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Asian Pacific Journal of Cancer... Jun 2024This study aimed to discover the cytotoxic effect of YH239-EE and YH239 alone and their enantiomer potency in cytotoxic effect on the MCF7 cell line.
OBJECTIVE
This study aimed to discover the cytotoxic effect of YH239-EE and YH239 alone and their enantiomer potency in cytotoxic effect on the MCF7 cell line.
METHODS
We used the cytotoxic study on MDM2 cell lines by detecting the percentage of apoptosis and necrosis by annexin v methods.
RESULT
This result shows that YH239-EE causes more apoptosis and necrosis 40% in comparison to YH239 without ethyl ester, about 4.92 %, and The (+) enantiomer of YH239-EE demonstrated a markedly higher induction of apoptosis and necrosis (84.48%) in MCF7 cells compared to the (-) enantiomer (48.71%).
CONCLUSION
The ethyl ester group in YH239-EE might play a crucial role in enhancing the compound's ability to induce cell death, and The high efficacy of the (+) enantiomer of YH239-EE in inducing cell death in MCF7 cells suggests it may be a more promising therapeutic candidate for breast cancer treatment, specifically for subtypes represented by MCF7 cells.
Topics: Humans; Apoptosis; Breast Neoplasms; MCF-7 Cells; Female; Cell Proliferation; Tumor Cells, Cultured; Antineoplastic Agents; Stereoisomerism
PubMed: 38918676
DOI: 10.31557/APJCP.2024.25.6.2133 -
Asian Pacific Journal of Cancer... Jun 2024The miR-451 has been reported to play an important role in colorectal cancer (CRC) pathogenesis and can be a pivotal diagnosis biomarker of CRC. Given the contradictions... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The miR-451 has been reported to play an important role in colorectal cancer (CRC) pathogenesis and can be a pivotal diagnosis biomarker of CRC. Given the contradictions in the diagnosis value of the miR-451 in patients with CRC, deciphering the diagnostic/prognostic role of this miRNA in CRC will support the identification of a novel therapeutic target for CRC. Therefore, in the present meta-analysis, we evaluated the diagnostic value of miR-451 in CRC patients.
MATERIALS AND METHODS
The electronic databases of Embase, PubMed, ISI Web of Science, and Scopus systematically searched for relevant studies. The odds ratio (OR) with a 95% confidence interval (CI) was calculated to evaluate the association between miR-451 family expression and diagnosis of colorectal cancer. The parameters including sensitivity, specificity, and area under the curve (AUC) were obtained. The quality of evidence was evaluated using the Newcastle-Ottava Scale (NOS).
RESULTS
This study involved 510 patients (45% female and 55% male) with CRC. The pooled analysis of the studies showed a significant association between low expression levels of miR-451 in patients with CRC (OR = 7.59; 95% CI 2.39 - 24.07; p = 0.001). The overall sensitivity and specificity were 0.95 (0.61 - 1) and 0.83 (0.43 - 0.99), respectively. The pooled AUC was 0.97 (0.88 - 1; p < 0.006). Results showed if the pre-test probability is 50% for a patient, the post-test probability will be 85%. The indices demonstrated the high potency of miR-451 as a diagnostic biomarker in patients with CRC. No publication bias was observed using the Begg's (p=0.85) and Egger's tests (p=0.45).
CONCLUSION
A strong relationship between the low expression levels of miR-451 and CRC progression was observed. This finding suggests the miR-451 family may be helpful as a potential biomarker for the earlier diagnosis of colorectal cancer.
Topics: Humans; Colorectal Neoplasms; MicroRNAs; Prognosis; Biomarkers, Tumor; Female
PubMed: 38918650
DOI: 10.31557/APJCP.2024.25.6.1903 -
Cureus May 2024Supraspinatus tears are a common injury, particularly among athletes who engage in sports that include repetitive overhead motions, such as baseball players. Standard...
Supraspinatus tears are a common injury, particularly among athletes who engage in sports that include repetitive overhead motions, such as baseball players. Standard conservative therapies include rest and activity modification, physical therapy, non-steroidal anti-inflammatory drugs (NSAIDs), cold/heat therapy, and corticosteroid injections. Ongoing research and anecdotal evidence support using platelet-rich plasma (PRP) for supraspinatus/rotator cuff tears. Platelet releasate is obtained from PRP via the activation of platelets, subsequently releasing bioactive substances. Activation can be achieved through various methods, some of which include the addition of calcium chloride, thrombin, or exposure to low-level lasers. Platelet releasate has the potential to assist in the healing of tears by releasing growth factors that facilitate muscle and tendon repair. This case presentation discusses the outcomes of platelet releasate paired with extracorporeal shock wave therapy (ESWT) for the treatment of a partial-thickness supraspinatus tear in an 18-year-old male baseball athlete. After exploring conservative treatment options, the patient opted for a single platelet releasate injection along with a four-part series with ESWT. Four weeks post-procedure, the patient reported a 25% improvement. He was able to fully return to play for the entire baseball season. Although the effectiveness of platelet releasate is still a topic of debate and further investigation, this case demonstrates how platelet releasate shows promising results in accelerating the treatment recovery for a partial supraspinatus tear. Further investigation and research could support the benefit of this procedure for accelerated recovery of injuries compared to PRP.
