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1.
Article in English | MEDLINE | ID: mdl-38968041

ABSTRACT

BACKGROUND: Caregivers in Japan experience a high prevalence of low back pain (LBP), with age, sex, individual pain experiences, and central sensitization symptoms potentially influencing its chronic progression. OBJECTIVE: To determine the prevalence of LBP among caregivers, as well as its relation to age and sex, and explore work status, psychological factors, and central sensitization symptoms as contributing factors to chronic LBP (CLBP). METHODS: A large-scale cross-sectional survey was conducted among 1214 caregivers in 35 geriatric healthcare facilities. The survey assessed LBP and CLBP prevalence, work status, psychological factors, and central sensitization-related symptoms. Multivariate logistic regression analysis was used to identify factors influencing CLBP. RESULTS: Among 936 valid respondents, the LBP prevalence was 69.2%. No significant sex differences were found in the prevalence of LBP and CLBP. Old age, higher pain severity, and severe symptoms related to central sensitization increased the risk of CLBP. However, work status and psychological factors did not significantly contribute to CLBP. CONCLUSION: There is a high prevalence of LBP among caregivers, age and individual pain experience significantly impact CLBP. These findings emphasize the need for therapeutic strategies to manage pain intensity, especially in the acute phase, to prevent the progression to chronicity.

2.
J Cell Mol Med ; 28(13): e18509, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38957035

ABSTRACT

Pruritus is often accompanied with bacterial infections, but the underlying mechanism is not fully understood. Although previous studies revealed that lipopolysaccharides (LPS) could directly activate TRPV4 channel and TRPV4 is involved in the generation of both acute itch and chronic itch, whether and how LPS affects TRPV4-mediated itch sensation remains unclear. Here, we showed that LPS-mediated TRPV4 sensitization exacerbated GSK101-induced scratching behaviour in mice. Moreover, this effect was compromised in TLR4-knockout mice, suggesting LPS acted through a TLR4-dependent mechanism. Mechanistically, LPS enhanced GSK101-evoked calcium influx in mouse ear skin cells and HEK293T cells transfected with TRPV4. Further, LPS sensitized TRPV4 channel through the intracellular TLR4-PI3K-AKT signalling. In summary, our study found a modulatory role of LPS in TRPV4 function and highlighted the TLR4-TRPV4 interaction in itch signal amplification.


Subject(s)
Lipopolysaccharides , Phosphatidylinositol 3-Kinases , Pruritus , Signal Transduction , TRPV Cation Channels , Toll-Like Receptor 4 , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Animals , Toll-Like Receptor 4/metabolism , Pruritus/metabolism , Pruritus/chemically induced , Pruritus/pathology , Lipopolysaccharides/pharmacology , Humans , Mice , HEK293 Cells , Phosphatidylinositol 3-Kinases/metabolism , Mice, Knockout , Mice, Inbred C57BL , Male , Calcium/metabolism , Proto-Oncogene Proteins c-akt/metabolism
3.
Cureus ; 16(6): e61587, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38962595

ABSTRACT

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). Neuropathic pain in MS is a debilitating symptom that significantly impairs the quality of life for a substantial proportion of MS patients. Neuropathic pain in MS stems primarily from demyelination, axonal loss, CNS inflammation, and direct damage to the myelin sheath, leading to pain manifestations such as ongoing extremity pain, Lhermitte's phenomenon, and trigeminal neuralgia (TN). The pathophysiological mechanisms behind MS-related neuropathic pain are explored in this review, highlighting central sensitization, neural dysfunction, spinal thalamic tract dysfunction, and inflammatory processes that exacerbate neuronal damage. Neuropathic pain in MS necessitates comprehensive assessment tools and neurophysiological tests to differentiate neuropathic pain from other MS symptoms accurately. Treatment strategies for MS-related neuropathic pain encompass pharmacological interventions, including anticonvulsants and antidepressants, and emerging therapies targeting specific inflammatory processes. The review advocates for a holistic approach to management, incorporating innovative treatments and multidisciplinary strategies to address both the physical symptoms and psychosocial aspects of this disorder. This comprehensive overview underscores the importance of ongoing research into targeted therapies to improve patient outcomes and enhance the quality of life for those affected by MS.

