Jie Xu and Changhu Xue
Gels 2026, 12(4), 340; https://doi.org/10.3390/gels12040340 - 19 Apr 2026
Viewed by 583
Abstract
Chronic wounds resulting from bacterial infection remain one of the main challenges in clinical practice. There is a pressing need to develop an injectable hydrogel sealant with multifunctional properties, including remodeling capabilities, self-healing, painless removal, and antibacterial activity, to promote tissue remodeling. In [...] Read more.
Chronic wounds resulting from bacterial infection remain one of the main challenges in clinical practice. There is a pressing need to develop an injectable hydrogel sealant with multifunctional properties, including remodeling capabilities, self-healing, painless removal, and antibacterial activity, to promote tissue remodeling. In this work, aldehyde carboxymethylated agarose (ACMA) is employed for the first time as a bio-template. Dopamine (DA) is introduced onto the ACMA template via a reversible Schiff-base reaction, endowing it with biomineralization properties to synthesize DA-modified ACMA-Ag nanoparticles (ACMA-DA-Ag). Further, the prepared ACMA-DA-Ag, which possesses both antibacterial activity and injectable behavior, is incorporated into a guar gum hydrogel through the formation of borate/diol bonds, thereby forming a multiple-dynamic-bond crosslinked network. This hydrogel demonstrates adequate mechanical strength, injectability, remodeling capabilities, and self-healing performance. It can reassemble into a new hydrogel within 4 ± 0.6 min upon simple physical contact, and supports tissue adhesion. Furthermore, the hydrogel effectively covers irregular-shaped wound and can be removed without causing secondary injury. More importantly, this multifunctional hydrogel is cost-effective, easy to synthesize, and simple to use, significantly accelerating skin regeneration and promoting the formation of skin appendages, such as hair follicles. The outcome of this research not only serves a tissue sealant for wound healing, but also presents a new strategy for creating novel polysaccharide-based biomaterials. Full article
(This article belongs to the Section Gel Chemistry and Physics)
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28 pages, 16544 KB  
Article
Ferulic Acid Alleviates Chemotherapy-Induced POI by Targeting the Grp78 and Perk-eIF2α-ATF4-CHOP Pathway to Attenuate Endoplasmic Reticulum Stress
by Fan Li, Yanjing Huang, Zhuo Liu, Yuli Geng, Runan Hu, Yufan Song, Lijun Xu and Mingmin Zhang
Biomedicines 2026, 14(3), 714; https://doi.org/10.3390/biomedicines14030714 - 19 Mar 2026
Cited by 1 | Viewed by 976
Abstract
Backgrounds: Premature ovarian insufficiency (POI) is a clinical syndrome characterized by premature ovarian dysfunction, amenorrhea, and infertility. Ferulic acid (FA) is a prominent bioactive phenolic compound derived from traditional Chinese herbs Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. These herbs are [...] Read more.
Backgrounds: Premature ovarian insufficiency (POI) is a clinical syndrome characterized by premature ovarian dysfunction, amenorrhea, and infertility. Ferulic acid (FA) is a prominent bioactive phenolic compound derived from traditional Chinese herbs Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. These herbs are commonly used to treat gynecological disorders including menstrual irregularities and infertility, and are known to modulate endoplasmic reticulum (ER) stress. However, the therapeutic potential and molecular mechanisms of FA in the context of POI remain largely unexplored. This study aimed to investigate the protective effects of FA against POI and to elucidate the underlying pharmacological mechanisms. Methods: In vivo, a mouse model of POI was established via a single intraperitoneal injection of cyclophosphamide (CTX; 120 mg/kg), and using FA for 28 days of continuous gavage to observe its therapeutic effect. Ovarian function and pathological changes were assessed by hormone levels, follicle development and oxidative stress (OS) level. In vitro, the effects of FA were examined using 4-hydroperoxy cyclophosphamide (4-OHCP)-treated KGN granulosa cells. Transcriptome sequencing, molecular docking, and molecular dynamics simulations were employed to identify potential targets of FA. Results: Our findings demonstrated that FA administration helped preserve regular estrous cycles, promoted follicle development and hormone secretion, and