Modern techniques in addressing facial acne scars: A thorough analysis.

BACKGROUND: Facial acne scars are a prevalent concern, leading to the development of various treatment modalities. OBJECTIVES: This review aims to explore the latest advancements in the treatment of facial acne scars, focusing on both surgical and non-surgical methods. METHODS: The non-surgical treatments reviewed include topical medications (such as retinoids and alpha hydroxy acids) and non-invasive procedures (like microdermabrasion and chemical peels). Surgical options discussed are punch excision, subcision, and fractional laser treatments. RESULTS: Combination therapy, integrating both surgical and non-surgical approaches, is frequently utilized to achieve optimal results in scar improvement. CONCLUSION: Recent advancements in the treatment of facial acne scars provide promising options for individuals seeking improvement. However, these treatments have associated risks and potential adverse effects, highlighting the importance of consulting a dermatologist before beginning any treatment regimen.

Effectiveness and safety of awake prone positioning in COVID-19-related acute hypoxaemic respiratory failure: an overview of systematic reviews.

OBJECTIVE: To evaluate and summarize systematic reviews of the effects and safety of awake prone positioning for COVID-19-related acute hypoxaemic respiratory failure. METHODS: A comprehensive search was conducted on PubMed, Embase, the Cochrane Library, Web of Science, CNKI, CSPD, CCD and CBM from their inception to March 28, 2023. Systematic reviews (SRs) of awake prone positioning (APP) for COVID-19-related acute hypoxaemic respiratory failure in adults were included. Two reviewers screened the eligible articles, and four reviewers in pairs extracted data and assessed the methodological quality/certainty of the evidence of all included SRs by AMSTAR 2 and GRADE tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a narrative description. RESULTS: A total of 11 SRs were included. The methodological quality of SRs included 1 "High", 4 "Moderate", 2 "Low" and 4 "Critically low" by AMSTAR 2. With the GRADE system, no high-quality evidence was found, and only 14 outcomes provided moderate-quality evidence. Data synthesis of the included SR outcomes showed that APP reduced the risk of requiring intubation (11 SRs) and improving oxygenation (3 SRs), whereas reduced significant mortality was not found in RCT-based SRs. No significant difference was observed in the incidence of adverse events between groups (8 SRs). The corrected covered area index was 27%, which shows very high overlap among studies. CONCLUSION: The available SRs suggest that APP has benefits in terms of reducing intubation rates and improving oxygenation for COVID-19-related acute hypoxemic respiratory failure, without an increased risk of adverse events. The conclusion should be treated with caution because of the generally low quality of methodology and evidence. TRIAL REGISTRATION: The protocol for this review was registered with PROSPERO: CRD42023400986. Registered 15 April 2023.

Polysaccharide extracted from the Sargassum fusiforme induces cell cycle arrest and apoptosis of B16F10 melanoma cells through the PI3K/AKT pathway.

BACKGROUND: SARGASSUM FUSIFORME: (S. fusiforme) is a brown alga that has been utilized as a medicine for a long time. Polysaccharides extracted from S. fusiforme demonstrate antitumor activities. METHODS: The impact of S. fusiforme polysaccharides (SFPS 191,212) on the proliferation, apoptosis, and cell cycle kinetics of B16F10 murine melanoma cells were thoroughly investigated in this work. The anticancer activities of the SFPS 191,212 compounds were assayed in the B16F10 cells at both transcriptional and translational levels. RESULTS: The compound exhibited concentration-dependent effects. Moreover, SPFS 191,212 increased the numbers of apoptotic cells and arrested the cell cycle in the S phase of the quantitative real-time PCR. From western blotting, it was verified that the SFPS 191,212 treatment improved the expression of Bax, Caspase-9, and Caspase-3 genes and proteins, while it reduced phosphatidylinositol 3 kinase and Bcl-2 genes and proteins, suggesting the involvement of mitochondria. CONCLUSION: Overall, SFPS 191,212 can be further explored as a potential functional food or adjuvant agent for the prevention or treatment of melanoma.

Mechanisms underlying pathological scarring by fibroblasts during wound healing.

Pathological scarring is an abnormal outcome of wound healing, which often manifests as excessive proliferation and transdifferentiation of fibroblasts (FBs), and excessive deposition of the extracellular matrix. FBs are the most important effector cells involved in wound healing and scar formation. The factors that promote pathological scar formation often act on the proliferation and function of FB. In this study, we describe the factors that lead to abnormal FB formation in pathological scarring in terms of the microenvironment, signalling pathways, epigenetics, and autophagy. These findings suggest that understanding the causes of abnormal FB formation may aid in the development of precise and effective preventive and treatment strategies for pathological scarring that are associated with improved quality of life of patients.

Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway.

BACKGROUND: Glioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences. Understanding the tumor-nontumor cell interaction in TME is critical for developing new therapy. Glioblastomas are known to recruit normal cells in their environs to sustain growth and encroachment into other regions. Neural progenitor cells (NPCs) have been noted to migrate towards the site of glioblastomas, however, the detailed mechanisms underlying glioblastoma-mediated NPCs' alteration remain unkown. METHODS: We collected EVs in the culture medium of three classic glioblastoma cell lines, U87 and A172 (male cell lines), and LN229 (female cell line). U87, A172, and LN229 were co-cultured with their corresponding EVs, respectively. Mouse NPCs (mNPCs) were co-cultured with glioblastoma-derived EVs. The proliferation and migration of tumor cells and mNPCs after EVs treatment were examined. Proteomic analysis and western blotting were utilized to identify the underlying mechanisms of glioblastoma-derived EVs-induced alterations in mNPCs. RESULTS: We first show that glioblastoma cell lines U87-, A172-, and LN229-derived EVs were essential for glioblastoma cell prolifeartion and migration. We then demonstrated that glioblastoma-derived EVs dramatically promoted NPC proliferation and migration. Mechanistic studies identify that glioblastoma-derived EVs achieve their functions via activating PI3K-Akt-mTOR pathway in mNPCs. Inhibiting PI3K-Akt pathway reversed the elevated prolfieration and migration of glioblastoma-derived EVs-treated mNPCs. CONCLUSION: Our findings demonstrate that EVs play a key role in intercellular communication in tumor microenvironment. Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy. Video Abstract.

Induced neural progenitor cells abundantly secrete extracellular vesicles and promote the proliferation of neural progenitors via extracellular signal-regulated kinase pathways.

Neural stem/progenitor cells (NPCs) are known to have potent therapeutic effects in neurological disorders through the secretion of extracellular vesicles (EVs). Despite the therapeutic potentials, the numbers of NPCs are limited in the brain, curbing the further use of EVs in the disease treatment. To overcome the limitation of NPC numbers, we used a three transcription factor (Brn2, Sox2, and Foxg1) somatic reprogramming approach to generate induced NPCs (iNPCs) from mouse fibroblasts and astrocytes. The resulting iNPCs released significantly higher numbers of EVs compared with wild-type NPCs (WT-NPCs). Furthermore, iNPCs-derived EVs (iNPC-EVs) promoted NPC function by increasing the proliferative potentials of WT-NPCs. Characterizations of EV contents through proteomics analysis revealed that iNPC-EVs contained higher levels of growth factor-associated proteins that were predicted to activate the down-stream extracellular signal-regulated kinase (ERK) pathways. As expected, the proliferative effects of iNPC-derived EVs on WT-NPCs can be blocked by an ERK pathway inhibitor. Our data suggest potent therapeutic effects of iNPC-derived EVs through the promotion of NPC proliferation, release of growth factors, and activation of ERK pathways. These studies will help develop highly efficient cell-free therapeutic strategies for the treatment of neurological diseases.

Exosomes released from neural progenitor cells and induced neural progenitor cells regulate neurogenesis through miR-21a.

Neural stem/progenitor cells (NPCs) are known to have potent therapeutic effects in neurological disorders through secreting exosomes. The limited numbers of NPCs in adult brain and the decline of NPC pool in many neurological disorders restrain the further use of exosomes in treating these diseases. The direct conversion of somatic cells into induced NPCs (iNPCs) provides abundant NPC-like cells to study the therapeutic effects of NPCs-originated exosomes (EXOs). Our recent study demonstrated that iNPCs-derived exosomes (iEXOs) exhibit distinct potential in facilitating the proliferation of NPCs, compared to EXOs, indicating the importance to investigate the effects of EXOs and iEXOs on the differentiation of NPCs, which remains unknown. Here, our results suggest that EXOs, but not iEXOs, promoted neuronal differentiation and neither of them had effect on glial generation. Microarray analysis revealed different miRNA signatures in EXOs and iEXOs, in which miR-21a was highly enriched in EXOs. Perturbation of function assay demonstrated the key roles of miR-21a in the generation of neurons and mediating the neurogenic potential of exosomes. Our data suggest that EXOs and iEXOs may achieve their therapeutic effects in promoting neurogenesis through transferring key miRNAs, which sheds light on the development of highly efficient cell-free therapeutic strategies for treating neurological diseases.

