Application of Nuc-mtDNA and DNA methylation analysis in life science and medical studies

To appreciate the two significant findings,namely the independent confirmation of the existence of Neanderthal genes in modern humans in 2010,and a clear description of the genetic history of an archaic hominin group from Denisova Cave in Siberia in 2010,the 2022 Nobel Prize for Medicine and Physiology was recently awarded to Dr.Svante Paabo[1].This year’s Nobel prize recognized the value of molecular paleoanthropology,which investigates the past of human beings.The application of this genetic analysis is even more valuable to our present and future.

Photothermal Nano-Vaccine Promoting Antigen Presentation and Dendritic Cells Infiltration for Enhanced Immunotherapy of Melanoma via Transdermal Microneedles Delivery

Immunotherapy has demonstrated the potential to cure melanoma,while the current response rate is still unsatisfactory in clinics.Extensive evidence indicates the correlation between the eficacy and pre-existing T-cell in tumors,whereas the baseline T-cell infiltration is lacking in low-response melanoma patients.

Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation of iron-dependent membranelocalized lipid peroxides.It acts as an innate tumor suppressor mechanism and participates in the biological processes of tumors.Intriguingly,mesenchymal and dedifferentiated cancer cells,which are usually resistant to apoptosis and traditional therapies,are exquisitely vulnerable to ferroptosis,further underscoring its potential as a treatment approach for cancers,especially for refractory cancers.However,the impact of ferroptosis on cancer extends beyond its direct cytotoxic effect on tumor cells.Ferroptosis induction not only inhibits cancer but also promotes cancer development due to its potential negative impact on anticancer immunity.Thus,a comprehensive understanding of the role of ferroptosis in cancer is crucial for the successful translation of ferroptosis therapy from the laboratory to clinical applications.In this review,we provide an overview of the recent advancements in understanding ferroptosis in cancer,covering molecular mechanisms,biological functions,regulatory pathways,and interactions with the tumor microenvironment.We also summarize the potential applications of ferroptosis induction in immunotherapy,radiotherapy,and systemic therapy,as well as ferroptosis inhibition for cancer treatment in various conditions.We finally discuss ferroptosis markers,the current challenges and future directions of ferroptosis in the treatment of cancer.

Signaling pathways and targeted therapies for psoriasis

Psoriasis is a common,chronic,and inflammatory skin disease with a high burden on individuals,health systems,and society worldwide.With the immunological pathologies and pathogenesis of psoriasis becoming gradually revealed,the therapeutic approaches for this disease have gained revolutionary progress.Nevertheless,the mechanisms of less common forms of psoriasis remain elusive.Furthermore,severe adverse effects and the recurrence of disease upon treatment cessation should be noted and addressed during the treatment,which,however,has been rarely explored with the integration of preliminary findings.Therefore,it is crucial to have a comprehensive understanding of the mechanisms behind psoriasis pathogenesis,which might offer new insights for research and lead to more substantive progress in therapeutic approaches and expand clinical options for psoriasis treatment.In this review,we looked to briefly introduce the epidemiology,clinical subtypes,pathophysiology,and comorbidities of psoriasis and systematically discuss the signaling pathways involving extracellular cytokines and intracellular transmission,as well as the cross-talk between them.In the discussion,we also paid more attention to the potential metabolic and epigenetic mechanisms of psoriasis and the molecular mechanistic cascades related to its comorbidities.This review also outlined current treatment for psoriasis,especially targeted therapies and novel therapeutic strategies,as well as the potential mechanism of disease recurrence.

A piezoelectric-driven microneedle platform for skin disease therapy

With over a million cases detected each year,skin disease is a global public health problem that diminishes the quality of life due to its difficulty to eradicate,propensity for recurrence,and potential for post-treatment scarring.Photodynamic therapy(PDT)is a treatment with minimal invasiveness or scarring and few side effects,making it well tolerated by patients.However,this treatment requires further research and development to improve its effective clinical use.Here,a piezoelectric-driven microneedle(PDMN)platform that achieves high efficiency,safety,and non-invasiveness for enhanced PDT is proposed.This platform induces deep tissue cavitation,increasing the level of protoporphyrin IX and significantly enhancing drug penetration.A clinical trial involving 25 patients with skin disease was conducted to investigate the timeliness and efficacy of PDMN-assisted PDT(PDMN-PDT).Our findings suggested that PDMN-PDT boosted treatment effectiveness and reduced the required incubation time and drug concentration by 25%and 50%,respectively,without any anesthesia compared to traditional PDT.These findings suggest that PDMN-PDT is a safe and minimally invasive approach for skin disease treatment,which may improve the therapeutic efficacy of topical medications and enable translation for future clinical applications.

CD147 Facilitates the Pathogenesis of Psoriasis through Glycolysis and H3K9me3 Modification in Keratinocytes

Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal cells.Although elevated glycolysis flux has been reported in psoriasis,the molecular mechanisms underlying its pathogenesis remain unclear.We investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis,observing its high expression in psoriatic skin lesions of humans and imiquimod(IMQ)-induced mouse models.In mouse models,genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic inflammation.We found that CD147 interacted with glucose transporter 1(Glut1).Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in vivo.In CD147-knockout mice and keratinocytes,oxidative phosphorylation was increased in the epidermis,indicating CD147's pivotal role in glycolysis reprogramming during pathogenesis of psoriasis.Using non-targeted and targeted metabolic techniques,we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid(α-KG).

黑色素瘤的免疫检查点阻断疗法

Melanoma,a type of skin malignancy with a high incidence and poor prognosis,is a global public health issue.The tumorigenesis and pathogenesis of melanoma involve genetic mutations,metabolic disruption,and immune evasion.Tumors undergo immune editing to escape immune surveillance,and immune escape has been identified as a critical factor in the development and progression of melanoma.

Sphingosine kinase 1 promotes tumor immune evasion by regulating the MTA3-PD-L1 axis

Immune checkpoint blockade(ICB)exhibits considerable benefits in malignancies,but its overall response rate is limited.Previous studies have shown that sphingosine kinases(SPHKs)are critical in the tumor microenvironment(TME),but their role in immunotherapy is unclear.We performed integrative analyses including bioinformatics analysis,functional study,and clinical validation to investigate the role of SPHK1 in tumor immunity.Functionally,we demonstrated that the inhibition of SPHK1 significantly suppressed tumor growth by promoting antitumor immunity in immunocompetent melanoma mouse models and tumor T-cell cocultures.A mechanistic analysis revealed that MTA3 functions as the downstream target of SPHK1 in transcriptionally regulating tumor PD-L1.Preclinically,we found that anti-PD-1 monoclonal antibody(mAb)treatment significantly rescued tumor SPHK1 overexpression or tumor MTA3 overexpression-mediated immune evasion.Significantly,we identified SPHK1 and MTA3 as biological markers for predicting the efficacy of anti-PD-1 mAb therapy in melanoma patients.Our findings revealed a novel role for SPHK1 in tumor evasion mediated by regulating the MTA3-PD-L1 axis,identified SPHK1 and MTA3 as predictors for assessing the efficacy of PD-1 mAb treatment,and provided a therapeutic possibility for the treatment of melanoma patients.