attenuated OS in both ovarian tissue and granulosa cells (GCs). Transcriptomic profiling combined with molecular docking and molecular dynamics simulations suggested that FA potentially targets key ER stress proteins, specifically Grp78 and Perk. Further in vivo and in vitro experiments confirmed that FA alleviates ER stress by inhibiting the overactivation of the Perk/eIF2α/ATF4/CHOP signaling pathway. Notably, the protective effects of FA were comparable to those of the ER stress inhibitor 4-Phenylbutyric acid (4-PBA) and were reversed by the ER stress activator tunicamycin (TM). Additionally, FA downregulates ERO1α expression, further blocking secondary oxidative damage triggered by ER stress. In KGN cells, FA significantly inhibits 4-OHCP-induced apoptosis and upregulates the anti-apoptotic proteins BCL-2 and BCL-xL, exhibiting efficacy similar to 4-PBA. Conclusions: FA improves ovarian function in CTX-induced POI by coordinately regulating OS and ER stress, inhibiting the Perk/eIF2α/ATF4/CHOP pathway, and suppressing GC apoptosis. These findings provide experimental evidence supporting FA as a potential therapeutic candidate for POI. Full article
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18 pages, 3419 KB  
Article
Comparative Skin Transcriptomics Reveals Key Regulators of Cashmere Fiber Production in Inner Mongolian Goats
by Hafiza Arooba Riaz, Muhammad Irfan Khan, Kiran Zahra, Rahmat Ali and Dejun Ji
Animals 2026, 16(6), 927; https://doi.org/10.3390/ani16060927 - 16 Mar 2026
Viewed by 1061
Abstract
Cashmere goats produce high-value fine fibers derived from secondary hair follicles; however, the molecular mechanisms underlying this trait remain incompletely understood. In this study, comparative transcriptome sequencing was performed on skin tissues from Inner Mongolian cashmere goats and normal goats to characterize gene [...] Read more.
Cashmere goats produce high-value fine fibers derived from secondary hair follicles; however, the molecular mechanisms underlying this trait remain incompletely understood. In this study, comparative transcriptome sequencing was performed on skin tissues from Inner Mongolian cashmere goats and normal goats to characterize gene expression differences associated with cashmere fiber production. High-quality RNA-seq data with strong mapping efficiency and reproducibility were obtained across all samples. Differential expression analysis identified 1543 significantly differentially expressed genes (DEGs) between cashmere and normal goats, including genes involved in hair follicle morphogenesis, epidermal differentiation, cell proliferation, and extracellular matrix organization. Multivariate analyses showed a clear transcriptomic separation between fleece types, indicating that fleece phenotype is the primary driver of variation in global gene expression. Functional enrichment revealed significant involvement of the Wnt, MAPK, and PI3K–Akt signaling pathways, and several biologically relevant regulators of hair follicle development and hair cycle control, including FGF5, SOX9, LHX2, and VDR, were differentially expressed. Gene fusion events were rare and showed no group specific patterns, whereas alternative splicing was widespread, with exon skipping as the predominant splicing event in goat skin. Overall, these results provide quantitative transcriptomic evidence linking signaling regulation, follicle development, and structural differentiation to secondary hair follicle activity and cashmere fiber formation, offering candidate genes and molecular pathways for functional validation and molecular breeding in cashmere goats. Full article
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22 pages, 2165 KB  
Article
Propolis Attenuates Cisplatin-Induced Ovarian Injury by Modulating Oxidative Stress, Inflammation, Apoptosis, and GRP78/ATF6/CHOP Pathway
by Bakiye Akbaş, Şeyda Kanbolat, Merve Badem, Oktay Yıldız, Mustafa Özgür Yalman, Engin Yenilmez and Rezzan Aliyazıcıoğlu
Curr. Issues Mol. Biol. 2026, 48(2), 212; https://doi.org/10.3390/cimb48020212 - 14 Feb 2026
Viewed by 880
Abstract
Cisplatin-induced ovarian damage is a significant concern for young women receiving chemotherapy. Although propolis, a polyphenol- and flavonoid-rich natural product, has been proposed as a protective agent, its effects on cisplatin-related ovarian injury remain insufficiently defined. This study aimed to investigate whether propolis [...] Read more.