Transformer guided self-adaptive network for multi-scale skin lesion image segmentation.

BACKGROUND: In recent years, skin lesion has become a major public health concern, and the diagnosis and management of skin lesions depend heavily on the correct segmentation of the lesions. Traditional convolutional neural networks (CNNs) have demonstrated promising results in skin lesion segmentation, but they are limited in their ability to capture distant connections and intricate features. In addition, current medical image segmentation algorithms rarely consider the distribution of different categories in different regions of the image and do not consider the spatial relationship between pixels. OBJECTIVES: This study proposes a self-adaptive position-aware skin lesion segmentation model SapFormer to capture global context and fine-grained detail, better capture spatial relationships, and adapt to different positional characteristics. The SapFormer is a multi-scale dynamic position-aware structure designed to provide a more flexible representation of the relationships between skin lesion characteristics and lesion distribution. Additionally, it increases skin lesion segmentation accuracy and decreases incorrect segmentation of non-lesion areas. INNOVATIONS: SapFormer designs multiple hybrid transformers for multi-scale feature encoding of skin images and multi-scale positional feature sensing of the encoded features using a transformer decoder to obtain fine-grained features of the lesion area and optimize the regional feature distribution. The self-adaptive feature framework, built upon the transformer decoder module, dynamically and automatically generates parameterizations with learnable properties at different positions. These parameterizations are derived from the multi-scale encoding characteristics of the input image. Simultaneously, this paper utilizes the cross-attention network to optimize the features of the current region according to the features of other regions, aiming to increase skin lesion segmentation accuracy. MAIN RESULTS: The ISIC-2016, ISIC-2017, and ISIC-2018 datasets for skin lesions are used as the basis for the experiment. On these datasets, the proposed model has accuracy values of 97.9 %, 94.3 %, and 95.7 %, respectively. The proposed model's IOU values are, in order, 93.2 %, 86.4 %, and 89.4 %. The proposed model's DSC values are 96.4 %, 92.6 %, and 94.3 %, respectively. All three metrics surpass the performance of the majority of state-of-the-art (SOTA) models. SapFormer's metrics on these datasets demonstrate that it can precisely segment skin lesions. Notably, our approach exhibits remarkable noise resistance in non-lesion areas, while simultaneously conducting finer-grained regional feature extraction on the skin lesion image. CONCLUSIONS: In conclusion, the integration of a transformer-guided position-aware network into semantic skin lesion segmentation results in a notable performance boost. The ability of our proposed network to capture spatial relationships and fine-grained details proves beneficial for effective skin lesion segmentation. By enhancing lesion localization, feature extraction, quantitative analysis, and classification accuracy, the proposed segmentation model improves the diagnostic efficiency of skin lesion analysis on dermoscopic images. It assists dermatologists in making more accurate and efficient diagnoses, ultimately leading to better patient care and outcomes. This research paves the way for advances in diagnosing and treating skin lesions, promoting better understanding and decision-making in the clinical setting.

Exogenous drug-induced mouse models of atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory skin disease characterized by intense pruritus. AD is harmful to both children and adults, but its pathogenic mechanism has yet to be fully elucidated. The development of mouse models for AD has greatly contributed to its study and treatment. Among these models, the exogenous drug-induced mouse model has shown promising results and significant advantages. Until now, a large amount of AD-related research has utilized exogenous drug-induced mouse models, leading to notable advancements in research. This indicates the crucial significance of applying such models in AD research. These models exhibit diverse characteristics and are highly complex. They involve the use of various strains of mice, diverse types of inducers, and different modeling effects. However, there is currently a lack of comprehensive comparative studies on exogenous drug-induced AD mouse models, which hinders researchers' ability to choose among these models. This paper provides a comprehensive review of the features and mechanisms associated with various exogenous drug-induced mouse models, including the important role of each cytokine in AD development. It aims to assist researchers in quickly understanding models and selecting the most suitable one for further investigation.

[Acupuncture and moxibustion in treatment of chronic obstructive pulmonary disease at stable stage: a network Meta-analysis].

