Empathic pain: Exploring the multidimensional impacts of biological and social aspects in pain.

Empathic pain refers to an individual's perception, judgment, and emotional response to others' pain. This complex social cognitive ability is crucial for healthy interactions in human society. In recent years, with the development of multidisciplinary research in neuroscience, psychology and sociology, empathic pain has become a focal point of widespread attention in these fields. However, the neural mechanism underlying empathic pain remain a controversial and unresolved area. This review aims to comprehensively summarize the history, influencing factors, neural mechanisms and pharmacological interventions of empathic pain. We hope to provide a comprehensive scientific perspective on how humans perceive and respond to others' pain experiences and to provide guidance for future research directions and clinical applications. This article is part of the Special Issue on "Empathic Pain".

IL-17A and TNF-α-induced Dectin-1 expression may promote keratinocyte proliferation in psoriatic lesions.

Psoriasis is a common skin disease with a high recurrence rate. Aberrant keratinocyte proliferation is a significant pathogenic characteristic of psoriatic lesions, and studies have revealed that the development of psoriasis is significantly influenced by pro-inflammatory cytokines, such as IL-17A and TNF-α. Biologics targeting these cytokines have been widely used in psoriasis treatment and achieve remarkable effects, however, the underlying mechanism of how IL-17A and TNF-α specifically regulate keratinocyte proliferation has not been fully elucidated. Dectin-1 is an essential membrane protein that is directly related to the immune microenvironment and the proliferation of multiple cell types. To elucidate how IL-17A and TNF-α may promote keratinocyte proliferation in psoriatic lesions and whether Dectin-1 is involved. The expression of Dectin-1 in keratinocytes from psoriatic lesions was detected by real-time PCR, western blot and immunofluorescence. Correlation analysis and cytological experiments were then performed to determine the relationship between Dectin-1 and IL-17A/TNF-α in psoriatic lesions. Finally, we investigated the signalling pathway through which Dectin-1 may promote keratinocyte proliferation. Dectin-1 was significantly increased in keratinocytes from psoriatic lesions. Moreover, IL-17A and TNF-α effectively induced the expression of Dectin-1 in HaCaT cells, which was shown to activate the Syk/NF-κB signalling pathway and promote the proliferation of keratinocytes. IL-17A and TNF-α may promote the proliferation of keratinocytes in psoriatic lesions through induction of Dectin-1, indicating that Dectin-1 could be a potential therapeutic target for the treatment of psoriasis.

Post intensive care syndrome: A review of clinical symptoms, evaluation, intervention.

Post intensive care syndrome (PICS) is a typical complication of critically ill patients during or after their stay in intensive care unit (ICU), characterized by a high incidence and impairment rate. It significantly impacts the quality of life of patients and their families, as well as consumes a substantial amount of medical resources. Therefore, early intervention and assessment of PICS is crucial. This paper aims to provide clinical professionals with a reference base by focusing on the clinical symptoms, diagnostic assessment, and preventative measures of PICS.

A tungsten-based metamaterial emitter for solar thermophotovoltaic systems.

Solar thermophotovoltaic systems are capable of showing efficient photoelectric conversion and are expected to surpass the Shockley-Queisser limit, owing to the spectrum-selective functionality of metamaterial selective emitters. Generally, metamaterial emitters are manufactured from multifarious materials, which also makes their manufacturing process complicated. Here, we propose a tungsten-only emitter composed of two rectangular bars with different widths and heights arranged in a cruciform structure, featuring a rectangular cavity at the top. Results from the simulations reveal that the emissivity of the metamaterial emitter exceeds 90% at the wavelength of 950-1590 nm and drops below 20% for wavelengths exceeding 2025 nm, which can effectively match GaSb photovoltaic cells. The outstanding emission performance is attributed to the coupling effect of surface plasmon resonance, cavity resonance and guided mode resonance, as evidenced by the analysis of electric and magnetic fields. We also explored the radiation spectrum in the 500-2500 K temperature range and found that it performed best at 1400 K. It is concluded that the emission performance is slightly affected by structural parameters and angles. This study presents a meaningful exploration of efficient solar utilization.

The expression and significance of PD-L1 in condyloma acuminatum.

