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The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response.

Newly discovered anti-cancer immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cells, focus on spurring the anti-tumor effector T cell (Teff) response. Although such strategies have already demonstrated a sustained beneficial effect in certain malignancies, a substantial proportion of treated patients does not respond. CD4+FOXP3+ regulatory T cells (Tregs), a suppressive subset of T cells, can impair anti-tumor responses and reduce the efficacy of currently available immunotherapies. An alternative view that has emerged over the last decade proposes to tackl

New insights into the phenomenon of remissions and relapses in autoimmune diseases and the puzzle of benign autoantibodies in healthy individuals.

The onset and relapse of autoimmune diseases (AIDs) are triggered by autoimmune attacks on target tissues. However, symptoms are unlikely to appear if damaged cells are rapidly replaced. Addressing the implications of this premise, the present work examines the balance between target tissue destruction and recovery rates as a key factor in the mechanisms of remissions and relapses in AIDs. The theory, supported by published clinical data, suggests that remissions are improbable in AIDs characterized by slow target tissue recovery. Conversely, a high recovery rate is a necessary (though not suf

Retrospective Analysis of Clinicopathological Characteristics of Lacrimal Gland Pleomorphic Adenoma and Mechanism of Tumorigenesis by the Imbalance Between Apoptosis and Proliferation.

BACKGROUND Lacrimal gland pleomorphic adenoma (LGPA) is the most common clinically benign epithelial tumor of the lacrimal gland and is predominantly comprised of epithelial cells and interstitial components. At present, the exact pathogenesis of LGPA remains unclear. Previous research has indicated that the occurrence of LGPA may be related to excessive cell proliferation. MATERIAL AND METHODS This study observed the clinicopathological characteristics of LGPA and investigated the tumorigenesis mechanism of cell over-proliferation caused by the imbalance between apoptosis and proliferation. A

Inflammation in cancer: therapeutic opportunities from new insights.

As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors

Exploring cellular diversity in lung adenocarcinoma epithelium: Advancing prognostic methods and immunotherapeutic strategies.

Immunotherapy has brought significant advancements in the treatment of lung adenocarcinoma (LUAD), but identifying suitable candidates remains challenging. In this study, we investigated tumour cell heterogeneity using extensive single-cell data and explored the impact of different tumour cell cluster abundances on immunotherapy in the POPLAR and OAK immunotherapy cohorts. Notably, we found a significant correlation between CKS1B+ tumour cell abundance and treatment response, as well as stemness potential. Leveraging marker genes from the CKS1B+ tumour cell cluster, we employed machine learnin

Googling the Guggul (Commiphora and Boswellia) for Prevention of Chronic Diseases.

Extensive research during last 2 decades has revealed that most drugs discovered today, although costs billions of dollars for discovery, and yet they are highly ineffective in their clinical response. For instance, the European Medicines Agency has approved 68 anti-cancer drugs, and out of which 39 has reached the market level with no indication of increased survival nor betterment of quality of life. Even when drugs did improve survival rate compared to available treatment strategies, most of these were found to be clinically insignificant. This is a fundamental problem with modern drug disc

Acute kidney injury: pathogenesis and therapeutic interventions.

Acute kidney injury (AKI) is a prevalent clinical condition that is associated with unacceptably high morbidity and mortality, as well as the development of chronic kidney disease (CKD). The pathogenesis of AKI is highly complex and heterogeneous, primarily attributed to metabolic disturbances arising from the disease itself and the administration of medications related to treatment. In recent years, AKI in cancer patients is highly concerned. The emergence of AKI caused injuries and dysfunction of remote organs but also enhanced the health-care costs. It's essential for early recognition of A

Role of exosomes in pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies. Exosomes, which are released by multiple cell types, such as cancer cells, contain functional biomolecules (including proteins, nucleic acids and lipids) that can be horizontally delivered to recipient cells. Exosomes act as the most prominent mediator of intercellular communication and can regulate, instruct and re-educate their surrounding microenvironment and target specific organs. The present review performed an extensive search of multiple databases from 2005 to April 23 2017, for eligible literature relating to exosomes and their

Cellular senescence-from solid organs to vascularized composite allotransplants.