The efficacy on chronic obstructive pulmonary disease (COPD) at stable stage treated with different methods of acupuncture and moxibustion was evaluated using network Meta-analysis method. The articles of the randomized controlled trial (RCT) on stable COPD treated with acupuncture and moxibustion were searched electronically in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science and Cochrane library. The search was conducted from the inception of the databases to March 20th, 2022. Data analysis was performed using R4.1.1, Stata16.0 and RevMan5.3 softwares. A total of 48 RCTs were included, involving 15 kinds of acupuncture and moxibustion interventions and a sample size of 3 900 cases. The results of network Meta-analysis showed that: ① For the forced expiratory volume in one second predicted (FEV1%), both the governor vessel moxibustion combined with conventional treatment (G+C therapy) and the yang-supplementing moxibustion combined with conventional treatment (Y+C therapy) obtained the better effect than that of the conventional treatment (P<0.05), and the G+C therapy was more effective compared with the thread-embedding therapy combined with conventional treatment (E+C therapy) and warm needling (P<0.05). ② Concerning to COPD assessment test (CAT) score, the results indicated that the Y+C therapy, and the mild moxibustion combined with conventional treatment (M+C therapy) were more effective when compared with the conventional treatment (P<0.05), and the effect of the Y+C therapy was better than that of the E+C therapy (P<0.05). ③ Regarding six-minute walking distance (6MWD), the effect of acupuncture combined with conventional treatment (A+C therapy) was better than that of either the E+C therapy or the conventional treatment (P<0.05). The effect of the G+C therapy was optimal for improving FEV1%, the Y+C therapy obtained the best effect for improving CAT score, and A+C therapy was the most effective for improving 6MWD. Due to the limitation of the quality and quantity of included studies, this conclusion needs to be further verified through high-quality RCT.

Fecal microbiota transplantation affects the recovery of AD-skin lesions and enhances gut microbiota homeostasis.

BACKGROUND: Accumulating evidence has shown that gut microbiota plays a key role in the progression of atopic dermatitis (AD). Fecal microbiota transplantation (FMT), as an effective method to restore gut microbiota homeostasis, has been successfully applied for treating many inflammatory diseases. However, the therapeutic effect of FMT on AD remains unclear. The following study examined the effect and mechanism of FMT on AD-skin lesions in an AD mouse model. METHODS: In this study, we exposed the shaved back skin of BALB/c mice to calcipotriol (MC903) to induce AD model. Mice were then treated with FMT, which was performed with gut microbiota from healthy mice. The gut microbiota of treated mice was tracked by 16S rRNA gene sequencing. Mice skin tissues were examined by histopathology and inflammatory cytokines change in serum by ELISA. RESULTS: FMT had a faster trend on the reversion of the increases in skin epidermal layer thicknesses and suppressed some of the representative inflammatory cytokines. The gut microbial community in the natural recovery process varied significantly in the FMT group at day 7 (ANOSIM P = 0.0229, r = 0.2593). Notably, FMT had a long-lasting and beneficial impact on the gut microbial compositions of AD mice by increasing the ratio of Firmicutes to Bacteroidetes and the amount of butyric-producing bacteria (BPB), including Erysipelotrichaceae, Lactobacillaceae, and Eubacteriacea. Furthermore, the relative abundances of gut microbiota-mediated functional pathways involved in the cell growth and death, amino acid, energy, lipid, and carbohydrate metabolisms, and immune system increased after FMT treatment. CONCLUSION: FMT modulated the gut microbiota homeostasis and affected the recovery from AD-related inflammations, suggesting that it could be used as a treatment strategy for AD patients in the clinic.

An improved transformer network for skin cancer classification.

BACKGROUND: Use of artificial intelligence to identify dermoscopic images has brought major breakthroughs in recent years to the early diagnosis and early treatment of skin cancer, the incidence of which is increasing year by year worldwide and poses a great threat to human health. Achievements have been made in the research of skin cancer image classification by using the deep backbone of the convolutional neural network (CNN). This approach, however, only extracts the features of small objects in the image, and cannot locate the important parts. OBJECTIVES: As a result, researchers of the paper turn to vision transformers (VIT) which has demonstrated powerful performance in traditional classification tasks. The self-attention is to improve the value of important features and suppress the features that cause noise. Specifically, an improved transformer network named SkinTrans is proposed. INNOVATIONS: To verify its efficiency, a three step procedure is followed. Firstly, a VIT network is established to verify the effectiveness of SkinTrans in skin cancer classification. Then multi-scale and overlapping sliding windows are used to serialize the image and multi-scale patch embedding is carried out which pay more attention to multi-scale features. Finally, contrastive learning is used which makes the similar data of skin cancer encode similarly so that the encoding results of different data are as different as possible. MAIN RESULTS: The experiment is carried out based on two datasets, namely (1) HAM10000: a large dataset of multi-source dermatoscopic images of common skin cancers; (2)A clinical dataset of skin cancer collected by dermoscopy. The model proposed has achieved 94.3% accuracy on HAM10000 and 94.1% accuracy on our datasets, which verifies the efficiency of SkinTrans. CONCLUSIONS: The transformer network has not only achieved good results in natural language but also achieved ideal results in the field of vision, which also lays a good foundation for skin cancer classification based on multimodal data. This paper is convinced that it will be of interest to dermatologists, clinical researchers, computer scientists and researchers in other related fields, and provide greater convenience for patients.