Cisplatin-induced ovarian damage is a significant concern for young women receiving chemotherapy. Although propolis, a polyphenol- and flavonoid-rich natural product, has been proposed as a protective agent, its effects on cisplatin-related ovarian injury remain insufficiently defined. This study aimed to investigate whether propolis mitigates cisplatin-induced ovarian toxicity. In this study, 36 adult female Wistar rats were randomly allocated into six groups: Control, Propolis (50 mg/kg), Propolis (100 mg/kg), Cisplatin (7 mg/kg), Cisplatin + Propolis (50 mg/kg), and Cisplatin + Propolis (100 mg/kg). Cisplatin was administered as a single intraperitoneal dose on day 1, while propolis was given orally by gavage once daily for 14 days. Biochemical, histopathological, and endoplasmic reticulum (ER)-stress-related parameters were evaluated. Histopathologically, cisplatin caused significant vascular congestion, hemorrhage, edema, and follicular degeneration (p < 0.01), accompanied by marked reductions in primordial, primary, secondary, and tertiary follicle counts and a significant increase in atretic follicles. Propolis co-administration significantly ameliorated these lesions and partially preserved follicular counts, particularly at the 100 mg/kg dose (p < 0.01). Cisplatin markedly increased malondialdehyde (MDA) levels and ER stress markers (GRP78, ATF6, and CHOP), while reducing glutathione (GSH). Propolis treatment ameliorated these changes, decreased TNF-α and caspase-3 levels, and attenuated oxidative, inflammatory, and apoptotic responses. Propolis exerts strong antioxidant, anti-inflammatory, anti-apoptotic, and ER-stress-modulating effects that collectively counteract cisplatin-induced ovarian injury. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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17 pages, 747 KB  
Article
Minimal Dose Paradigm in IUI Stimulation for Unexplained Infertility: Letrozole-Initiated Late Gonadotropin Protocol
by Evren Yeşildağer, Ufuk Yeşildağer and Sefa Arlıer
J. Clin. Med. 2026, 15(3), 1050; https://doi.org/10.3390/jcm15031050 - 28 Jan 2026
Viewed by 1189
Abstract
Background: Optimizing pregnancy outcomes while minimizing gonadotropin exposure and treatment burden remains a major goal in ovulation induction for intrauterine insemination (IUI), particularly for patients with polycystic ovary syndrome (PCOS) or high ovarian reserve. Sequential protocols combining early letrozole with late-onset recombinant FSH [...] Read more.
Background: Optimizing pregnancy outcomes while minimizing gonadotropin exposure and treatment burden remains a major goal in ovulation induction for intrauterine insemination (IUI), particularly for patients with polycystic ovary syndrome (PCOS) or high ovarian reserve. Sequential protocols combining early letrozole with late-onset recombinant FSH (rFSH) have been proposed to enhance efficiency while reducing medication requirements. However, real-world comparative data adjusting for baseline differences are limited. Methods: This retrospective comparative cohort study included 764 IUI cycles performed between January 2022 and October 2025. Cycles were stimulated either with conventional rFSH (n = 372) or letrozole plus late-onset rFSH (n = 392). The primary outcome was pregnancy per cycle, defined by a positive serum β-hCG. Secondary outcomes included clinical pregnancy, total gonadotropin dose, endometrial thickness, cycle cancelation, and obstetric outcomes. Confounding was addressed using multivariable logistic regression, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and doubly robust estimation. Results: The crude pregnancy rate was higher in the letrozole plus late rFSH group compared with conventional rFSH (14.8% vs. 9.9%, p = 0.042). Women in the sequential stimulation group had higher AMH levels, higher antral follicle counts, and a higher prevalence of PCOS (32.4% vs. 16.3%, p = 0.001). After adjustment for age, ovarian reserve, and other baseline characteristics using regression, PSM, and IPTW, the stimulation protocol was not independently associated with pregnancy (adjusted OR 1.09, 95% CI 0.68–1.74; p = 0.657). Female age remained the strongest predictor of pregnancy (adjusted OR 0.70 per year increase; p < 0.001). The sequential protocol required a significantly lower total gonadotropin dose (median 375 IU vs. 750 IU; p < 0.001) while maintaining comparable cycle cancellation and safety outcomes. Conclusions: Sequential stimulation with letrozole plus late-onset rFSH achieves pregnancy outcomes comparable to conventional rFSH stimulation while significantly reducing gonadotropin requirements. After adjustment for PCOS status and ovarian reserve, the protocol itself did not independently influence pregnancy, suggesting that crude differences reflected baseline imbalances rather than true treatment effects. This approach represents a clinically efficient, gonadotropin-sparing option for IUI, particularly in patients at risk for excessive ovarian response. Full article
(This article belongs to the Special Issue Female Infertility: Clinical Diagnosis and Treatment—Second Edition)
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10 pages, 1044 KB  
Article
Molecular Regulation of Secondary Hair Follicle Stem Cell by S100a4 in Cashmere Goat
by Xinyue Liang, Bohan Liu, Jiayi Wang, Yanlei Liu, Yiping Wei, Hongji Yu, Junpeng Zhang, Shuyi Zhang and Huiling Xue
Int. J. Mol. Sci. 2026, 27(2), 849; https://doi.org/10.3390/ijms27020849 - 15 Jan 2026
Viewed by 728
Abstract
Secondary hair follicle stem cells (HFSCs) are essential for cashmere fiber regeneration, yet the molecular mechanisms governing their activation and lineage progression remain poorly understood. Here, we identify S100a4 as a key regulator of secondary HFSCs in cashmere goat. S100a4 expression peaks during [...] Read more.
Secondary hair follicle stem cells (HFSCs) are essential for cashmere fiber regeneration, yet the molecular mechanisms governing their activation and lineage progression remain poorly understood. Here, we identify S100a4 as a key regulator of secondary HFSCs in cashmere goat. S100a4 expression peaks during anagen and is markedly enriched in secondary HFSCs relative to hair matrix cells (HMCs), suggesting a role in initiating follicle regeneration. Functional assays show that S100a4 promotes HFSCs into a dynamically regulated state that activates stem cell competence while facilitating differentiation, with overexpression upregulating epidermal and follicular differentiation markers (Ivl, Cux1, K14, Klk5), as well as pluripotency genes (Itga6, Krt15), while knockdown suppresses these programs. Proteomic analysis further reveals direct interactions between S100A4 and keratins critical for hair follicle and epidermal development (KRT5, KRT14, KRT8, KRT18), suggesting a structural and regulatory interface through which S100A4 modulates HFSC fate. Collectively, these results establish S100a4 as a central modulator of secondary HFSC function and provide mechanistic insight into the molecular control of hair follicle regeneration, with potential implications for improving cashmere fiber production. Full article
(This article belongs to the Special Issue Molecular Insights into Zoology)
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14 pages, 5733 KB  
Article
Immunohistochemical Pattern of CD34 Distribution in Different Types of Basal Cell Carcinoma and in Peritumoral Skin
by Vladimir Petrovic, Aleksandar Petrovic, Ivan R. Nikolic, Nataša Vidovic, Tijana Dencic, Ilija Golubovic, Miroslav Milic and Aleksandra Antovic
Medicina 2026, 62(1), 158; https://doi.org/10.3390/medicina62010158 - 13 Jan 2026
Viewed by 1710
Abstract
Background and Objectives: Basal cell carcinoma (BCC) is the most common skin carcinoma, mainly occurring in older individuals. The aim of this study was to document the immunohistochemical distribution of CD34 in different histopathological types of BCC, as well as in the [...] Read more.
Background and Objectives: Basal cell carcinoma (BCC) is the most common skin carcinoma, mainly occurring in older individuals. The aim of this study was to document the immunohistochemical distribution of CD34 in different histopathological types of BCC, as well as in the peritumoral and uninvolved skin of biopsy samples. Materials and Methods: Excisional biopsies of skin BCCs were routinely processed into paraffin blocks, and microtome sections were stained immunohistochemically for CD34. Results: A consistent finding in skin samples containing BCC was the absence of CD34 in the following extravascular structures: neoplastic cells, epidermis and its derivatives (except for the cells of the isthmic part of the outer hair follicle sheath), fibroblast-like cells of BCC tumor stroma, as well as in the papillary dermis in the tumor region. Fibroblast-like cells of the tumor stroma were variably CD34 immunopositive only in the nodular type of BCC. In all examined biopsies, part of the dermis adjacent to the BCC tumor mass (juxtatumoral zone) was characterized by pronounced CD34 immunopositivity. In the transitional zone of peritumoral skin and in marginal skin, CD34-positive connective tissue cells were observed in the periadnexal dermis around: sebaceous gland lobules, the secretory coils of eccrine sweat glands, the pilosebaceous canal, as well as in the perimysium of the arrector pili muscle. Fibrocytes of fibrous sheaths encasing the isthmic part of hair follicles were CD34 negative, interposed between highly positive epithelial cells of the outer hair follicle sheath and the fibroblasts of the local reticular dermis. The transitional zone and uninvolved skin contained CD34-positive fibroblast-like cells situated between secondary bundles of reticular dermis, as well as CD34-positive cell processes within these bundles. Conclusions: The observed pattern of CD34 positivity within the examined regions shows a specific distribution, providing insight into the adaptive responses of the skin to the tumoral process. Full article
(This article belongs to the Section Oncology)
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10 pages, 493 KB  
Article
Does the Immunohistotype of Breast Cancer Influence Ovarian Reserve and Fertility Preservation Outcomes? A Single-Center Prospective Observational Study
by Valentina Immediata, Sabrina Aprea, Emanuela Morenghi, Annamaria Baggiani, Cristina Specchia, Damiano Gentile, Corrado Tinterri and Paolo Emanuele Levi-Setti
Cancers 2025, 17(21), 3564; https://doi.org/10.3390/cancers17213564 - 3 Nov 2025
Cited by 1 | Viewed by 929
Abstract
Background: Breast cancer (BC) in reproductive-age women raises concerns about fertility preservation, particularly as systemic therapies may compromise ovarian function. Evidence on whether tumor immunohistotype influences ovarian reserve and fertility preservation outcomes remains limited. Methods: We conducted a prospective cohort study of BC [...] Read more.
Background: Breast cancer (BC) in reproductive-age women raises concerns about fertility preservation, particularly as systemic therapies may compromise ovarian function. Evidence on whether tumor immunohistotype influences ovarian reserve and fertility preservation outcomes remains limited. Methods: We conducted a prospective cohort study of BC patients referred for fertility preservation counseling between November 2020 and May 2025. Ovarian reserve was assessed using anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). Controlled ovarian stimulation (COS) and oocyte cryopreservation were performed according to standardized protocols. Patients were stratified into triple-negative BC (TNBC) and hormone receptor-positive (HR+) and/or HER2+ groups. The primary endpoint was ovarian reserve differences by subtype; the secondary endpoints were ovarian response and oocyte yield. Results: Of 358 patients, 152 were enrolled, and 139 (91.4%) underwent COS, for a total of 145 cycles. The median age was 33 years, median AMH 5.4 ng/mL, and median AFC 17. No significant differences were observed between the TNBC and HR+/HER2+ groups in AMH, AFC, oocyte yield, or mature oocyte rate. Sub-analysis revealed a significantly lower mature oocyte yield in luminal-B tumors. Conclusions: Ovarian reserve and cryopreservation outcomes appeared preserved in TNBC compared with those in patients with HR+/HER2+ BC at diagnosis. These findings provide reassurance that baseline fertility potential is not compromised by tumor immunohistotype. Full article
(This article belongs to the Special Issue Research on Early-Stage Breast Cancer: Management and Treatment)
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17 pages, 4614 KB  
Article
Screening of circRNAs Associated with Secondary Wool Follicle Development in Fine-Wool Sheep and Construction of Their ceRNA Network
by Yu Luo, Binpeng Xi, Yufang Song, Tong Xiao, Zengkui Lu, Jianbin Liu, Chao Yuan and Tingting Guo
Animals 2025, 15(17), 2629; https://doi.org/10.3390/ani15172629 - 8 Sep 2025
Viewed by 1186
Abstract
Various signalling molecules and pathways critical for wool production and quality regulate wool secondary follicle (SF) development. Circular RNAs (circRNAs) regulate SF morphogenesis through a competing endogenous RNA (ceRNA) mechanism; these novel cyclic non-coding RNAs are not known to regulate the development of [...] Read more.
Various signalling molecules and pathways critical for wool production and quality regulate wool secondary follicle (SF) development. Circular RNAs (circRNAs) regulate SF morphogenesis through a competing endogenous RNA (ceRNA) mechanism; these novel cyclic non-coding RNAs are not known to regulate the development of SFs in the foetal period of fine-wool sheep. Here, we analysed circRNA expression profiles in the foetal skin of Gansu Alpine fine-wool sheep at 10 developmental stages (E87, E90, E93, E96, E99, E102, E105, E108, E111, and E138) using RNA sequencing. Among the differentially expressed circRNAs (DE circRNAs), 173 were significantly enriched in signalling pathways related to hair follicle (HF) development, such as Wnt/β-catenin, transforming growth factor-β/Smad, Notch, and mitogen-activated protein kinase. Six HF-development-related circRNAs were expressed at different stages and potentially regulated SF development through the ceRNA network. In total, 16 DE circRNAs and their targets, 44 miRNAs, and 65 mRNAs were screened, and 88 ceRNA regulatory network pathways related to SF development were constructed. These key DE circRNAs could be candidate genes for further exploration of the molecular HF development mechanism, providing an important theoretical basis for unravelling the regulatory network of SF development in fine-wool sheep and genetic wool trait improvement. Full article
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18 pages, 2265 KB  
Article
Krill Oil Mitigates Cisplatin-Induced Ovarian Toxicity via Attenuation of Oxidative Stress and Inflammatory Pathways
by Erson Aksu and Oytun Erbas
Curr. Issues Mol. Biol. 2025, 47(9), 708; https://doi.org/10.3390/cimb47090708 - 1 Sep 2025
Cited by 3 | Viewed by 1859
Abstract
Cisplatin remains a cornerstone chemotherapeutic agent; however, its off-target gonadotoxicity poses a significant risk for premature ovarian failure (POF) and infertility in young women. Strategies to preserve ovarian function during chemotherapy are critically needed. To investigate the protective effects of krill oil supplementation [...] Read more.
Cisplatin remains a cornerstone chemotherapeutic agent; however, its off-target gonadotoxicity poses a significant risk for premature ovarian failure (POF) and infertility in young women. Strategies to preserve ovarian function during chemotherapy are critically needed. To investigate the protective effects of krill oil supplementation against cisplatin-induced ovarian damage in a rat model, with a focus on oxidative stress, inflammation, follicular dynamics, and stromal fibrosis. Twenty-one adult female Wistar albino rats were randomized into three groups: control, cisplatin-treated, and cisplatin + krill oil-treated. Ovarian toxicity was induced via intraperitoneal injection of cisplatin (2.5 mg/kg, twice weekly for four weeks). Krill oil (4 mL/kg/day) was administered orally during the same period. Ovarian histopathology, follicle counts (primordial, primary, secondary, tertiary), stromal fibrosis, and biochemical markers, including plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and ovarian levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Toll-like receptor 4 (TLR4), TNF-α, NOD-like receptor family pyrin domain containing 3 (NLRP3), and IL-1β were evaluated. Cisplatin significantly reduced primordial, primary, secondary, and tertiary follicle counts while increasing stromal fibrosis (p < 0.001). Krill oil co-treatment notably ameliorated follicular depletion—improving follicle counts by 38.16%, 54.74%, 62.5%, 40.43%, respectively—and reduced fibrosis (p = 0.017). Biochemically, cisplatin decreased AMH levels and Nrf2 expression while elevating MDA, TNF-α, TLR4, NLRP3, and IL-1β levels (p < 0.001). Krill oil supplementation restored AMH (p = 0.002) and Nrf2 (p = 0.003) levels, while reducing MDA (p = 0.009), NLRP3 (p < 0.001), ovarian IL-1β (p = 0.005), plasma IL-1β (p < 0.001), TLR4 (p = 0.001), plasma TNF-α (p = 0.001), and ovarian TNF-α (p < 0.001), compared to the cisplatin group. Krill oil exerts significant antioxidant and anti-inflammatory effects, offering a promising strategy to mitigate cisplatin-induced ovarian damage and preserve fertility in young cancer patients. Full article
(This article belongs to the Section Molecular Medicine)
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16 pages, 8469 KB  
Case Report
IgG4-Mediated Sclerosing Riedel Thyroiditis: A Multidisciplinary Case Study and Literature Review
by Dumitru Ioachim, Mihai Alin Publik, Dana Terzea, Carmen Adina Cristea, Adina Mariana Ghemigian, Anda Dumitrascu, Eugenia Petrova, Alexandra Voinea, Romeo Smarandache and Mihail Ceausu
Int. J. Mol. Sci. 2025, 26(16), 7786; https://doi.org/10.3390/ijms26167786 - 12 Aug 2025
Cited by 3 | Viewed by 2472
Abstract
Riedel thyroiditis (RT) is a rare immune-mediated inflammatory disease that destroys the thyroid parenchyma, replacing it with storiform fibrosis extending to the extrathyroidal tissue. Secondary fibrotic lesions can be associated as parts of the systemic IgG4-related disease. We present the case of a [...] Read more.