Vascularized composite allotransplantation (VCA) has emerged as a novel therapy approach to restore form and function in patients with severe tissue defects of the face, hand, and abdominal wall, among other anatomical regions. The composite allografts comprise different tissues such as skin, muscle, or bone. Clinical data demonstrate promising mid- and long-term outcomes following VCA surgery, but our understanding of the cellular interactions and molecular pathways in VCA surgery is oftentimes deduced from solid organ transplantation (SOT). In SOT, the concept of cellular senescence has grow

Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is characterized by exposed necrotic bone that often progresses with increasing pain and impaired quality of life. Zoledronate, the most potent and widely used bisphosphonate, has been strongly associated with BRONJ development following invasive dental procedures. Given the rising incidence of BRONJ, understanding and implementing effective preventive strategies have become imperative. Biomaterials based on synthetic hydroxyapatite and beta-tricalcium phosphate have been investigated as potential preventive agents. Their therapeutic rati

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… Histological Evaluation Zoledronate impairs soft tissue healing by inhibiting collagen expression in oral fibroblasts, a process essential for re-epithelialization. This represents a well-established mechanism underlying mucosal breakdown and bone exposure in BRONJ. …

The role of autophagy in cancer: from molecular mechanism to therapeutic window.

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy a

Management of Foot Ulcers and Chronic Wounds with Amniotic Membrane in Comorbid Patients: A Successful Experience.

Chronic wounds are defined as those with disturbances in normal healing. They involve symptoms like exudate, odor, pain or impaired mobility, severely impacting life quality. In the case of patients with additional comorbidities, these are known to aggravate the healing impairment. Amniotic membrane (AM) is gaining attention for its regenerative potential, as it has shown promise in treating hard-to-heal wounds, such as diabetic foot ulcers. This work examines a series of five patients who, while suffering an array of other chronic conditions, were treated with AM for the management of non-hea

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… Chronic Wound Healing by Amniotic Membrane: TGF-β and EGF Signaling Modulation in Re-Epithelialization Front. Bioeng. Biotechnol. 2021 9 689328 10.3389/fbioe.2021.689328 34295882 PMC8290337 11. Hasegawa T. Mizoguchi M. Haruna K. Mizuno Y. Muramatsu S. Suga Y. Ogawa H. Ikeda S. …

From Pathogenesis to Intervention: The Importance of the Microbiome in Oral Mucositis.

Oral mucositis (OM) is a common and impactful toxicity of standard cancer therapy, affecting up to 80% of patients. Its aetiology centres on the initial destruction of epithelial cells and the increase in inflammatory signals. These changes in the oral mucosa create a hostile environment for resident microbes, with oral infections co-occurring with OM, especially at sites of ulceration. Increasing evidence suggests that oral microbiome changes occur beyond opportunistic infection, with a growing appreciation for the potential role of the microbiome in OM development and severity. This review c

Anti-Tumor Effects of Low Dose Zoledronate on Lung Cancer-Induced Spine Metastasis.

Zoledronate (Zol) is an anti-resorptive/tumoral agent used for the treatment of many cancers including spinal bone metastasis. High systemic administration of a single dose is now the standard clinical care, yet it has been associated with several side effects. Here, we aimed to evaluate the effects of lower doses Zol on lung cancer and lung cancer-induced bone metastasis cells over a longer time period. Human lung cancer (HCC827) and three bone metastases secondary to lung cancer (BML1, BML3 and BML4) cells were treated with Zol at 1, 3 and 10 µM for 7 days and then assessed for cell prolifer

Effect of recombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy.

IntroductionNeurotrophic Keratopathy (NK) is a neurodegenerative corneal disease that results in diminished corneal sensation. Previous studies have found that Cenegermin 0.002%, a recombinant human nerve growth factor (rhNGF), improves corneal epithelial healing in stage 2 and 3 NK patients. However, rhNGF effect on corneal sensation and nerve regeneration has not been well established. Thus, this study aims to analyze the effect of rhNGF on corneal nerve regeneration using in vivo confocal microscopy (IVCM) and on corneal sensitivity in NK patients.MethodsThis is a retrospective, longitudina

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

BACKGROUND: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). METHODS: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 week

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… Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16. J Cell Biol. 1996;132(3):381–397. doi: 10.1083/jcb.132.3.381. 41. Chen C, Zhang Q, Yu W, Chang B, Le AD. …

Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science.

Traditional Chinese medicine (TCM) has been practiced for thousands of years and at the present time is widely accepted as an alternative treatment for cancer. In this review, we sought to summarize the molecular and cellular mechanisms underlying the chemopreventive and therapeutic activity of TCM, especially that of the Chinese herbal medicine-derived phytochemicals curcumin, resveratrol, and berberine. Numerous genes have been reported to be involved when using TCM treatments and so we have selectively highlighted the role of a number of oncogene and tumor suppressor genes in TCM therapy. I

Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.

Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regard

STAT3 pathway in cancers: Past, present, and future.

Signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, discovered in the cytoplasm of almost all types of mammalian cells, plays a significant role in biological functions. The duration of STAT3 activation in normal tissues is a transient event and is strictly regulated. However, in cancer tissues, STAT3 is activated in an aberrant manner and is induced by certain cytokines. The continuous activation of STAT3 regulates the expression of downstream proteins associated with the formation, progression, and metastasis of cancers. Thus, elucidating the mechanisms o