4.
Heliyon ; 10(12): e32598, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38952362

ABSTRACT

Radiotherapy causes apoptosis mainly through direct or indirect damage to DNA via ionizing radiation, leading to DNA strand breaks. However, the efficacy of radiotherapy is attenuated in malignant tumor microenvironment (TME), such as hypoxia. Tumor vasculature, due to the imbalance of various angiogenic and anti-angiogenic factors, leads to irregular morphology of tumor neovasculature, disordered arrangement of endothelial cells, and too little peripheral coverage. This ultimately leads to a TME characterized by hypoxia, low pH and high interstitial pressure. This deleterious TME further exacerbates the adverse effects of tumor neovascularization and weakens the efficacy of conventional radiotherapy. Whereas normalization of blood vessels improves TME and thus the efficacy of radiotherapy. In addition to describing the research progress of radiotherapy sensitization and vascular normalization, this review focuses on the strategy and application prospect of modulating vascular normalization to improve the efficacy of radiotherapy sensitization.

5.
Neurosci Biobehav Rev ; 163: 105790, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38960076

ABSTRACT

Pavlovian conditioning is typically distinguished from sensitization but a Pavlovian conditional stimulus (CS) also results in sensitization. A Pavlovian CS can sensitize responding to a probe stimulus that is related to the unconditional stimulus (US) or to the US itself. Pavlovian sensitization has been studied in the defensive, sexual, and feeding systems. In Pavlovian sensitization, the focus is not on a conditional response (CR) directly elicited by the CS but on the response mode that is activated by the CS. Activation of a response mode increases the probability of particular responses and also increases reactivity to various stimuli. Pavlovian sensitization reflects this increased stimulus reactivity. Pavlovian sensitization helps uncover successful learning in situations where a conventional CR does not occur. Pavlovian sensitization also encourages broadening our conceptions of Pavlovian conditioning to include changes in afferent processes. Implications for biological fitness and for basic and translational research are discussed.

6.
Pharmacol Biochem Behav ; : 173816, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38971472

ABSTRACT

Nitric oxide (NO) is a molecule involved in plasticity across levels and systems. The role of NOergic pathways in stress-induced sensitization (SIS) of behavioral responses, in which a particular stressor triggers a state of hyper-responsiveness to other stressors after an incubation period, was assessed in adult zebrafish. In this model, adult zebrafish acutely exposed to a fear-inducing conspecific alarm substance (CAS) and left undisturbed for an incubation period show increased anxiety-like behavior 24 h after exposure. CAS increased forebrain glutamate immediately after stress and 30 min after stress, an effect that was accompanied by increased nitrite levels immediately after stress, 30 min after stress, 90 min after stress, and 24 h after stress. CAS also increased nitrite levels in the head kidney, where cortisol is produced in zebrafish. CAS-elicited nitrite responses in the forebrain 90 min (but not 30 min) after stress were prevented by a NOS-2 blocker. Blocking NOS-1 30 min after stress prevents SIS; blocking NOS-2 90 min after stress also prevents stress-induced sensitization, as does blocking calcium-activated potassium channels in this latter time window. Stress-induced sensitization is also prevented by blocking guanylate cyclase activation in both time windows, and cGMP-dependent channel activation in the second time window. These results suggest that different NO-related pathways converge at different time windows of the incubation period to induce stress-induced sensitization.

