Atrophy Of Follicles Research Articles

Near-infrared light-triggered nitric oxide-releasing hyaluronic acid hydrogel for precision transdermal therapy of androgenic alopecia.

Progressive follicle and vascular atrophy, insufficient nutrient supply, and hormonal imbalance are direct causes of androgenic alopecia (AGA), limiting treatment options. Nitric oxide (NO) has demonstrated significant advantages in cell proliferation, vascular repair, and inflammation regulation. However, precise control of NO concentration and efficient utilization limit its clinical application for AGA treatment. To address this, we developed a near-infrared (NIR) light-triggered NO-releasing delivery system (Gel@L-Arg). The system uses Chlorin e6 (Ce6) grafted onto oxidized hyaluronic acid, reacting with L-Arg-loaded polyethyleneimine via Schiff base to form hyaluronic acid hydrogel. Under NIR light, Ce6 generates ROS, oxidizing L-Arg to release NO, after 5 min of irradiation, the NO concentration in Gel@L-Arg (1 %) is >1.5 times that in Gel@L-Arg (0.5 %), enabling on-demand release of NO. Gel@L-Arg (0.5 %) effectively promotes angiogenesis while significantly repairing damaged human dermal papilla cells (HDPCs), with cell viability reaching 131.6 ± 4.6 %. In animal models, the system reduced inflammation (IL-6, TNF-α), enhanced nutrient supply (VEGF, CD31), regulated androgens, and improved the follicular microenvironment, effectively treating AGA. This hyaluronic acid hydrogel, combining NIR light-triggered release with gas therapy, offers a new strategy for the treatment of AGA with good biocompatibility, providing insight into controlled gas release therapies for disease treatment.

MiR-302c-3p regulates autophagy and apoptosis in ovarian granulosa cells via the LATS2/YAP axis in chickens

The degenerative process of follicular atresia in hens naturally commences in granulosa cells, significantly impacting laying hens' reproductive performance. Past studies suggested that granulosa cell autophagy and apoptosis work together to cause follicular atresia. Recent research indicates that miRNA regulates granulosa autophagy and apoptosis, which contributes to the development of follicular atresia. However, the role of miR-302c-3p in follicular atresia and development remains unclear. In this study with the RNA-seq approach, we found that miR-302c-3p expression was significantly decreased in atrophic follicles, suggesting its involvement in the follicular atresia process. Following this, we performed in vitro studies to confirm that miR-302c-3p inhibits autophagy and apoptosis in chicken granulosa cells. Mechanistically, LATS2 is considered as the putative target gene of miR-302c-3p, and it has been demonstrated that LATS2 exerts a positive regulatory role in the modulation of autophagy and apoptosis in chicken granulosa cells. Furthermore, we verified the regulatory function of miR-302c-3p in chicken granulosa cells via the LATS2-YAP signaling pathway. Our results collectively demonstrates that miR-302c-3p targets LATS2 to modulate the YAP signaling pathway, impacting autophagy and apoptosis in granulosa cells leading to follicular atresia.

USP13 regulates ferroptosis in chicken follicle granulosa cells by deubiquitinating ATG7

The development and maturation of follicles are intricately linked to egg production and reproductive performance of chickens. Granulosa cells death directly affects the development and maturation of follicles, thereby impacting the reproductive performance of hens. Ferroptosis is a new type of cell death, it is unknown how it affects the growth and development of chicken follicles. In this study, RNA-seq analysis revealed significant differences in the expression of ferroptosis-related genes between normal follicles and atretic follicles, suggesting a potential role for ferroptosis in follicle growth and development. In addition, we found that ubiquitin-specific protease 13 (USP13) was significantly upregulated in atrophic follicles. Overexpression of USP13 results in depletion of glutathione (GSH), peroxidation of lipids, accumulation of iron, and activation of ferroptosis in chicken granulosa cells. In contrast, USP13 knockdown significantly inhibited ferroptosis events. Mechanistically, USP13 prevents the degradation of autophagy related 7 (ATG7) by deubiquitinating it, thereby enhancing the stability of ATG7 protein and ultimately promoting ferroptosis. In conclusion, this study elucidates the crucial role of the USP13-ATG7 axis in regulating ferroptosis in chicken follicle granulosa cells, thereby presenting a novel avenue for molecular breeding research in chickens.