BACKGROUND: It has been reported that programmed death-ligand 1 (PD-L1) is highly expressed in cells during viral infection, which helps the virus escape host immunity. However, the relationship between human papillomavirus (HPV) and PD-L1 in condyloma acuminatum and whether they participate in immunosuppression have not been reported. In this paper, we aimed to explore the expression and significance of PD-L1 in condyloma acuminatum. METHODS: The expression of PD-L1 in the wart of condyloma acuminatum patients and the foreskin of healthy individuals was evaluated. Lentivirus transfection was used to introduce the HPV11-E7 gene into HaCaT cells to investigate whether HPV infection could affect the expression of PD-L1. The successfully constructed HPV11-E7 HaCaT cells were cocultured with Jurkat cells, and Jurkat cell apoptosis and proliferation as well as the Jurkat cell cycle were evaluated by flow cytometry and cell counting kit-8 (CCK-8) assays. RESULTS: PD-L1 was highly expressed in keratinocytes of genital warts. Through the construction of a cell model, we found that HPV11-E7 could upregulate the expression of PD-L1 in HaCaT cells. Furthermore, HPV11-E7 HaCaT cells can promote the apoptosis of Jurkat cells, inhibit the proliferation of Jurkat cells and mediate the cell cycle arrest of Jurkat cells through the PD-1/PD-L1 signalling pathway. CONCLUSIONS: HPV infection may upregulate PD-L1 expression in the keratinocytes of genital warts and participate in the inhibition of local T-cell function.

WTAP-mediated m6A modification of IFNE is required for antiviral defense in condyloma acuminata.

BACKGROUND: IFN-ε is essential in combating viral infections, particularly in epithelial cells and protected mucosal tissues. Its protective effects have been demonstrated against HSV2, Zika virus, HIV and SARS-COV2. However, the specific expression and role of IFN-ε in skin keratinocytes and HPV infection are still not fully understood and require further investigation. OBJECTIVE: In this study, we aimed to investigate the functions and expression mechanism of IFN-ε in keratinocytes during HPV infection and the progression of condyloma acuminata. METHODS: Keratinocytes isolated from biopsied CA warts and normal skins samples were analyzed by MeRIP-seq analysis. IFN-ε and WTAP in CA warts and normal skins were analyzed by immunostaining and qPCR. RESULTS: In this study, we identified IFN-ɛ was markedly upregulated in CA warts and HPV-infected keratinocytes. IFN-ɛ expression also showed negatively correlation with the size of CA warts (R=-0.4646, P = 0.009). IFN-ɛ suppressed the susceptibility of HPV infection directly. m6A analysis reveals WTAP is a key m6A writer promoting the m6A modification of IFNE mRNA. CONCLUSION: Our research suggests that IFN-ɛ is an important Type I IFN cytokine involved in the development of genital warts. Furthermore, we found that HPV infection affects the m6A modifications of IFNE through a mechanism dependent on WTAP. This study provides insights into the innate immune response of the host to HPV infection and may contribute to the development of future strategies for regulating innate immunity to treat genital warts.

The role of hormones in the pathogenesis and treatment mechanisms of delirium in ICU: The past, the present, and the future.

Delirium is an acute brain dysfunction. As one of the common psychiatric disorders in ICU, it can seriously affect the prognosis of patients. Hormones are important messenger substances found in the human body that help to regulate and maintain the function and metabolism of various tissues and organs. They are also one of the most commonly used drugs in clinical practice. Recent evidences suggest that aberrant swings in cortisol and non-cortisol hormones might induce severe cognitive impairment, eventually leading to delirium. However, the role of hormones in the pathogenesis of delirium still remains controversial. This article reviews the recent research on risk factors of delirium and the association between several types of hormones and cognitive dysfunction. These mechanisms are expected to offer novel ideas and clinical relevance for the treatment and prevention of delirium.

Chemerin Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production.

OBJECTIVE: Psoriasis is often combined with metabolic abnormalities, such as obesity and diabetes. The upregulation of chemerin, which is an essential protein produced primarily from white fat, is strongly correlated to the development of psoriasis. However, there is no clarification on its exact function and mechanism in disease pathogenesis. The present study aims to determine its function and mechanism in disease pathogenesis. METHODS: The present study used a psoriasislike inflammatory cell model and imiquimod (IMQ)-induced mouse model to confirm whether chemerin is upregulated in psoriasis patients. RESULTS: Chemerin enhanced the keratinocyte proliferation, inflammatory cytokine secretion, and activation of the MAPK signaling pathway. Crucially, the intraperitoneal injection of neutralizing anti-chemerin antibody (ChAb) diminished the epidermal proliferation and inflammation in the IMQ-induced mouse model. CONCLUSION: The present results indicate that chemerin promotes keratinocyte proliferation, and enhances the production of inflammatory cytokines, thereby aggravating the psoriasis. Thus, chemerin can be a prospective target for the treatment of psoriasis.

Downregulation of Sonic hedgehog signaling induces G2-arrest in genital warts.

BACKGROUND: Human papillomavirus (HPV) infected keratinocyte dysfunction results in the formation of genital warts, and the specific role of Sonic hedgehog (SHh) signaling in genital warts remains elusive. Thus, this study aimed to identify the correlation between wart formation and SHh signaling. MATERIALS AND METHODS: In this study, nine male patients with genital warts were recruited, and the expression of SHh and its downstream signal molecules Patched-1 and GLI family zinc finger 1 (Ptch1 and Gli1) was detected. Moreover, G2-phase cells in the collected genital warts samples were assessed with normal foreskin samples as a comparison. HPV6/11 were detected via in situ hybridization (ISH), and SHh expression of the corresponding paraffin sections was determined via immunohistochemical staining (IHC). In addition, an in vitro down-regulated SHh model was constructed by siRNA transfection of the HaCaT cell line, and the cell cycle was detected at 36 h by flow cytometry with propidium iodide staining. RESULTS: SHh, Ptch1, and Gli1 in warts were significantly downregulated in the condyloma acuminatum (CA) group compared to the normal foreskin group. G2-phase cells in the middle section of the spinous layer of CA wart tissues were significantly increased. Moreover, the expression of HPV-DNA was amplified and negatively correlated with SHh activity in CA wart tissues. Lastly, the downregulation of SHh-induced G2 arrest in vitro. CONCLUSIONS: The downregulation of the SHh signaling promotes HPV replication and the formation of warts by inducing G2/M arrest in the keratinocytes of CA.

Trace element zinc and skin disorders.

Zinc is a necessary trace element and an important constituent of proteins and other biological molecules. It has many biological functions, including antioxidant, skin and mucous membrane integrity maintenance, and the promotion of various enzymatic and transcriptional responses. The skin contains the third most zinc in the organism. Zinc deficiency can lead to a range of skin diseases. Except for acrodermatitis enteropathic, a rare genetic zinc deficiency, it has also been reported in other diseases. In recent years, zinc supplementation has been widely used for various skin conditions, including infectious diseases (viral warts, genital herpes, cutaneous leishmaniasis, leprosy), inflammatory diseases (hidradenitis suppurativa, acne vulgaris, rosacea, eczematous dermatitis, seborrheic dermatitis, psoriasis, Behcet's disease, oral lichen planus), pigmentary diseases (vitiligo, melasma), tumor-associated diseases (basal cell carcinoma), endocrine and metabolic diseases (necrolytic migratory erythema, necrolytic acral erythema), hair diseases (alopecia), and so on. We reviewed the literature on zinc application in dermatology to provide references for better use.

Nuclear factor I/B mediates epithelial-mesenchymal transition in human melanoma cells through ZEB1.

The relationship between nuclear factor I/B (NFIB) and cancer attracts growing research interest. NFIB has diverse and specific roles in tumor progression and invasion. However, the potential effects and functions of this transcription factor in melanoma remain unclear. The present study sought to determine the distinguishing properties of NFIB in melanoma cells. Immunohistochemical examination of the tissues of 15 patients with melanoma indicated that the expression of NFIB was high in melanoma specimens, compared with the benign nevus and normal skin specimens. In addition, the relationship between high NFIB expression and low overall survival rate was assessed. Functional studies demonstrated that NFIB enhanced the malignancy of melanoma, including proliferation, migration and invasion. In addition, NFIB silencing in A375 and A875 cell lines inhibited the process of epithelial-mesenchymal transition (EMT), upregulated E-cadherin and zona occludens-1, but suppressed N-cadherin and vimentin expression. These findings may suggest a new function of NFIB in promoting the migration and invasion of melanoma cells. Therefore, the present study further evaluated the association between NFIB and zinc finger protein E-box binding homeobox-1 (ZEB1) in melanoma. Mechanistic experiments revealed that NFIB exerted its roles during EMT by regulating ZEB1. Overall, the present data indicates that NFIB promotes the malignancy of melanoma, particularly EMT, by modulating the ZEB1 axis, such as ZEB2, ATM and CHK1, which may represent a potential molecular therapeutic target in melanoma.

Enhanced Glycogen Metabolism Supports the Survival and Proliferation of HPV-Infected Keratinocytes in Condylomata Acuminata.

Condylomata acuminata (CA) is caused by human papillomavirus (HPV) infections of keratinocytes and is a common sexually transmitted disease. The main clinical feature and risk of CA is the high recurrence of genital warts formed by infected keratinocytes. Metabolic reprogramming of most types of mammalian cells including keratinocytes can provide energy and intermediates essential for their survival. Here, we report that HPV infection develops a hypoxic microenvironment in CA warts by inducing the accumulation of glycogen and increased glycogen metabolism in the infected keratinocytes in a hypoxia-inducible factor 1α (HIF-1α) -dependent pathway. Our in vitro studies show that the increased glycogen metabolism is essential for the survival and proliferation of keratinocytes. Regarding its mechanism of action, glycogenolysis generates glucose-1-phosphate that fluxes into the pentose phosphate pathway and, then, generates abundant nicotinamide adenine dinucleotide phosphate, thereby ensuring high levels of glutathione in keratinocytes under hypoxia. The abrogation of glycogen synthesis and glycogenolysis decreases the ratio of glutathione and glutathione disulfide and increases the level of ROS, further resulting in the impairment of keratinocyte survival. Collectively, our work offers an insight into the metabolic reprogramming in the development of CA and implies that the intervention of glycogen metabolism would be a promising therapeutic target for CA.

Melanoma migration is promoted by prion protein via Akt-hsp27 signaling axis.

Patients with metastatic melanoma have a poorer prognosis. Prion protein (PrP) in melanoma is known to play an important role in cancer cell migration and invasion by interacting with filamin A (FLNa), a cytolinker protein. To investigate if PrP may contribute to cancer cell mobility independent of its binding to FLNa, we knocked out PRNP in M2 melanoma cell, which lacked FLNa expression. We found that deletion of PRNP in M2 significantly reduced its motility. When PRNP was deleted, the level of Akt was decreased. As a consequence, phosphorylation of small heat shock protein (hsp27) was also reduced, which resulted in polymerization of F-actin rendering the cells less migratory. Accordingly, when PrP was re-expressed in PRNP null M2 cells, the mobility of the recurred cells was rescued, so were the expression levels of Akt and phosphorylated hsp27, resulting in a decrease in the polymerization of F-actin. These results revealed that PrP can play a FLNa independent role in cytoskeletal organization and tumor cell migration by modulating Akt-hsp27-F-actin axis.

NAV2 facilitates invasion of cutaneous melanoma cells by targeting SNAI2 through the GSK-3ß/ß-catenin pathway.

Previous studies have identified neuron navigator 2(NAV2) as an oncogene in several human tumors. However, the NAV2 gene expression changes and its role in the pathogenesis of cutaneous melanoma have not been clearly illustrated. Further investigations of NAV2 in cutaneous melanoma may provide new mechanistic insight and treatment strategy for this disease. Through immunohistochemistry assay and bioinformatics analysis, we found that melanoma tissues showed an upregulated expression of NAV2 which correlated with poor prognosis of cutaneous melanoma. To investigate the effect of NAV2 on the proliferation and invasion of melanoma, shNAV2 and NAV2-cDNA were transfected into melanoma cell lines. NAV2 overexpression significantly promoted melanoma cell proliferation, migration and invasion, while NAV2 silencing effectively inhibited this process. The potential underlying mechanisms were investigated using bioinformatics analysis, qRT-PCR, and western blot. Results showed that NAV2-mediated invasion of melanoma cells was driven by enhanced epithelial-mesenchymal transition, which was resulted from SNAI2 upregulation via the GSK-3ß/ß-catenin pathway. This study suggested that NAV2 could induce melanoma proliferation and invasion by epithelial-mesenchymal transition through the GSK-3ß/ß-catenin-SNAI2 pathway. Our findings on the pathological mechanisms of NAV2-associated cutaneous melanoma may contribute to the development of potential therapeutic strategy for melanoma.

CDC5L drives FAH expression to promote metabolic reprogramming in melanoma.

Metabolic reprogramming allows tumor cells to thrive in the typically hypoxic tumor microenvironment. Using immunodetection and clinical data analyses, we demonstrate here that fumarylacetoacetate hydrolase (FAH) is highly expressed in melanoma and correlates with poor survival. FAH knockdown inhibits proliferation and migration, while promoting apoptosis in melanoma cells, result in prolonged survival in tumor-bearing mice. Molecular analyses using real time RT-PCR, western blot, and 13C tracing showed that these changes are driven by strong stimulation of anaplerotic reactions through the TCA cycle and the pentose-phosphate pathway, resulting in increased fatty acid and nucleotide synthesis. Using bioinformatic, ChIP-PCR, and gene silencing analyses, we determined that cell division cycle 5-like protein (CDC5L) is an important transcription factor regulating FAH expression in melanoma cells. These findings reveal that FAH induces metabolic reprogramming in melanoma and so emerges as both a potentially useful independent prognostic indicator and an attractive therapeutic target.

Immunotherapy of HPV infection-caused genital warts using low dose cyclophosphamide.

Condylomata acuminata (CA), caused by human papillomavirus (HPV), is a common sexually transmitted disease with half a million new cases diagnosed in the United States per year and an annual increase in incidence in China. Conventional treatments, including topical cytotoxic agents, surgical excision and physical therapies, are traumatic, cause local side-effects and are invalid for subclinical or latent infection. Exploring immune approaches to eradicate HPV in CA therapeutics are highly desirable. Recent evidence shows that FOXP3(+) regulatory T (Treg) cells are accumulated in genital warts where they mediate immunosuppression. Intriguingly, a low dose of cyclophosphamide (CY), a conventional chemotherapy drug, can selectively target Treg cells, thereby enhancing the function of HPV-specific T cells and NK cells leading to efficient clearance of HPV infection. These findings have important clinical significance, and could potentially lead to a therapeutic breakthrough for the treatment of CA.

Low dosages: new chemotherapeutic weapons on the battlefield of immune-related disease.

Chemotherapeutic drugs eliminate tumor cells at relatively high doses and are considered weapons against tumors in clinics and hospitals. However, despite their ability to induce cellular apoptosis, chemotherapeutic drugs should probably be regarded more as a class of cell regulators than cell killers, if the dosage used and the fact that their targets are involved in basic molecular events are considered. Unfortunately, the regulatory properties of chemotherapeutic drugs are usually hidden or masked by the massive cell death induced by high doses. Recent evidence has begun to suggest that low dosages of chemotherapeutic drugs might profoundly regulate various intracellular aspects of normal cells, especially immune cells. Here, we discuss the immune regulatory roles of three kinds of chemotherapeutic drugs under low-dose conditions and propose low dosages as potential new chemotherapeutic weapons on the battlefield of immune-related disease.

Selective depletion of CD4+CD25+Foxp3+ regulatory T cells by low-dose cyclophosphamide is explained by reduced intracellular ATP levels.

CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells have been shown to play important roles in mediating cancer development. Although cyclophosphamide (CY) has shown promise as a drug to selectively target Treg cells with low-dose in vivo, the underlying molecular mechanism remains unclear. In this report, we provide evidence that ATP, the energy molecule and signal element, accounts for the selective depletion of Treg cells by low-dose CY. Relative to conventional T cells or other cell types, ATP levels were much lower in Treg cells. This was due to Treg cells that downregulate one microRNA, miR-142-3p, and upregulate ecto-nucleoside triphosphate diphosphohydrolase CD39. The transfection of miR-142-3p or the blockade of CD39 could increase intracellular ATP levels of Treg cells, consequently decreasing the sensitivity of Treg cells to low-dose CY. On the other hand, the transfection of miR-142-3p inhibitor or the addition of soluble CD39 to the cultured CD4(+)CD25(-) T cells resulted in the decrease of intracellular ATP levels and increase of sensitivity of conventional T cells to low-dose CY. Furthermore, we found that the low levels of ATP attenuated the synthesis of glutathione, leading to the decrease of CY detoxification, thus increasing the sensitivity of Treg cells to low-dose CY. Therefore, we here identify a molecular pathway through which low-dose CY selectively ablates Treg cells. Our findings also imply that low levels of ATP are probably related to Treg cell function.