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Frontiers in Aging 2024Hyperbaric Oxygen Therapy (HBOT) utilizes 100% oxygen at high atmospheric pressure for clinical applications. HBOT has proven to be an effective supplementary treatment... (Review)
Review
Hyperbaric Oxygen Therapy (HBOT) utilizes 100% oxygen at high atmospheric pressure for clinical applications. HBOT has proven to be an effective supplementary treatment for a variety of clinical and pathological disorders. HBOT's therapeutic results are based on the physiological effects of increased tissue oxygenation, or improved oxygen bioavailability. HBOT's current indications in illnesses like as wound healing, thermal or radiation burns, and tissue necrosis point to its function in facilitating the regeneration process. Various research has revealed that HBOT plays a function in vascularization, angiogenesis, and collagen production augmentation. Individual regeneration capacity is influenced by both environmental and genetic factors. Furthermore, the regenerating ability of different types of tissues varies, and this ability declines with age. HBOT affects physiological processes at the genetic level by altering gene expression, delaying cell senescence, and assisting in telomere length enhancement. The positive results in a variety of indications, ranging from tissue regeneration to better cognitive function, indicate that it has enormous potential in regenerative and anti-aging therapy.
PubMed: 38757145
DOI: 10.3389/fragi.2024.1368982 -
Gut May 2024Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known...
OBJECTIVE
Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies.
DESIGN
We used the KPC mouse model () and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent coculture assays, mouse and zebrafish tumorigenesis studies, and database approaches were performed.
RESULTS
Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC.
CONCLUSIONS
This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy.
PubMed: 38754953
DOI: 10.1136/gutjnl-2023-330995 -
Stroke Jul 2024Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the... (Comparative Study)
Comparative Study
BACKGROUND
Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site.
METHODS
Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality.
RESULTS
From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (=0.312) but did with functional independence (=0.010), with a similar trend on excellent outcome (=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score (=0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 (=0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM.
CONCLUSIONS
Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage.
Topics: Humans; Female; Male; Aged; Endovascular Procedures; Retrospective Studies; Middle Aged; Aged, 80 and over; Infarction, Posterior Cerebral Artery; Treatment Outcome; Case-Control Studies; Severity of Illness Index; Ischemic Stroke; Thrombolytic Therapy; Stroke
PubMed: 38753954
DOI: 10.1161/STROKEAHA.124.047383 -
World Journal of Oncology Jun 2024This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent...
BACKGROUND
This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent base of tongue and floor of mouth cancer.
METHODS
Thirty-one patients with recurrent lingual and floor of mouth squamous cell carcinoma after surgery and radiotherapy were treated with 3DPT-guided RSBT from 2015 to 2022. Seeds were implanted through a submental approach guided by 3DPTs. Local control (LC), overall survival (OS), disease control (DC) and quality of life (QOL) were evaluated.
RESULTS
The median follow-up was 13.7 months. The 1-, 3- and 5-year LC rates were 66.1%, 66.1%, and 55.1% respectively. The 1-, 3- and 5-year OS rates were 63.4%, 33.4%, and 8.3%. The 1-, 3- and 5-year DC rates were 37.8%, 26.5%, and 21.2%. Univariate analysis showed tumor size significantly affected LC (P = 0.031). The presence of extraterritorial lesions affected DC and OS on multivariate analysis (P < 0.01). QOL improved significantly in domains of pain, swallowing, chewing, taste, and emotion after treatment compared to baseline. Four patients (13%) developed necrosis and osteoradionecrosis.
CONCLUSIONS
3DPT-guided submental RSBT provided favorable LC and QOL for recurrent tongue/floor of mouth cancer with minimal toxicity; moreover, severe toxicity should be noted.
PubMed: 38751702
DOI: 10.14740/wjon1775 -
Brain Tumor Research and Treatment Apr 2024Delayed cerebral necrosis is a well-known complication of radiation therapy (RT). Because of its irreversible nature, it should be avoided if possible, but avoidance...
Delayed cerebral necrosis is a well-known complication of radiation therapy (RT). Because of its irreversible nature, it should be avoided if possible, but avoidance occurs at the expense of potentially compromised tumor control, despite the use of the modern advanced technique of conformal RT that minimizes radiation to normal brain tissue. Risk factors for radiation-induced cerebral necrosis include a higher dose per fraction, larger treatment volume, higher cumulative dose, and shorter time interval (for re-irradiation). The same principle can be applied to proton beam therapy (PBT) to avoid delayed cerebral necrosis. However, conversion of PBT radiation energy into conventional RT is still short of clinical support, compared to conventional RT. Herein, we describe two patients with excessively delayed cerebral necrosis after PBT, in whom follow-up MRI showed no RT-induced changes prior to 3 years after treatment. One patient developed radiation necrosis at 4 years after PBT to the resection cavity of an astroblastoma, and the other developed brainstem necrosis that became symptomatic 6 months after its first appearance on the 3-year follow-up brain MRI. We also discuss possible differences between radiation changes after PBT versus conventional RT.