Clinical and pathologic characterization of African swine fever virus infection in pigs in the Mekong Delta, Vietnam

African swine fever (ASF) is a highly infectious disease in pigs caused by the African swine fever virus (ASFV), which might result in 100% mortality. Pigs infected with ASFV might display different clinical and pathological features depending on virulence and host factors. This study aimed to determine features of clinical symptoms, macroscopic, and microscopic lesions of ASF in the Mekong Delta (MD), Vietnam during 2021–2022. The investigation was conducted following three fatal outbreaks of ASF in Hau Giang, Vinh Long, and Can Tho provinces, which are three central provinces out of thirteen in the MD. The spleen, lymph nodes, liver, kidney, and heart were collected from three infected pigs that displayed clinical symptoms of ASFV infection and confirmed the presence of ASFV by conventional PCR. The results indicated that infected pigs showed common clinical symptoms including high fever, anorexia, and moderate petechiae on the skin. Severe hemorrhage was observed in lymph nodes, spleen, kidneys, intestines, and gallbladders which were the main lesions during post-mortem examination. Microscopic lesions were characterized by lymphocytopenia, atrophy of lymphoid follicles in the immune system. However, distinct variations in clinical symptoms, macroscopic, and microscopic features among ASFV infection cases were not documented. This study provides a further understanding of the clinical presentation and pathological lesions caused by the ASFV strain circulating in the MD.

Histopathological and Immunohistochemical Studies on Endocrine Glands of Dogs with Special Emphasis on the Immunoexpression of β-cells of the Pancreas

The aim of this study to evaluate the histopathological, histochemical and immunohistochemical changes of the endocrine glands namely, thyroid, pancreas and adrenal gland in dogs submitted to routine necropsy. A total number of 45 endocrine samples were collected from 15 carcasses of dogs received at Department of Veterinary Pathology, Madras Veterinary College, Chennai- 600 007 were chosen for the present study, namely thyroid, pancreas and adrenal gland. The tissue samples were collected in 10% neutral buffered formalin. Tissues were processed after 48 hours as per recommended procedure and 3 µm thickness sections were made and stained with haematoxylin and eosin for histopathological evaluation. The special stains like Masson’s trichrome and Picrosirius red were used to assess the extent of replacement with collagen fibers. Immunohistochmical protocol was followed as per the manufactured recommendation (Pathnsitu, USA).The histopathological changes recorded in the pancreas included vacuolar changes (2/15), necrosis (2/15), periductular fibrosis (1/15), perivascular fibrosis (1/15), congestion (5/15), hemorrhages (3/15) and inflammatory changes (1/15) while in the adrenal glands included diffuse cortical hyperplasia (4/15) succeeded by nodular hyperplasia (3/15), adrenalitis (2/15), hyperaemia (2/15), hemorrhages (1/15) and atrophy (1/15). Histopathological examination of thyroid revealed atrophy of follicles suggesting thyroiditis (3/15), presence of follicular epithelial cells which were found separated from the basement membrane with cellular debris in the lumen indicating necrosis (2/15) and presence of large cystic gaps with eosinophilic proteinaceous material consistent with cystadenoma(2/15). The remaining samples showed hemorrhages (2/15), perivascular fibrosis (1/15) and congestion (2/15). However no histological alterations were noticed in 3 cases (3/15). Immunohistochemistry revealed that pancytokeratin was expressed by all epithelial cells including ducts. The expression of insulin was noticed in all the cases indicating that no reduction of â cells in all the above said pathological conditions.

CircRAB11A act as miR-24-5p sponge promotes proliferation and resists apoptosis of chicken granulosa cell via EGFR/ERK1/2 and RAB11A/ PI3K/AKT pathways

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs that have been implicated in mediating granulosa cell (GC) proliferation and apoptosis. CircRAB11A was found to have a significantly higher expression in normal follicles compared to atrophic follicles. In this study, we determined that the knockdown of circRAB11A resulted in the inhibition of proliferation and promotion of apoptosis in GCs of chicken. Moreover, circRAB11A was found to act as a sponge for miR-24-5p, both member RAS oncogene family (RAB11A) and epidermal growth factor receptor (EGFR) were revealed to be targets of miR-24-5p through a dual-luciferase reporter assay. RAB11A or EGFR promoted proliferation and suppressed apoptosis in GCs through the phosphatidylinositol-kinase (PI3K)/AKT or extracellular signal-regulated kinase (ERK)1/2 pathway. These findings suggest that circRAB11A may function as a competing endogenous RNA (ceRNA) by targeting the miR-24-5p/RAB11A and miR-24-5p/EGFR axes and activating the ERK1/2 and PI3K/AKT pathways, offering a potential avenue for exploring the mechanism of follicle development.