Riedel thyroiditis (RT) is a rare immune-mediated inflammatory disease that destroys the thyroid parenchyma, replacing it with storiform fibrosis extending to the extrathyroidal tissue. Secondary fibrotic lesions can be associated as parts of the systemic IgG4-related disease. We present the case of a 52-year-old female patient who presented initially with subacute thyroiditis when corticosteroid treatment was initiated. After a year, compressive respiratory symptoms and dysphagia appear, and fine-needle aspiration cytology is performed to rule out malignancy, but without results. Thyroidectomy is performed, and histopathology shows scleroatrophic thyroiditis, with chronic inflammatory infiltrate containing eosinophils extending in the neighboring tissue, rare atrophic follicles, and obliterative vasculitis. Immunohistochemistry proves abundant plasma cells with IgG4 secretion; the macrophage is mainly the M2 subtype. RT is diagnosed, and a CT (computed tomography) scan is performed to detect peritracheal fibrosis and subtle pulmonary modifications. A literature review was performed that situates our findings in the context of the current literature. The last part discusses the immuno-inflammatory mechanisms behind IgG4-related diseases. Full article
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11 pages, 796 KB  
Case Report
The Double-Edged Nature of the Gonadotropin-Releasing Hormone Agonist (GnRHa) Long Protocol: A Case of Paradoxical Ovarian Hyperstimulation During the Expected Downregulation Phase
by Bernadett Nádasdi, Péter Kovács, Éva Adrienn Csajbók, Károly Wellinger, Anna Vágvölgyi and János Zádori
J. Clin. Med. 2025, 14(14), 4992; https://doi.org/10.3390/jcm14144992 - 15 Jul 2025
Viewed by 2490
Abstract
Objectives: Our aim is to report an uncommon pituitary activation occurring during the desensitization phase of the gonadotropin-releasing hormone agonist (GnRHa) long protocol, a cornerstone of medically assisted reproduction (MAR) therapy, in a young woman. Results: We present a case of [...] Read more.
Objectives: Our aim is to report an uncommon pituitary activation occurring during the desensitization phase of the gonadotropin-releasing hormone agonist (GnRHa) long protocol, a cornerstone of medically assisted reproduction (MAR) therapy, in a young woman. Results: We present a case of a 33-year-old female patient with secondary infertility, who exhibited a prolonged and asynchronous follicular development during ovarian stimulation using the GnRH antagonist protocol. Therefore, during a repeat attempt, the long GnRH agonist protocol was employed. Surprisingly, rather than achieving suppression with the agonist, ultrasound detected many large follicles in both ovaries, accompanied by extremely elevated estrogen levels, indicating imminent ovarian hyperstimulation syndrome (OHSS). This unusual phenomenon was also observed during a subsequent attempt using the long protocol in another reproductive center. As part of the work-up to identify the underlying etiology, contrast-enhanced magnetic resonance imaging (MRI) of the sella turcica was performed, which revealed an 11 × 13 × 10 mm pituitary macroadenoma without evidence of pathological hormone secretion. The luteinizing hormone-releasing hormone (LHRH) stimulation test showed a normal luteinizing hormone and follicle-stimulating hormone response. Other abnormalities of the hypothalamo–hypophyseal–target-organ axis were not found. Neurosurgical intervention was deemed unnecessary; radiological follow-up of the lesion was recommended. Conclusions: In this case, the clinical presentation was markedly different from the expected suppressive effects of GnRH agonist therapy, with profoundly elevated estrogen levels and clinical signs of imminent OHSS. Notably, hypersensitivity of the adenohypophysis was not demonstrated following a single physiological LHRH stimulation test. However, the presence of a pituitary adenoma identified on MRI raises the possibility that gonadotropin receptor function was altered by the lesion—an effect revealed only after repeated GnRH agonist exposure, resulting in a paradoxical stimulatory response. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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