7.
Article in Chinese | MEDLINE | ID: mdl-38973033

ABSTRACT

Objective:Neosensitizations may be occur during the allergen specific immunotherapy(AIT) due to the differences between allergen vaccine's content and a patient's molecular sensitization profile. This study investigates whether AIT with HDM extract changes the sensitization profile, whether de novo sensitization occurs, and the clinical importance of the neosensitization. Methods:Fifty-three patients with HDM allergic rhinitis ,with/without asthma, patients were received one year HDM subcutaneous AIT . Fourteen patients were recruited as control group and received only necessary medications. Serum samples were collected at baseline, 6thmoths and 12thof AIT, respectively. Serum samples were tested specific IgE against Der p, Der p 1/2/3 and Der f, Der f 1/2/3, as well as IgG4 against Der p, Der p 1/2 and Der f, Der f 1/2. VAS were collected at the time-points as well. Results:In AIT group, Der p, Der p 1/3, and Der f 1/3 specific IgE levels were significantly higher after one-year treatment, especially for Der p 3. There were 69.2%(18/26) patients whose Der p 3 specific IgE below 0.35 kU/L at baseline but became positive(>0.35 kU/L) after treatment, that is, neosensitization occurred. All tested allergen specific IgG4 level significantly increased after one year AIT treatment and the VAS declined dramatically. However, for patients with neosensitization and without neosensitization, there were no significantly changes concerning to IgG4 level and VAS. Conclusion:Patients undergoing AIT might have a risk of neosensitization to the allergen components in the vaccines. However, the clinical importance of the neosensitization remains unclear and warrants further studies.


Subject(s)
Allergens , Antigens, Dermatophagoides , Desensitization, Immunologic , Immunoglobulin E , Pyroglyphidae , Humans , Immunoglobulin E/immunology , Immunoglobulin E/blood , Desensitization, Immunologic/methods , Animals , Pyroglyphidae/immunology , Allergens/immunology , Antigens, Dermatophagoides/immunology , Male , Female , Adult , Rhinitis, Allergic/immunology , Rhinitis, Allergic/therapy , Asthma/immunology , Asthma/therapy , Cysteine Endopeptidases/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology
8.
Adv Sci (Weinh) ; : e2400951, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973319

ABSTRACT

Growing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA-CaP@PD1-NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long-term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co-delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens.

9.
Article in English | MEDLINE | ID: mdl-38952261

ABSTRACT

The occurrence of cancer is often closely related to multiple tumor markers, so it is important to develop multitarget detection methods. By the proper design of the input signals and logical operations of DNA logic gates, detection and diagnosis of cancer at different stages can be achieved. For example, in the early stages, specific input signals can be designed to correspond to early specific tumor markers, thereby achieving early cancer detection. In the late stage, logic gates for multitarget detection can be designed to simultaneously detect multiple biomarkers to improve diagnostic accuracy and comprehensiveness. In this work, we constructed a dual-target-triggered DNA logic gate for anchoring DNA tetrahedra, where methylene blue was embedded in the DNA tetrahedra to sensitize ZnO@CdS@Au, achieving ultrasensitive detection of the target substance. We tested the response of AND and OR logic gates to the platform. For AND logic gates, the sensing platform only responds when both miRNAs are present. In the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. Subsequently, we used OR logic gates for miRNA detection. Even if only one target exists, the sensing platform exhibits excellent performance. Similarly, within the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. The minimum detection limit is 1.10 aM. Whether it is the need to detect multiple targets simultaneously or only one of them, we can achieve it by selecting the appropriate logic gate. This strategy holds promising application prospects in fields such as biosensing, medical diagnosis, and environmental monitoring.

10.
J Toxicol Environ Health A ; : 1-13, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967335

ABSTRACT

During the key event 1 of skin sensitization defined as covalent binding or haptenization of sensitizer to either thiol or amino group of skin proteins, a sensitizer not only covalently binds with skin proteins but also interacts with nucleophilic small molecules such as glutathione (GSH). Although GSH would not be directly associated with skin sensitization, this interaction may be applied for developing an alternative test method simulating key event 1, haptenization. Thus, the aim of the present study was to examine whether N-acetyl-L-cysteine methyl ester (NACME), a thiol-containing compound, was selected as an electron donor to determine whether NACME reacted with sensitizers. Following a reaction of NACME with a sensitizer in a 96-well plate, the remaining NACME was measured spectrophotometrically using 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB). Following the optimization of test conditions with two different vehicles, such as acetonitrile (ACN) and dimethyl sulfoxide (DMSO), 64 test chemicals were tested to determine the predictive capacity of current NACME test method. The results obtained showed, the predictive capacity of 94.6% sensitivity, 88.9% specificity, and 92.2% accuracy utilizing DMSO as a vehicle with a cutoff NACME depletion of 5.85%. The three parameters were also over 85% in case of ACN. These values were comparable to or better than other OECD-approved test methods. Data demonstrated that a simple thiol-containing compound NACME might constitute as a reliable candidate for identifying reactive skin sensitizers, and that this method be considered as practical method as a screening tool for assessing a chemical's tendency to initiate skin sensitization.