β-Nicotinamide Mononucleotide Promotes Cell Proliferation and Hair Growth by Reducing Oxidative Stress.

β-Nicotinamide mononucleotide (NMN) has shown promising effects on intestinal health, and it is extensively applied as an anti-aging and Alzheimer's disease therapeutic, due to its medicinal properties. The effects of NMN on the growth of mouse hair were observed after hair removal. The results indicated that NMN can reverse the state of hair follicle atrophy, hair thinning, and hair sparsity induced by dihydrotestosterone (DHT), compared to that of minoxidil. In addition, the action mechanisms of NMN promoting hair growth in cultured human dermal papilla cells (HDPCs) treated with DHT were investigated in detail. The incubation of HDPCs with DHT led to a decrease in cell viability and the release of inflammatory mediators, including interleukin-6 (IL-6), interleukin-1Beta (IL-1β) and tumor necrosis factor Alpha (TNF-α). It was found that NMN can significantly lower the release of inflammatory factors induced by DHT in HDPCs. HDPCs cells are protected from oxidative stress damage by NMN, which inhibits the NF-κB p65 inflammatory signaling pathway. Moreover, the levels of androgen receptor (AR), dickkopf-1 (DKK-1), and β-catenin in the HDPCs were assessed using PCR, indicating that NMN can significantly enhance the expression of VEGF, reduced IL-6 levels and suppress the expression of AR and DKK-1, and notably increase β-catenin expression in DHT-induced HDPCs.

Experimental rat models for Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease characterized by T lymphocyte-mediated destruction of thyroid follicles. To study the pathogenesis of HT and the efficacy of new substances for its treatment, an easily obtained and adequate to the human disease experimental model is needed. The aim of our study was to find out whether it is possible to induce experimental autoimmune thyroiditis (EAT) similar to Hashimoto's thyroiditis by injecting with thyroglobulin (Tg) without using agents that enhance its thyroiditogenicity and without taking into account the genetic sensitivity of animals. Wistar rats were immunized with freshly isolated rat Tg or porcine Tg. In 8weeks, histological studies of the thyroid and parathyroid glands were performed. Thyroid function and total serum calcium level were also evaluated. Immunization with both rat and porcine freshly isolated Tg caused T lymphocytic infiltration of the thyroid gland, thyroid follicle atrophy and degradation in Wistar rats. EAT caused by porcine Tg was characterized by greater severity than EAT induced with rat Tg. In 55% of rats with porcine Tg-induced EAT, oxyphilic metaplasia was detected in the parathyroid glands. In addition, low total serum calcium was observed in these rats. Two rat models of autoimmune thyroiditis were obtained. EAT caused in Wistar rats by immunization with rat Tg is similar to Hashimoto's thyroiditis. EAT induced with porcine Tg was accompanied by oxyphil cell metaplasia in the parathyroids and hypocalcemia.

MiRNA-29-3p targets PTEN to regulate follicular development through the PI3K/Akt/mTOR signaling pathway

Granulosa cells play a pivotal role in growth, development and ovulation of ovarian follicle. Simultaneously, autophagy and apoptosis processes are crucial determinants in the destiny of granulosa cells. Within this context, miR-29-3p, known to regulate a broad spectrum of biological processes and critical for tumor detection, prognosis, and treatment, is poised to clarify its roles in both autophagy and apoptosis. To enhance the understanding of the influence of miR-29-3p on follicular development, our study primarily delved into the realms autophagy and apoptosis. We employed a well-established chicken follicular atrophy model achieved through subcutaneous injection of tamoxifen (TMX) into hens. qPCR analysis revealed a significant decrease in the expression of miR-29-3p within the atrophic follicles. In our in vitro experiments with cultured chicken primary granulosa cells, miR-29-3p emerged as a novel microRNA capable of impeding autophagy and apoptosis when transfected with miR-29-3p mimics and inhibitors. Results from luciferase reporter assays corroborated that PTEN is a legitimate target of miR-29-3p. Unlike miR-29-3p, PTEN appeared to foster autophagy and apoptosis in chicken granulosa cells. Moreover, our findings uncovered that miR-29-3p facilitates the phosphorylation of Akt and mTOR proteins by targeting PTEN in chicken granulosa cells. In conclusion, the findings of this study suggest that miR-29-3p, through its targeting of PTEN via the Akt/mTOR signaling pathway, exerts inhibitory effects on autophagy and apoptosis. These effects may hold significant importance in the context of follicular development.

Immunomodulatory Effects of Histone Variant H2A.J in Ionizing Radiation Dermatitis

Histone variant H2A.J is associated with premature senescence after ionizing radiation (IR) and modulates senescence-associated secretory phenotype (SASP). Using constitutive H2A.J knock-out mice, the role of H2A.J was investigated in radiation dermatitis. H2A.J wild-type (WT) and knock-out (KO) mice were exposed to moderate or high IR doses (≤20 Gy, skinfold IR). Radiation-induced skin reactions were investigated up to 2 weeks post-IR at macroscopic and microscopic levels. H2A.J and other senescence markers, as well as DNA damage and proliferation markers, were studied by immunohistochemistry, immunofluorescence, and electron microscopy. After high-dose IR, protein-coding transcriptomes were analyzed by RNA sequencing, immune cell infiltration by flow cytometry, and gene expression by reverse transcription polymerase chain reaction in (non-) irradiated WT versus KO skin. In WT skin, epidermal keratinocytes showed time- and dose-dependent H2A.J accumulation after IR exposure. Unexpectedly, stronger inflammatory reactions with increased epidermal thickness and progressive hair follicle loss were observed in irradiated KO versus WT skin. Clearly more radiation-induced senescence was observed in keratinocyte populations of KO skin after moderate and high doses, with hair follicle stem cells being particularly badly damaged, leading to follicle atrophy. After high-dose IR, transcriptomic analysis revealed enhanced senescence-associated signatures in irradiated KO skin, with intensified release of SASP factors. Flow cytometric analysis indicated increased immune cell infiltration in both WT and KO skin; however, specific chemokine-mediated signaling in irradiated KO skin led to more neutrophil recruitment, thereby aggravating radiation toxicities. Increased skin damage in irradiated KO skin led to hyperproliferation, abnormal differentiation, and cornification of keratinocytes, accompanied by increased upregulation of transcription-factor JunB. Lack of radiation-induced H2A.J expression in keratinocytes is associated with increased senescence induction, modulation of SASP expression, and exacerbated inflammatory skin reactions. Hence, epigenetic H2A.J-mediated gene expression in response to IR regulates keratinocyte immune functions and plays an essential role in balancing the inflammatory response during radiation dermatitis.

Ginsenoside CK inhibits androgenetic alopecia by regulating Wnt/β‐catenin and p53 signaling pathways in AGA mice

AbstractAndrogenetic alopecia (AGA) is one of the most common chronic skin diseases caused by the destruction of androgens in the body. It is caused by the excessive deposition of dihydrotestosterone around the hair follicle, resulting in hair follicle atrophy and hair cell apoptosis. It causes great anxiety and psychological distress to patients and affects sexual function in severe cases. As traditional Chinese herbs, ginsenosides have been proven to possess various pharmacological activities. Ginsenoside CK is one of the main ginsenosides, but its role and molecular mechanism in treating AGA remain unclear. Here, we found that ginsenoside CK intervention significantly reduced back hair loss in AGA mice, improved sexual organ damage and hair follicle cell apoptosis, and promoted hair growth in AGA mice. Ginsenoside CK treatment inhibited p53 expression, reduced the apoptosis of hair follicle cells induced by hormone deposition, activated the Wnt/β‐catenin cell proliferation signaling pathway, increased the level of vascular endothelial growth factor, promoted cell proliferation, and improved the atrophy of hair follicle tissue. Ginsenoside CK treatment also reduced testosterone levels in AGA mice, improved testicular tissue inflammation, and restored normal hormone metabolism in AGA mice. Our results indicated that ginsenoside CK reduced hair follicle cell apoptosis, promoted proliferation and development, and prolonged the hair growth cycle by regulating the Wnt and p53 signaling pathways, indicating the potential value of ginsenoside CK as a natural therapeutic agent for AGA.

Stem Cell Applications in Human Hair Growth: A Literature Review.

Stem cells are being investigated in applications in male pattern baldness and other forms of alopecia of the human scalp. This report explores the literature regarding the various applications of stem cells and their potential for future use in the correction of multifactorial etiologies for male or female pattern baldness. Different contemporary studies revealed that stem cells may be directly injected into the scalp to allow the growth of new hair follicles in males or females for the correction of alopecia.Stem cells may also be used in growth factor stimulation of existing inactive and atrophic follicles to yet again become viable and active follicles. Additional studies indicate that various regulatory mechanisms may be used to reinitiate the existing inactive follicle cells to regrow hair in male pattern baldness. Stem cells injected into the scalp could aid these regulatory mechanisms. In the future, stem cell treatment may serve as a viable option superior to the USFood and Drug Administration (FDA)-approved invasive and noninvasive techniques currently used to combat alopecia.

The features of developing rat autoimmune pathology with mitochondrial dysfunction

The central role of the mitochondria in energy supply and cell death determines highlight these organelles as one of the promising objects for investigating pathogenesis of immune-mediated inflammatory disorders. The aim: to study features of pathogenesis in rat adjuvant-induced autoimmune pathology separately and in combination with mitochondrial disorders. Materials and methods. Wistar rats were divided into groups of negative control (solvent), positive control (single subcutaneous injection of complete Freunds adjuvant (CAF) at dose of 0.1 ml/200 g body weight), experimental (CAF 0.1 ml/200 g body weight and 5 weeks later with cuprizone 0.2% per feed weight). At the end of experiment (7 weeks), animals were tested in the open field model, euthanized, and biomaterial was collected to measure the relative mass coefficients of internal organs, hematological and histological studies. We calculated the mean, standard error of the mean; comparison of hypotheses was carried out by paired Students t-test. Results. In case of impaired immunological tolerance there was detected reduced rat body weight gain during the study period (negative control +74.7 g, positive control +10.3 g) along with modelled mitochondrial dysfunction, a general decrease in weight by 6.7 g was noted. The magnitude of mass coefficients indicate a relative reduction in mass of liver, kidneys, spleen and thymus in experimental animals. The leukocyte counts ( 109/L) are as follows: negative control 8.680.37, positive control 10.981.03 (p 0.05), experimental group 12.280.63 (p 0.001). No significant changes were found in the leukocyte formula and the red cell lineage. During modelled autoimmune pathology, platelet count increased by 22.5% (p 0.05), whereas after cuprizone was administered it decreased by 6.3% (relative to the negative control). Mitochondrial dysfunction caused an abrupt decrease in motor activity in rats: the number of crossed sectors in positive control animals was 55.506.91, experimental group 44.503.60 (inter-group comparison, p 0.001). Positive control: enlarged lymphatic nodules were found in the spleen, germinal center clarification, wall thickening of the pulpal and central arteries; single foci of hemorrhages in the red pulp. Experimental group: atrophy of lymphoid follicles of varying severity (relative to the groups of negative and positive controls), numerous foci of hemorrhages with hemosiderosis in the red pulp. Conclusion. Mitochondrial dysfunction is accompanied by augmented pathogenetic signs of autoimmune pathology, which can serve as one of the keys to understanding the mechanisms of human autoimmunity.

EPCAM and TROP2 share a role in claudin stabilization and development of intestinal and extraintestinal epithelia in mice.

ABSTRACTEpithelial cell adhesion molecule (EPCAM) is a transmembrane glycoprotein expressed on the surface of most epithelial and epithelium-derived tumor cells and reported to regulate stability of epithelial tight junction proteins, claudins. Despite its widespread expression, loss of EPCAM function has so far only been reported to prominently affect intestinal development, resulting in severe early onset enteropathy associated with impaired growth and decreased survival in both humans and mice. In this study, we show that the critical role of EPCAM is not limited to intestinal tissues and that it shares its essential function with its only known homolog, Trophoblast cell surface antigen 2 (TROP2). EPCAM-deficient mice show significant growth retardation and die within 4 weeks after birth. In addition to changes in small and large intestines, loss of EPCAM results in hyperkeratosis in the skin and forestomach, hair follicle atrophy leading to alopecia, nephron hypoplasia in the kidney, proteinuria, and altered production of digestive enzymes by the pancreas. Expression of TROP2 partially, but not completely, overlaps with EPCAM in a number developing epithelia. Although loss of TROP2 had no gross impact on mouse development and survival, TROP2 deficiency generally compounded developmental defects observed in EPCAM-deficient mice, led to an approximately 60% decrease in embryonic viability, and further shortened postnatal lifespan of born pups. Importantly, TROP2 was able to compensate for the loss of EPCAM in stabilizing claudin-7 expression and cell membrane localization in tissues that co-express both proteins. These findings identify overlapping functions of EPCAM and TROP2 as regulators of epithelial development in both intestinal and extraintestinal tissues.

Characterization and pathogenicity of infectious bursal disease virus in Southern China

Infectious bursal disease virus (IBDV) is a widespread pathogen that induces immunosuppression in 3 to 6-wk-old chickens, casuing great threaten to the poultry industry worldwide. Previously, the very virulent IBDV (vvIBDV) was mainly prevalent in China. In recent years, the novel variant IBDV (nvIBDV) occurred in China. In this study, we isolated 30 IBDV strains of IBDV from vaccinated chicken flocks in 8 provinces of southern China. Among these isolates, vvIBDV group (13/30) and nvIBDV group (17/30) were identified according to the genome sequencing and phylogenic analysis. Moreover, HB2021-5 and GD2021-17 have pathologic characteristics with severe bursal lesions, as evidenced by necrosis, depletion of lymphocytes, and follicle atrophy. Our findings provide an important reference for understanding the epidemiological status and the evolution of IBDV.

Lymphadenitis possibly due to human herpesvirus 7 during methotrexate therapy for rheumatoid arthritis

A 75-year-old woman who was treated with methotrexate (MTX) for rheumatoid arthritis was admitted to our hospital because of fever and loss of appetite. Physical examination revealed exanthems in the upper limbs and systemic lymphadenopathy. Her blood test showed elevated levels of serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R). Lymph node biopsy indicated atrophic follicles, interfollicular hyperplasia, and infiltration of macrophages phagocytosing nuclear debris and T-lymphocytes. This suggested lymphadenitis associated with viral infection. Human herpesvirus 7 (HHV-7) DNA was detected in the lymphoid tissue using polymerase chain reaction. The patient was successfully treated with MTX discontinuation and short-term administration of dexamethasone. Her symptoms improved, and LDH and sIL-2R levels were normalized. Human herpesvirus reactivates in patients with immunodeficiency on MTX administration. To the best of our knowledge, this is a valuable case of lymphadenitis considered to have been caused by HHV-7.

Photobiomodulation promotes hair regeneration in injured skin by enhancing migration and exosome secretion of dermal papilla cells.

The application of photobiomodulation (PBM) in regenerative medicine has expanded to the treatment of alopecia caused by various reasons. However, the mechanisms responsible for its effects are poorly understood. Here, we aimed to investigate the effects of PBM on hair regeneration in injured skin and to explore the underlying mechanisms. The scratched epidermis or dermis models were established in C57 mice aged 7-8 weeks. We found that the scratched epidermis had no influence on hair regeneration, but the scratched dermis led to obvious hair follicle atrophy and significantly influenced hair regeneration. The wounds in scratched dermis models were treated with PBM (655 nm, 3J/cm2 [10min]) and the hair regeneration and cell proliferation in hair follicle were evaluated. Compared with control, the hair coverage level was significantly enhanced after PBM treatment. Sox9+ and PCNA+ cells in hair follicle were obviously observed in PBM-treated group, but not in control. In vitro, the effects of PBM on the function of dermal papilla cells (DPCs) were investigated. The results showed that the migration of DPCs was increased significantly by PBM (655 nm, 3J/cm2 [10min]), whereas no effect was found on proliferation. Furthermore, we found that PBM promoted exosome secretion of DPCs, accompanied by the activation of Akt/GSK-3β/β-catenin pathway. AKT inhibitor MK-2206 effectively blocked PBM-induced migration and exosome secretion of DPCs. These findings suggest that the enhanced migration and exosome secretion of DPCs mediated by the Akt/GSK-3β/β-catenin pathway were responsible for the promotion of hair regeneration in injured skin by PBM.

Characterization and pathogenicity of a naturally reassortant and recombinant infectious bursal disease virus in China.

Infectious bursal disease virus (IBDV), an Avibirnavirus, is the pathogen of infectious bursal disease, which is a severely immunosuppressive disease in 3-15-week-old chickens. Different phenotypes of IBDV, including classical, variant, very virulent (vv) and attenuated IBDV, have been reported in many chicken-rearing countries worldwide. Here, we isolated and identified a naturally reassortant and recombinant IBDV (designated GXB02) from 20-day-old chickens with clinicopathological changes of infectious bursal disease (IBD) in Guangxi Province, China. Whole genomic sequencing showed that the strain GXB02 simultaneously has both reassortant and recombinant characteristics with segments A and B being derived from recombinant intermediate vaccine strain and classic strains of IBDV. Segment A of strain GXB02 was incorporated into the skeleton of an intermediate IBDV vaccine strain (W2512), where the breakpoints of two recombinant events located at nucleotide positions 1468 and 1648 were replaced by reassortant vvIBDV (PK2) and vvIBDV (D6948) of segment A, respectively. We used this GXB02 strain to inoculate 21-day-old specific-pathogen-free chickens to evaluate its pathogenicity. Strain GXB02 has clinicopathologic characteristics of IBD with severe bursal lesions, as evidenced by necrosis, depletion of lymphocytes, and follicle atrophy, indicating that reassortment with classical strains in segment B or/and recombination with very virulent strains increased pathogenicity of the strain GXB02 in chickens. These findings provide important insights into the genetic exchange between classic and attenuated strains of IBDV with two recombinant events occurring at the intermediate derivative segment A with vvIBDV strains, thereby increasing the difficulty of prevention and control of IBD due to novel reassortant-recombinant strains.

Liver-spleen axis dysfunction in COVID-19

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an acute infectious disease that spreads mainly through the respiratory route. Besides interstitial pneumonia, a number of other clinical manifestations were noticed in COVID-19 patients. In particular, liver and spleen dysfunctions have been described both as complications of COVID-19 and as potential predisposing factors for severe COVID-19. Liver damage is rather common in COVID-19 patients, and it is most likely multifactorial, caused by the direct insult of SARS-CoV-2 to the liver by the cytokine storm triggered by the virus, by the use of hepatotoxic drugs, and as a consequence of hypoxia. Although generally mild, liver impairment has been found to be associated with a higher rate of intensive care unit admission. A higher mortality rate was reported among chronic liver disease patients. Instead, spleen impairment in patients with COVID-19 has been poorly described. The main anatomical changes are the architectural derangement of the B cell compartment, white pulp atrophy, and reduction or absence of lymphoid follicles, while, from a functional point of view, the IgM memory B cell pool is markedly depleted. The outcome of COVID-19 in asplenic or hyposplenic patients is yet to be defined. In this review, we will summarise the current knowledge regarding the impact of SARS-CoV-2 on the liver and spleen function, as well as the outcome of patients with a pre-existent liver disease or defective spleen function.

FLASH Proton Radiotherapy Spares Normal Epithelial and Mesenchymal Tissues While Preserving Sarcoma Response

In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiotherapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages of PRT to FLASH dose rates (>40 Gy/second), making it important to understand if and how F-PRT spares normal tissues while providing antitumor efficacy that is equivalent to standard-proton radiotherapy (S-PRT). Here we studied PRT damage to skin and mesenchymal tissues of muscle and bone and found that F-PRT of the C57BL/6 murine hind leg produced fewer severe toxicities leading to death or requiring euthanasia than S-PRT of the same dose. RNA-seq analyses of murine skin and bone revealed pathways upregulated by S-PRT yet unaltered by F-PRT, such as apoptosis signaling and keratinocyte differentiation in skin, as well as osteoclast differentiation and chondrocyte development in bone. Corroborating these findings, F-PRT reduced skin injury, stem cell depletion, and inflammation, mitigated late effects including lymphedema, and decreased histopathologically detected myofiber atrophy, bone resorption, hair follicle atrophy, and epidermal hyperplasia. F-PRT was equipotent to S-PRT in control of two murine sarcoma models, including at an orthotopic intramuscular site, thereby establishing its relevance to mesenchymal cancers. Finally, S-PRT produced greater increases in TGFβ1 in murine skin and the skin of canines enrolled in a phase I study of F-PRT versus S-PRT. Collectively, these data provide novel insights into F-PRT-mediated tissue sparing and support its ongoing investigation in applications that would benefit from this sparing of skin and mesenchymal tissues. SIGNIFICANCE: These findings will spur investigation of FLASH radiotherapy in sarcoma and additional cancers where mesenchymal tissues are at risk, including head and neck cancer, breast cancer, and pelvic malignancies.