PubMed: 38742264
DOI: 10.14791/btrt.2024.0017 -
Radiotherapy and Oncology : Journal of... May 2024Xerostomia, caused by radiation-induced parotid damage, is the most commonly reported radiotherapy (RT) complication for nasopharyngeal carcinoma (NPC). The purpose of...
BACKGROUND AND PURPOSE
Xerostomia, caused by radiation-induced parotid damage, is the most commonly reported radiotherapy (RT) complication for nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the value of intravoxel incoherent motion (IVIM) MR in monitoring radiation-induced parotid gland damage and predicting the risk of xerostomia.
METHODS
Fifty-four NPC patients were enrolled and underwent at least three IVIM MR scans: before (pre-RT), after 5 fractions of (5th-RT), halfway through (mid-RT), and after RT (post-RT). The degree of xerostomia patients was assessed before each MR examination. Furthermore, the time when patients first reported xerostomia symptoms was recorded. The changes in IVIM parameters throughout RT, as well as the relationships between IVIM parameters and xerostomia, were analysed.
RESULT
All IVIM parameters increased significantly from pre-RT to post-RT (p < 0.001). The rates of D, D* and f increase increased significantly from pre-RT to mid-RT (p < 0.001), indicating that cell necrosis mainly occurs in the first half of RT. In multivariate analysis, N3 (p = 0.014), pre-D (p = 0.007) and pre-D* (p = 0.003) were independent factors influencing xerostomia. D and f were significantly higher at 5th-RT than at pre-RT (both p < 0.05). IVIM detected parotid gland injury at 5th-RT at an average scanning time of 6.18 ± 1.07 days, earlier than the 11.94 ± 2.61 days when the patient first complained of xerostomia according to the RTOG scale (p < 0.001).
CONCLUSIONS
IVIM MR can dynamically monitor radiation-induced parotid gland damage and assess it earlier and more objectively than RTOG toxicity. Moreover, IVIM can screen people at risk of more severe xerostomia early.
PubMed: 38734144
DOI: 10.1016/j.radonc.2024.110323 -
Plants (Basel, Switzerland) Apr 2024genes () and () play a regulatory role in cuticle organization. Because the cuticle is a key evolutionary acquisition of plants for protection against environmental...
genes () and () play a regulatory role in cuticle organization. Because the cuticle is a key evolutionary acquisition of plants for protection against environmental factors, a knockout (KO) of each gene may alter their ability to adapt to unfavorable conditions. A potential pleiotropic effect of or gene mutations can be assessed under salt stress. Initial developmental stages are the most sensitive in living organisms; therefore, we evaluated salt tolerance of KO and KO barley lines at the seedling stage. Air-dried barley grains of the KO lines and of a wild-type (WT) line were germinated in NaCl solutions (50, 100, or 150 mM). Over 30 physiological and morphological parameters of seedlings were assessed. Potential pleiotropic effects of the gene KO under salt stress included the stimulation of root growth (which was lower under control conditions) and root necrosis. The pleiotropic effects of the gene KO under the stressful conditions manifested themselves as maintenance of longer root length as compared to the other lines; stable variation of most of morphological parameters; lack of correlation between root lengths before and after exposure to NaCl solutions, as well as between shoot lengths; and the appearance of twins. Salt tolerance of the analyzed barley lines could be ranked as follows: KO > KO ≈ WT, where KO lines were the most salt-tolerant. A comparison of effects of salinity and ionizing radiation on KO and KO barley lines indicated differences in tolerance of the lines to these stressors.
PubMed: 38732384
DOI: 10.3390/plants13091169 -
International Journal of Molecular... Apr 2024Monitoring inflammatory cytokines is crucial for assessing healing process and photobiomodulation (PBM) enhances wound healing. Meanwhile, cAMP response element-binding...
Investigating the Relevance of Cyclic Adenosine Monophosphate Response Element-Binding Protein to the Wound Healing Process: An In Vivo Study Using Photobiomodulation Treatment.
Monitoring inflammatory cytokines is crucial for assessing healing process and photobiomodulation (PBM) enhances wound healing. Meanwhile, cAMP response element-binding protein (CREB) is a regulator of cellular metabolism and proliferation. This study explored potential links between inflammatory cytokines and the activity of CREB in PBM-treated wounds. A total of 48 seven-week-old male SD rats were divided into four groups (wound location, skin or oral; treatment method, natural healing or PBM treatment). Wounds with a 6 mm diameter round shape were treated five times with an 808 nm laser every other day (total 60 J). The wound area was measured with a caliper and calculated using the elliptical formula. Histological analysis assessed the epidermal regeneration and collagen expression of skin and oral tissue with H&E and Masson's trichrome staining. Pro-inflammatory (TNF-α) and anti-inflammatory (TGF-β) cytokines were quantified by RT-PCR. The ratio of phosphorylated CREB (p-CREB) to unphosphorylated CREB was identified through Western blot. PBM treatment significantly reduced the size of the wounds on day 3 and day 7, particularly in the skin wound group ( < 0.05 on day 3, < 0.001 on day 7). The density of collagen expression was significantly higher in the PBM treatment group (in skin wound, < 0.05 on day 3, < 0.001 on day 7, and < 0.05 on day 14; in oral wound, < 0.01 on day 7). The TGF-β/TNF-α ratio and the p-CREB/CREB ratio showed a parallel trend during wound healing. Our findings suggested that the CREB has potential as a meaningful marker to track the wound healing process.
Topics: Animals; Wound Healing; Low-Level Light Therapy; Male; Rats; Cyclic AMP Response Element-Binding Protein; Rats, Sprague-Dawley; Skin; Cytokines; Phosphorylation; Tumor Necrosis Factor-alpha; Collagen; Transforming Growth Factor beta
PubMed: 38732058
DOI: 10.3390/ijms25094838 -
International Journal of Molecular... Apr 2024UVB radiation is known to induce photodamage to the skin, disrupt the skin barrier, elicit cutaneous inflammation, and accelerate the aging process. Murill (ABM) is an...
UVB radiation is known to induce photodamage to the skin, disrupt the skin barrier, elicit cutaneous inflammation, and accelerate the aging process. Murill (ABM) is an edible medicinal and nutritional fungus. One of its constituents, Murill polysaccharide (ABP), has been reported to exhibit antioxidant, anti-inflammatory, anti-tumor, and immunomodulatory effects, which suggests potential effects that protect against photodamage. In this study, a UVB-induced photodamage HaCaT model was established to investigate the potential reparative effects of ABP and its two constituents (A1 and A2). Firstly, two purified polysaccharides, A1 and A2, were obtained by DEAE-52 cellulose column chromatography, and their physical properties and chemical structures were studied. A1 and A2 exhibited a network-like microstructure, with molecular weights of 1.5 × 10 Da and 6.5 × 10 Da, respectively. The effects of A1 and A2 on cell proliferation, the mitochondrial membrane potential, and inflammatory factors were also explored. The results show that A1 and A2 significantly promoted cell proliferation, enhanced the mitochondrial membrane potential, suppressed the expression of inflammatory factors interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), and increased the relative content of filaggrin (FLG) and aquaporin-3 (AQP3). The down-regulated JAK-STAT signaling pathway was found to play a role in the response to photodamage. These findings underscore the potential of ABP to ameliorate UVB-induced skin damage.
Topics: Agaricus; Humans; Ultraviolet Rays; HaCaT Cells; Filaggrin Proteins; Cell Proliferation; Membrane Potential, Mitochondrial; Fungal Polysaccharides; Polysaccharides; Keratinocytes; Cytokines
PubMed: 38731895
DOI: 10.3390/ijms25094676 -
Cancers Apr 2024to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis.
PURPOSE
to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis.
METHODS
This is a monocentric prospective cohort of patients treated by SRT, followed by a brain MRI every two months. Subsequent SRT could be delivered in cases of new BMs during follow-up. The main endpoints were local control rate (LCR), overall survival (OS), and strategy success rate (SSR). Acute and late toxicity were evaluated.
RESULTS
Seventy patients were included from October 2014 to January 2019, and the most frequent primary diagnosis was non-small-cell lung cancer (N = 36, 51.4%). A total of 1174 BMs were treated at first treatment, corresponding to a median number of 14 BMs per patient. Most of the patients (N = 51, 72.6%) received a single fraction of 20-24 Gy. At 1 year, OS was 62.3%, with a median OS of 19.2 months, and SSR was 77.8%. A cumulative number of 1537 BM were treated over time, corresponding to a median cumulative number of 16 BM per patient. At 1-year, the LCR was 97.3%, with a cumulative incidence of radio-necrosis of 2.1% per lesion. Three patients (4.3%) presented Grade 2 toxicity, and there was no Grade ≥ 3 toxicity. The number of treated BMs and the treatment volume did not influence OS or SSR ( > 0.05).
CONCLUSIONS
SRT was highly efficient in controlling the BM, with minimal side effects. In this setting, an SRT treatment should be proposed even in patients with ≥10 BMs at diagnosis.
PubMed: 38730695
DOI: 10.3390/cancers16091742