11.
Front Immunol ; 15: 1393819, 2024.
Article in English | MEDLINE | ID: mdl-38933263

ABSTRACT

Introduction & Objective: Allergic sensitization is an essential step in the development of allergic airway inflammation to birch pollen (BP); however, this process remains to be fully elucidated. Recent scientific advances have highlighted the importance of the allergen context. In this regard, microbial patterns (PAMPs) present on BP have attracted increasing interest. As these PAMPs are recognized by specialized pattern recognition receptors (PRRs), this study aims at investigating the roles of intracellular PRRs and the inflammasome regulator NLRP3. Methods: We established a physiologically relevant intranasal and adjuvant-free sensitization procedure to study BP-induced systemic and local lung inflammation. Results: Strikingly, BP-sensitized Nlrp3-deficient mice showed significantly lower IgE levels, Th2-associated cytokines, cell infiltration into the lung, mucin production and epithelial thickening than their wild-type counterparts, which appears to be independent of inflammasome formation. Intriguingly, bone-marrow chimera revealed that expression of NLRP3 in the hematopoietic system is required to trigger an allergic response. Conclusion: Overall, this study identifies NLRP3 as an important driver of BP-induced allergic immune responses.


Subject(s)
Administration, Intranasal , Allergens , Betula , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein , Pollen , Animals , Mice , Allergens/immunology , Betula/immunology , Cytokines/metabolism , Disease Models, Animal , Hypersensitivity/immunology , Immunoglobulin E/immunology , Inflammasomes/metabolism , Inflammasomes/immunology , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Plant Extracts/pharmacology , Pollen/immunology , Male , Female
12.
Biol Psychiatry ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945386

ABSTRACT

BACKGROUND: Fragile X syndrome (FXS) is a genetic condition associated with increased risk for social anxiety and avoidance. Using functional near-infrared spectroscopy (fNIRS), we previously demonstrated aberrant neural activity responding to faces in young girls with FXS cross-sectionally. Here, we tested the hypothesis that abnormalities in neural activation and sensitization would increase with age in 65 girls with FXS, ages 5-16 years, relative to an age-matched control group of 52 girls who had comparable cognitive function and clinical symptoms. METHODS: Functional NIRS data were collected at two time points, 2.8±0.6 years apart during a face-processing task. Linear mixed-effects models examined longitudinal neural profiles in girls with FXS and control. Correlational analysis was performed to examine associations between neural sensitization (increasing neural response to repeated stimuli), and clinical ratings. RESULTS: In girls with FXS, 32 participants had one, and 24 had two fNIRS scans. In controls, 21 had one, and 29 had two fNIRS scans. Brain activations in the right middle and superior frontal gyri were higher in FXS than controls at both time points. Neural sensitization also increased in FXS at a higher rate than controls in the superior frontal gyrus when responding to upright faces. For the FXS group, sensitization in the superior frontal gyrus positively correlated with longitudinal increases in anxiety and social avoidance scores. CONCLUSION: Girls with FXS show increasingly abnormal neural activation and sensitization responding to faces over time. Aberrant neural sensitization in girls with FXS is associated with longitudinal changes in anxiety and social skills.

13.
Addict Neurosci ; 112024 Jun.
Article in English | MEDLINE | ID: mdl-38938269

ABSTRACT

Low sensitivity (LS) to alcohol is a risk factor for alcohol use disorder (AUD). Compared to peers with high sensitivity (HS), LS individuals drink more, report more problems, and exhibit potentiated alcohol cue reactivity (ACR). Heightened ACR suggests LS confers AUD risk via incentive sensitization, which is thought to take place in the mesocorticolimbic system. This study examined neural ACR in LS and HS individuals. Young adults (N = 32, M age=20.3) were recruited based on the Alcohol Sensitivity Questionnaire (HS: n = 16; LS: n = 16; 9 females/group). Participants completed an event-related fMRI ACR task. Group LS had higher ACR in left ventrolateral prefrontal cortex than group HS. In group LS, ACR in left caudomedial orbitofrontal cortex or left putamen was low at low alcohol use levels and high at heavier or more problematic alcohol use levels, whereas the opposite was true in group HS. Alcohol use level also was associated with the level of ACR in left substantia nigra among males in group LS. Taken together, results suggest elevated mesocorticolimbic ACR among LS individuals, especially those using alcohol at hazardous levels. Future studies with larger samples are warranted to determine the neurobiological loci underlying LS-based amplified ACR and AUD risk.

14.
Antioxidants (Basel) ; 13(6)2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38929165

ABSTRACT

Chronic migraine is a disabling disorder without effective therapeutic medicine. AMPA receptors have been proven to be essential to pathological pain and headaches, but the related regulatory mechanisms in chronic migraine have not yet been explored. In this study, we found that the level of surface GluA2 was reduced in chronic migraine rats. Tat-GluR23Y (a GluA2 endocytosis inhibitor) reduced calcium inward flow and weakened synaptic structures, thus alleviating migraine-like pain sensitization. In addition, the inhibition of GluA2 endocytosis reduced the calcium influx and alleviated mitochondrial calcium overload and ROS generation in primary neurons. Furthermore, our results showed that ROS can induce allodynia and GluA2 endocytosis in rats, thus promoting migraine-like pain sensitization. In our previous study, the dopamine D2 receptor was identified as a potential target in the treatment of chronic migraine, and here we found that dopamine D2 receptor activation suppressed chronic-migraine-related pain sensitization through blocking the GluA2/ROS positive feedback loop in vivo and in vitro. Additionally, ligustrazine, a core component of ligusticum chuanxiong, was shown to target the dopamine D2 receptor, thereby alleviating ROS production and abnormal nociception in CM rats. This study provides valuable insight into the treatment of chronic migraine.

15.
Medicina (Kaunas) ; 60(6)2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38929571

ABSTRACT

Cannabis allergy is a relatively new phenomenon described in the 1970s. Its increased frequency has been observed over the last years due to the increasing therapeutic and recreational use of cannabis-based products. Sensitization possibly leading to allergy symptoms can occur not only through the smoking of cannabis, but also through ingestion, the inhalation of pollen, or direct contact. The severity of symptoms varies from benign pruritus to anaphylaxis. There is scant information available to support clinicians throughout the entire therapeutic process, starting from diagnosis and ending in treatment. In this review, we present six cases of patients in whom molecular in vitro testing revealed sensitization to cannabis extract and/or cannabis-derived nsLTP molecules (Can s 3). Based on these cases, we raise important questions regarding this topic. The article discusses current proposals and highlights the importance of further research not only on cannabis allergy but also on asymptomatic sensitization to cannabis allergens, which may be ascertained in some percentage of the population.


Subject(s)
Allergens , Cannabis , Immunoglobulin E , Humans , Allergens/immunology , Allergens/adverse effects , Cannabis/adverse effects , Hypersensitivity/immunology , Hypersensitivity/diagnosis , Immunoglobulin E/blood , Immunoglobulin E/immunology
16.
Life (Basel) ; 14(6)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38929706

ABSTRACT

Methamphetamine (METH) exposure increases locomotor sensitization. However, no study has explored the occurrence of cardiovascular sensitization. The present study, carried out in mice, analyzed the following: (i) METH sensitization extending to systolic blood pressure (SBP); (ii) a potential correlation between ambulatory and cardiovascular sensitization; and (iii) morphological alterations within meso-striatal, meso-limbic and pontine catecholamine systems including c-fos expression. Locomotor activity, SBP and occurrence of morphological alterations of catecholaminergic neurons were assessed in C57Bl/6J mice following daily i.p. injections of either saline or METH (1, 2 or 5 mg/kg) for 5 consecutive days and following 6 days of withdrawal. Reiterated exposure to the lower doses of METH (1 mg/kg and 2 mg/kg) produced in mice locomotor sensitization without altering SBP. In contrast, repeated treatment with the highest dose of METH (5 mg/kg) produced sensitization of SBP in the absence of locomotor sensitization. No morphological alterations but increases in c-fos expression within neurons of locus coeruleus and nucleus accumbens were detected. The present data suggest that METH produces plastic changes that extend beyond the motor systems to alter autonomic regulation. This cardiovascular sensitization occurs independently of locomotor sensitization. The persistency of increased blood pressure may underlie specific mechanisms operating in producing hypertension.

17.
Chem Asian J ; : e202400697, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38941239

ABSTRACT

Novel D-A1-A2-π-A organic sensitizers (FZ-sensitizer), utilizing spiro[fluorene-9,9'-phenanthren]-10'-one (A1) and benzo[c][1,2,5]thiadiazole(A2) moiety as two auxiliary acceptors, are synthesized and applied in dye-sensitized solar cells (DSSCs) and hydrogen production. By incorporating a bulky A1 and A2 between the donor (D) and π-bridge moiety, structural modifications inhibit molecular aggregation, while the carbonyl group enhances the capture of Li+ ions, thereby delaying charge recombination. Furthermore, the extended π-conjugation broadens the light absorption range and enhances the power conversion efficiency (PCE) of FZ-2 under AM1.5 conditions, achieving up to 5.72%. Co-sensitization with N719 and FZ-2 shows PCE of 9.60% under one sun. Under TL84 indoor light conditions, the efficiency is 29.69% at 2500 lux. FZ-sensitizers also exhibit high efficiency in photocatalytic hydrogen production. The hydrogen production activities of FZ-2 are 9190 µmol/g (1 hour) and 76582 µmol/g (12 hours) respectively, while those of FZ-1 are 7430 µmol/g (1 hour) and 64004 µmol/g (12 hours), indicating that FZ-2 can inject charges into TiO2 more efficiently and utilize them for water splitting. Stability testing of photocatalytic water splitting after 12 hours shows a turnover number (TON) of 4249 for FZ-1 and 5378 for FZ-2.

18.
Mol Pharm ; 21(7): 3218-3232, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38885477

ABSTRACT

Squamous cell carcinoma (SCC) is a common nonmelanoma skin cancer. Radiotherapy plays an integral role in treating SCC due to its characteristics, such as diminished intercellular adhesion, heightened cell migration and invasion capabilities, and immune evasion. These problems lead to inaccurate tumor boundary positioning and radiotherapy tolerance in SCC treatment. Thus, accurate localization and enhanced radiotherapy sensitivity are imperative for effective SCC treatment. To address the existing limitations in SCC therapy, we developed monoglyceride solid lipid nanoparticles (MG SLNs) and enveloped them with the A431 cell membrane (A431 CM) to create A431@MG. The characterization results showed that A431@MG was spherical. Furthermore, A431@MG had specific targeting for A431 cells. In A431 tumor-bearing mice, A431@MG demonstrated prolonged accumulation within tumors, ensuring precise boundary localization of SCC. We further advanced the approach by preparing MG SLNs encapsulating 5-aminolevulinic acid methyl ester (MLA) and desferrioxamine (DFO) with an A431 CM coating to yield A431@MG-MLA/DFO. Several studies have revealed that DFO effectively reduced iron content, impeding protoporphyrin IX (PpIX) biotransformation and promoting PpIX accumulation. Simultaneously, MLA was metabolized into PpIX upon cellular entry. During radiotherapy, the heightened PpIX levels enhanced reactive oxygen species (ROS) generation, inducing DNA and mitochondrial damage and leading to cell apoptosis. In A431 tumor-bearing mice, the A431@MG-MLA/DFO group exhibited notable radiotherapy sensitization, displaying superior tumor growth inhibition. Combining A431@MG-MLA/DFO with radiotherapy significantly improved anticancer efficacy, highlighting its potential to serve as an integrated diagnostic and therapeutic strategy for SCC.


Subject(s)
Carcinoma, Squamous Cell , Cell Membrane , Nanoparticles , Radiation-Sensitizing Agents , Skin Neoplasms , Animals , Mice , Nanoparticles/chemistry , Humans , Cell Line, Tumor , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Radiation-Sensitizing Agents/chemistry , Radiation-Sensitizing Agents/pharmacology , Radiation-Sensitizing Agents/administration & dosage , Cell Membrane/metabolism , Aminolevulinic Acid/chemistry , Aminolevulinic Acid/pharmacology , Aminolevulinic Acid/administration & dosage , Lipids/chemistry , Xenograft Model Antitumor Assays , Deferoxamine/chemistry , Deferoxamine/pharmacology , Mice, Nude , Female , Mice, Inbred BALB C , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , Liposomes
19.
Article in English | MEDLINE | ID: mdl-38913398

ABSTRACT

Summary: Background. Grass and olive pollens have overlapping pollination periods and are common allergens in the Iberian Peninsula. The objective is to determine the sensitization pattern to major Phleum pratense and Olea europaea pollens in the Portuguese population with pollen allergic rhinitis (AR) using molecular allergen diagnosis (MAD). Methods. Seasonal AR patients (≥ 12 years), with positive skin prick tests (SPT) to Phleum and Olea were recruited from 16 centers. Using ALEX2, specific IgE to Phl p1, Phl p2, Phl p5, Phl p6, Phl p7, Phl p 12, Ole e1, Ole e7 and Ole e9 were determined. Immunoblotting of Olea allergic patients was performed. Results. Included 175 patients (55.4% female; mean age 31.6 ± 13.3 years; 85.7% adults; 40% asthmatic, Coast 28%/Inland 72% and North 29.1%/Centre 20.6%/South 50.3%). Considering Phleum MAD, 85.7% were sensitized to Phl p1, 45.7% to Phl p2, 50.3% to Phl p5, 45.7%, to Phl p6, 10.9% to Phl p7 and 22.9% to Phl p12. Sensitization to Ole e1 was found in 56.6%, to Ole e7 in 1.7% and Ole e9 in 3.4% patients. Sensitization to Phl p7 was more frequent in asthmatics (17.4% vs 6.6%; p = 0.044). Sensitization to Phl p5, Phl p6, Phl p12 and Ole e1 was more frequent in inland. Regarding sensitization patterns: 53.1% patients were sensitized to both species genuine´ sIgE, 38.3% to Phleum and 3.4% only to Olea species' sIgE. Immunoblotting of Olea allergic patients showed a high intensity band that may correspond to Ole e12. Conclusions. MAD showed "genuine" Grass and Olea sensitization in approximately 50% of our patients.

20.
Behav Processes ; 220: 105060, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909665

ABSTRACT

In many biparental mammals, such as California mice (Peromyscus californicus), fathers display affiliative behavior toward unfamiliar infants whereas reproductively naïve adult males show highly variable responses. Sources of this variability are not well understood, but evidence suggests that stress can either enhance or inhibit alloparental care. We evaluated immediate and delayed effects of acute stress on pup-directed behavior in adult virgin male California mice. Mice underwent three 10-minute tests with unfamiliar pups at 48-hour intervals. Stressed mice (N=22) received a subcutaneous oil injection immediately before tests 1 and 2, whereas controls (N=22) were left undisturbed. In controls, but not stressed mice, latency to approach the pup decreased and duration of alloparental behavior increased across the three tests. At each time point, stressed males were less likely than controls to perform alloparental behavior. Controls spent significantly more time performing alloparental behavior than stressed mice in tests 1 and 2 but not in test 3. Pup-directed aggression did not differ between the groups at any time point. These findings suggest that acute stress can both inhibit alloparental behavior in the short term and prevent the increase in alloparental behavior that typically occurs with repeated exposure to pups in virgin male California mice.

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