Induced neural progenitor cell-derived extracellular vesicles promote neural progenitor cell survival via extracellular signal-regulated kinase pathway.

Proposed model for the anti-apoptotic effects of induced neural stem/progenitor cell (iNPC)-derived extracellular vesicles (EVs). iNPC release EVs that are abundantly loaded with growth factor-related proteins. These growth factor-enriched EVs enhance the phosphorylation of extracellular signal-regulated kinase (ERK), but not AKt. The EV-induced activation of ERK pathway then inhibit the apoptosis of NPCs in various pathological conditions including oxidative stress and starvation.

Neural Stem Cell-Derived Exosomes Regulate Neural Stem Cell Differentiation Through miR-9-Hes1 Axis.

Exosomes, a key element of the central nervous system microenvironment, mediate intercellular communication via horizontally transferring bioactive molecules. Emerging evidence has implicated exosomes in the regulation of neurogenesis. Recently, we compared the neurogenic potential of exosomes released from primary mouse embryonic neural stem cells (NSCs) and astrocyte-reprogrammed NSCs, and observed diverse neurogenic potential of those two exosome populations in vitro. However, the roles of NSC-derived exosomes on NSC differentiation and the underlying mechanisms remain largely unknown. In this study, we firstly demonstrated that NSC-derived exosomes facilitate the differentiation of NSCs and the maturation of both neuronal and glial cells in defined conditions. We then identified miR-9, a pro-neural miRNA, as the most abundantly expressed miRNA in NSC-derived exosomes. The silencing of miR-9 in exosomes abrogates the positive effects of NSC-derived exosomes on the differentiation of NSCs. We further identified Hes1 as miR-9 downstream target, as the transfection of Hes1 siRNA restored the differentiation promoting potential of NSC-derived exosomes after knocking down exosomal miR-9. Thus, our data indicate that NSC-derived exosomes facilitate the differentiation of NSCs via transferring miR-9, which sheds light on the development of cell-free therapeutic strategies for treating neurodegeneration.

Reprogrammed astrocytes display higher neurogenic competence, migration ability and cell death resistance than reprogrammed fibroblasts.

The direct reprogramming of somatic cells into induced neural progenitor cells (iNPCs) has been envisioned as a promising approach to overcome ethical and clinical issues of pluripotent stem cell transplantation. We previously reported that astrocyte-derived induced pluripotent stem cells (iPSCs) have more tendencies for neuronal differentiation than fibroblast-derived iPSCs. However, the differences of neurogenic potential between astrocyte-derived iNPCs (AiNPCs) and iNPCs from non-neural origins, such as fibroblast-derived iNPCs (FiNPCs), and the underlying mechanisms remain unclear. Our results suggested that AiNPCs exhibited higher differentiation efficiency, mobility and survival capacities, compared to FiNPCs. The whole transcriptome analysis revealed higher activities of TGFß signaling in AiNPCs, versus FiNPCs, following a similar trend between astrocytes and fibroblasts. The higher neurogenic competence, migration ability, and cell death resistance of AiNPCs could be abrogated using TGFß signaling inhibitor LY2157299. Hence, our study demonstrates the difference between iNPCs generated from neural and non-neural cells, together with the underlying mechanisms, which, provides valuable information for donor cell selection in the reprogramming approach.

Direct conversion of mouse astrocytes into neural progenitor cells and specific lineages of neurons.

BACKGROUND: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation. METHODS: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2. The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a. RESULTS: Astrocyte-derived induced NPCs (AiNPCs) share high similarities, including the expression of NPC-specific genes, DNA methylation patterns, the ability to proliferate and differentiate, with the wild type NPCs. The AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal subtypes. Interestingly, additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation, respectively. CONCLUSIONS: Our studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs. Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases.