-
Journal For Immunotherapy of Cancer May 2024The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been...
BACKGROUND
The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10-15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets.
METHODS
This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples.
RESULTS
A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3 DCs promote CD8 T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3 DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion.
CONCLUSION
Our findings expound valuable insights into the role of the interaction between LAMP3 DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.
Topics: Humans; Dendritic Cells; Thyroid Cancer, Papillary; Lysosomal-Associated Membrane Protein 3; Thyroid Neoplasms; Male; Female; Tumor Microenvironment; Middle Aged; Tumor Escape; T-Lymphocyte Subsets; Neoplasm Proteins
PubMed: 38816233
DOI: 10.1136/jitc-2024-008983 -
Clinics (Sao Paulo, Brazil) May 2024This study was directed towards exploring the impacts of lncRNA HOXA11-AS-mediated microRNA (miR)-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis...
OBJECTIVES
This study was directed towards exploring the impacts of lncRNA HOXA11-AS-mediated microRNA (miR)-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis (OA).
METHODS
The articular cartilages were provided by OA patients who received total knee arthroplasty, and Human Chondrocyte (HC)-OA (HCOA) was also attained. The miR-506-3p and HOXA11-AS expressions in articular cartilages from OA patients and HCOA cells were analyzed via qPCR. After gain- and loss-of-function assays in HCOA cells, MTT assay and flow cytometry (FC) were used for assessing cell viability and apoptosis, accordingly. The levels of PIK3CA, AKT, and mTOR as well as AKT and mTOR phosphorylation levels assessed using western blotting (WB). The targeting correlation of HOXA11-AS and miR-506-3p as well as miR-506-3p and PIK3CA was assessed through Dual-Luciferase Reporter gene Assay (DLRA).
RESULT
The articular cartilages from OA patients and Human Chondrocyte (HC)-OA (HCOA) cells showed increased HOXA11-AS and decreased miR-506-3p. Mechanistically, HOXA11-AS was capable of binding to miR-506-3p to increase PIK3CA, the target gene of miR-506-3p. miR-506-3p suppression facilitated HCOA cell proliferation and reduced their apoptosis, which was nullified by further silencing HOXA11-AS or silencing PIK3CA. The down-regulation of HOXA11-AS disrupted the PI3K/AKT/mTOR pathway, which was counteracted by further miR-506-3p inhibition.
CONCLUSION
The silencing of HOXA11-AS might block the PI3K/AKT/mTOR pathway through miR-506-3p up-regulation, thereby restricting HCOA cell proliferation and provoking apoptosis.
PubMed: 38815540
DOI: 10.1016/j.clinsp.2024.100393 -
PLoS Neglected Tropical Diseases May 2024Following the COVID-19 pandemic declaration, the World Health Organization recommended suspending neglected tropical diseases (NTD) control activities as part of...
BACKGROUND
Following the COVID-19 pandemic declaration, the World Health Organization recommended suspending neglected tropical diseases (NTD) control activities as part of sweeping strategies to minimise COVID-19 transmission. Understanding how NTD programs were impacted and resumed operations will inform contingency planning for future emergencies. This is the first study that documents how South-East Asian and Pacific NTD programs addressed challenges experienced during the COVID-19 pandemic.
METHODOLOGY/PRINCIPAL FINDINGS
Data was collected through semi-structured interviews with 11 NTD Program Coordinators and related personnel from Fiji, Papua New Guinea, The Philippines, Timor-Leste, and Vanuatu. Constructivist grounded theory methods were drawn on to generate an explanation of factors that enabled or hindered NTD program operations during the COVID-19 pandemic. The COVID-19 pandemic disrupted NTD programs in all countries. Some programs implemented novel strategies by partnering with services deemed essential or used new communications technology to continue (albeit scaled-back) NTD activities. Strong relationships to initiate cross-program integration, sufficient resources to implement adapted activities, and dedicated administrative systems were key enabling factors for recommencement. As the COVID-19 pandemic continued, exacerbating health resources scarcity, programs faced funding shortages and participants needed to find efficiencies through greater integration and activity prioritisation within their NTD units. Emphasising community-led approaches to restore trust and engagement was critical after widespread social anxiety and disconnection.
CONCLUSIONS/SIGNIFICANCE
Sustaining effective NTD programs during a global emergency goes beyond managing immediate activity disruptions and requires attention to how NTD programs can be better ensconced within wider health programs, administrative, and social systems. This study underscores the importance of pre-emergency planning that reinforces NTD control programs as a critical service at all health systems levels, accompanied by governance arrangements that increase NTD staff control over their operations and strategies to maintain strong community relationships. Ensuring NTD units are supported via appropriate funding, personnel, and bureaucratic resources is also required.
PubMed: 38814987
DOI: 10.1371/journal.pntd.0012221 -
PloS One 2024The skin microbiome maintains healthy human skin, and disruption of the microbiome balance leads to inflammatory skin diseases such as folliculitis and atopic...
The skin microbiome maintains healthy human skin, and disruption of the microbiome balance leads to inflammatory skin diseases such as folliculitis and atopic dermatitis. Staphylococcus aureus and Cutibacterium acnes are pathogenic bacteria that simultaneously inhabit the skin and cause inflammatory diseases of the skin through the activation of innate immune responses. Silkworms are useful invertebrate animal models for evaluating innate immune responses. In silkworms, phenoloxidase generates melanin as an indicator of innate immune activation upon the recognition of bacterial or fungal components. We hypothesized that S. aureus and C. acnes interact to increase the innate immunity-activating properties of S. aureus. In the present study, we showed that acidification is involved in the activation of silkworm hemolymph melanization by S. aureus. Autoclaved-killed S. aureus (S. aureus [AC]) alone does not greatly activate silkworm hemolymph melanization. On the other hand, applying S. aureus [AC] treated with C. acnes culture supernatant increased the silkworm hemolymph melanization. Adding C. acnes culture supernatant to the medium decreased the pH. S. aureus [AC] treated with propionic acid, acetic acid, or lactic acid induced higher silkworm hemolymph melanization activity than untreated S. aureus [AC]. S. aureus [AC] treated with hydrochloric acid also induced silkworm hemolymph melanization. The silkworm hemolymph melanization activity of S. aureus [AC] treated with hydrochloric acid was inhibited by protease treatment of S. aureus [AC]. These results suggest that acid treatment of S. aureus induces innate immune activation in silkworms and that S. aureus proteins are involved in the induction of innate immunity in silkworms.
Topics: Animals; Hemolymph; Bombyx; Staphylococcus aureus; Melanins; Immunity, Innate; Hydrogen-Ion Concentration; Monophenol Monooxygenase
PubMed: 38814922
DOI: 10.1371/journal.pone.0298502 -
Psychiatrike = Psychiatriki May 2024Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a...
Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a transient increase in glutamate release, leading to increases in neurotrophic signaling and restoration of synaptic function in brain regions involved in mood regulation and emotional behavior. Several randomized clinical trials have shown its effectiveness in reducing the symptoms of depression in some people, despite its short-term side effects that include mainly disorientation, dizziness, nausea, and increased blood pressure. In 2019, the United States Food and Drug Administration (FDA) as well as the European Medicines Agency approved the use of esketamine nasal spray in combination with an oral antidepressant for treatment-resistant depression in adults. Our study aimed to evaluate the effectiveness of this new therapeutic proposal in a case series of five Greek patients with treatment- resistant depression. Intranasal esketamine was administered under medical supervision in combination with an oral antidepressant. Depressive symptoms were evaluated at three time points (baseline, end of treatment, and one-year post-treatment) using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Patient Health Questionnaire (PHQ-9), the CGI Clinical Global Impression Scale, and the Perceived Deficits Questionnaire for Depression (PDQ-D). Possible side effects were assessed using the Richmond Suppression Agitation Scale (RASS), the Sheehan Disability Scale (SDS), the CADSS Disruptive States Scale, and a predefined list of adverse events (AEs) and serious adverse events (SAEs). Patients followed an individualized treatment plan for seven to twelve months depending on the achievement of an adequate response. Statistical analysis of the results revealed a significant improvement (p<0.05) on all scales used. All participants maintained their level of improvement at follow-up after twelve months. Adverse effects were found to be mild and tolerable. It is worth noting that significant side effects were reported only by the two patients with comorbid personality disorder. The results, despite limited to a small sample, indicate the positive effect of esketamine on the stable reduction of depressive symptoms among patients with resistant depression, even after the completion of treatment.
PubMed: 38814267
DOI: 10.22365/jpsych.2024.006 -
Frontiers in Psychology 2024With the growing array of challenges humanity has been experiencing since the global pandemic, knowledge workers at all levels of organizations are experiencing a noted...
With the growing array of challenges humanity has been experiencing since the global pandemic, knowledge workers at all levels of organizations are experiencing a noted increase in the volatility, uncertainty, complexity, and ambiguity (VUCA) conditions of their work and lives. This has brought about significant changes in ways of working and associated ways of being that have become more fragmented and virtual. Disruptive change continues to unfold on many levels of society, from the organizational to the individual level, with multiple and often unintended consequences. This article outlines how the body of work of Dynamic Presencing in a group coaching context facilitates responsive forms of personal development as well as a deeper transformation of one's leadership identity in the face of such change, which in turn serves as an approach that can be useful in navigating VUCA conditions that are becoming increasingly prevalent. The transformative process of Dynamic Presencing develops core inner leadership capabilities with a noted increase in the quality of internal and interpersonal forms of self-,presence-, and presencing-awareness. Overall, Dynamic Presencing serves as a critical enabler of presencing mastery, which instills deeper confidence and resourcefulness in working with the VUCA conditions of our global world by deepening our presencing process and refining our methods for inner leadership development in turbulent times.
PubMed: 38813560
DOI: 10.3389/fpsyg.2024.1352828 -
Turkish Journal of Medical Sciences 2023Temporomandibular Disorders (TMD), as in the occurrence of many diseases, have been associated with oxidative stress (OS) resulting from the disruption of antioxidant...
BACKGROUND/AIM
Temporomandibular Disorders (TMD), as in the occurrence of many diseases, have been associated with oxidative stress (OS) resulting from the disruption of antioxidant mechanisms and the accumulation of reactive oxygen species in tissues. This study was designed to compare salivary and serum OS and inflammation markers of individuals with TMD and healthy subjects.
MATERIALS AND METHODS
A prospective cross-sectional study was conducted. Twenty-seven TMD patients diagnosed with disc displacement (DD) according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and 17 healthy subjects were enrolled in the study. Prior to any treatment, serum, and saliva samples were taken from the patients and centrifuged, and stored at -80 °C until analyzed. All samples were examined for Interleukin-6 (IL-6), Malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) concentrations.
RESULTS
There was no significant difference between the groups regarding median values of 8-OHdG, IL-6, and MDA (p > 0.05). When the relationship between serum and salivary 8-OHdG, IL-6, and MDA levels in all subjects was evaluated, there was a strong positive correlation between the levels of 8-OHdG and IL-6 in the serum (r = 0.752, p <0.001). In the study group, when the relationship between pain levels and serum and saliva 8-OHdG, IL-6, and MDA levels was assessed, a positive and strong correlation was found between the levels of 8-OHdG and IL-6 in serum.
CONCLUSION
Although the strong correlation between pain scores and serum 8-OHdG and MDA levels supports the hypothesis that inflammation and OS mechanisms may be interrelated, according to the results of the study, inflammatory and OS markers in patients with TMD were not different from healthy individuals.
Topics: Humans; Oxidative Stress; Saliva; Temporomandibular Joint Disorders; Female; Adult; Male; Cross-Sectional Studies; Biomarkers; Interleukin-6; Prospective Studies; Malondialdehyde; Inflammation; 8-Hydroxy-2'-Deoxyguanosine; Young Adult; Middle Aged
PubMed: 38813510
DOI: 10.55730/1300-0144.5737 -
Frontiers in Public Health 2024This research investigated the impact of the COVID-19 pandemic on the mental well-being and sleep quality of students in higher vocational colleges in Sichuan, China,...
PURPOSE
This research investigated the impact of the COVID-19 pandemic on the mental well-being and sleep quality of students in higher vocational colleges in Sichuan, China, identifying key factors influencing their psychological health during this period.
METHODS
Between January and February 2022, a comprehensive survey was conducted among students from several higher vocational colleges in Sichuan, utilizing a randomized selection approach to involve 3,300 participants. Data were collected through direct interviews executed by skilled interviewers.
RESULTS
Out of 3,049 valid responses, a significant number reported experiencing symptoms of poor mental health, anxiety, depression, and insomnia, with prevalence rates of 21.2%, 9.7%, 14.1%, and 81.9%, respectively. Factors contributing positively to mental health and sleep included a higher family economic status, reduced stress from the pandemic, and decreased online activity. Conversely, lack of physical activity post-pandemic, disruptions to education and employment, and deteriorating relationships emerged as negative influencers. Interestingly, a lack of pre-pandemic mental health knowledge acted as a protective factor against insomnia.
CONCLUSION
The ongoing management of COVID-19 has notably influenced the psychological and sleep health of vocational college students, driven by economic, emotional, lifestyle, and educational factors. The findings underscore the necessity for targeted interventions to address these challenges effectively.
Topics: Humans; COVID-19; China; Male; Students; Female; Universities; Mental Health; Young Adult; Sleep Quality; Adult; Surveys and Questionnaires; Sleep Initiation and Maintenance Disorders; Depression; Anxiety; Adolescent; SARS-CoV-2; Prevalence
PubMed: 38813405
DOI: 10.3389/fpubh.2024.1387247 -
Heliyon May 2024Microplastics (MPs) are pervasive pollutants exuded from anthropogenic activities and ingested by animals in different ecosystems. This transcriptomic profiling study...
Microplastics (MPs) are pervasive pollutants exuded from anthropogenic activities and ingested by animals in different ecosystems. This transcriptomic profiling study aimed to explore the impact of polyethylene MPs on , an ecologically significant bivalve species. The toxicity of two MPs types was found to result in increased cellular stress when exposed up to 14 days. Moreover, recovery mechanisms were also observed in progress. Mussels exhibited different gene expression patterns and molecular regulation in response to cellular reactive oxygen species (ROS) stress. The transcriptome analysis demonstrated a notable hindrance in cilia movement as MPs ingested through gills. Subsequent entry resulted in a significant disruption in the cytoskeletal organization, cellular projection, and cilia beat frequency. On day 4 (D4), signal transduction and activation of apoptosis evidenced the signs of toxic consequences. Mussels exposed to spherical MPs shown significant recovery on day 14 (D14), characterized by the upregulation of anti-apoptotic genes and antioxidant genes. The expression of P53 and BCL2 genes was pivotal in controlling the apoptotic process and promoting cell survival. Mussels exposed to fibrous MPs displayed a delayed cell survival effect. However, the elevated physiological stress due to fibrous MPs resulted in energy transfer by compensatory regulation of metabolic processes to expedite cellular recovery. These observations highlighted the intricate and varied reaction of cell survival mechanisms in mussels to recover toxicity. This study provides critical evidence of the ecotoxicological impacts of two different MPs and emphasizes the environmental risks they pose to aquatic ecosystems. Our conclusion highlights the detrimental effects of MPs on and the need for more stringent regulations to protect marine ecosystems.
PubMed: 38813215
DOI: 10.1016/j.heliyon.2024.e30858 -
The bone nonunion microenvironment: A place where osteogenesis struggles with osteoclastic capacity.Heliyon May 2024Bone nonunion is a common and serious orthopedic disorder, the occurrence of which is associated with a disruption of the dynamic balance between osteoblasts and... (Review)
Review
Bone nonunion is a common and serious orthopedic disorder, the occurrence of which is associated with a disruption of the dynamic balance between osteoblasts and osteoclasts during bone repair. However, the critical molecular mechanisms affecting this homeostasis are not well understood, and it is essential to investigate the specific components of this mechanism and to restore the balance between osteoblasts and osteoclasts to promote bone repair. First, we defined this complex local environmental factor as the "bone nonunion microenvironment" and identified the importance of the "struggle" between osteoblasts and osteoclasts, which is the most essential element in determining the process of . On this basis, we also explored the cellular factors that influence osteogenesis and the molecular signals that influence the balance between and osteoblasts, which are important for restoring homeostasis. Further, we explored other factors involved in osteogenesis, such as the biomechanical environment, the nutritional environment, the acid-base environment, and the temperature environment, which are important players in osteogenesis. In conclusion, we found that the balance between osteoblasts and osteoclasts is the essence of bone healing, which is based on the "bone nonunion microenvironment". Therefore, investigating the role of the bone nonunion microenvironment in the system of osteoblast-osteoclast "struggle" provides an important basis for further understanding of the mechanism of nonunion and the development of new therapeutic approaches.
PubMed: 38813209
DOI: 10.1016/j.heliyon.2024.e31314