PubMed: 38915987
DOI: 10.7759/cureus.61057 -
Frontiers in Endocrinology 2024Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis...
PURPOSE
Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis and epidemiology of diseases, as well as to discover new therapeutic targets. Therefore, based on systematic "druggable" genomics, we aim to identify new therapeutic targets for diabetes and analyze its pathophysiological mechanisms to promote its new therapeutic strategies.
MATERIAL AND METHOD
We used double sample MR to integrate the identified druggable genomics to evaluate the causal effect of quantitative trait loci (eQTLs) expressed by druggable genes in blood on type 1 and 2 diabetes (T1DM and T2DM). Repeat the study using different data sources on diabetes and its complications to verify the identified genes. Not only that, we also use Bayesian co-localization analysis to evaluate the posterior probabilities of different causal variations, shared causal variations, and co-localization probabilities to examine the possibility of genetic confounding. Finally, using diabetes markers with available genome-wide association studies data, we evaluated the causal relationship between established diabetes markers to explore possible mechanisms.
RESULT
Overall, a total of 4,477 unique druggable genes have been gathered. After filtering using methods such as Bonferroni significance (P<1.90e-05), the MR Steiger directionality test, Bayesian co-localization analysis, and validation with different datasets, Finally, 7 potential druggable genes that may affect the results of T1DM and 7 potential druggable genes that may affect the results of T2DM were identified. Reverse MR suggests that C4B may play a bidirectional role in the pathogenesis of T1DM, and none of the other 13 target genes have a reverse causal relationship. And the 7 target genes in T2DM may each affect the biomarkers of T2DM to mediate the pathogenesis of T2DM.
CONCLUSION
This study provides genetic evidence supporting the potential therapeutic benefits of targeting seven druggable genes, namely MAP3K13, KCNJ11, REG4, KIF11, CCNE2, PEAK1, and NRBP1, for T2DM treatment. Similarly, targeting seven druggable genes, namely ERBB3, C4B, CD69, PTPN22, IL27, ATP2A1, and LT-β, has The potential therapeutic benefits of T1DM treatment. This will provide new ideas for the treatment of diabetes and also help to determine the priority of drug development for diabetes.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Diabetes Mellitus, Type 2; Quantitative Trait Loci; Genetic Predisposition to Disease; Bayes Theorem; Diabetes Mellitus, Type 1; Genomics; Hypoglycemic Agents; Polymorphism, Single Nucleotide
PubMed: 38915894
DOI: 10.3389/fendo.2024.1366290 -
Oncoimmunology 2024Regulatory T cells (Tregs) play a crucial role in mediating immunosuppression in the tumor microenvironment. Furthermore, Tregs contribute to the lack of efficacy and...
Regulatory T cells (Tregs) play a crucial role in mediating immunosuppression in the tumor microenvironment. Furthermore, Tregs contribute to the lack of efficacy and hyperprogressive disease upon Programmed cell death protein 1 (PD-1) blockade immunotherapy. Thus, Tregs are considered a promising therapeutic target, especially when combined with PD-1 blockade. However, systemic depletion of Tregs causes severe autoimmune adverse events, which poses a serious challenge to Treg-directed therapy. Here, we developed a novel treatment to locally and predominantly damage Tregs by near-infrared duocarmycin photorelease (NIR-DPR). In this technology, we prepared anti-CD25 F(ab') conjugates, which site-specifically uncage duocarmycin in CD25-expressing cells upon exposure to NIR light. , CD25-targeted NIR-DPR significantly increased apoptosis of CD25-expressing HT2-A5E cells. When tumors were irradiated with NIR light , intratumoral CD25 Treg populations decreased and Ki-67 and Interleukin-10 expression was suppressed, indicating impaired functioning of intratumoral CD25 Tregs. CD25-targeted NIR-DPR suppressed tumor growth and improved survival in syngeneic murine tumor models. Of note, CD25-targeted NIR-DPR synergistically enhanced the efficacy of PD-1 blockade, especially in tumors with higher CD8/Treg PD-1 ratios. Furthermore, the combination therapy induced significant anti-cancer immunity including maturation of dendritic cells, extensive intratumoral infiltration of cytotoxic CD8 T cells, and increased differentiation into CD8 memory T cells. Altogether, CD25-targeted NIR-DPR locally and predominantly targets Tregs in the tumor microenvironment and synergistically improves the efficacy of PD-1 blockade, suggesting that this combination therapy can be a rational anti-cancer combination immunotherapy.
Topics: Animals; T-Lymphocytes, Regulatory; Mice; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Duocarmycins; Immunoconjugates; Humans; Cell Line, Tumor; Female; Interleukin-2 Receptor alpha Subunit; Immune Checkpoint Inhibitors; Disease Models, Animal; Mice, Inbred C57BL; Apoptosis; Infrared Rays
PubMed: 38915782
DOI: 10.1080/2162402X.2024.2370544 -
Frontiers in Immunology 2024Metal ions play an essential role in regulating the functions of immune cells by transmitting intracellular and extracellular signals in tumor microenvironment (TME).... (Review)
Review
Metal ions play an essential role in regulating the functions of immune cells by transmitting intracellular and extracellular signals in tumor microenvironment (TME). Among these immune cells, we focused on the impact of metal ions on T cells because they can recognize and kill cancer cells and play an important role in immune-based cancer treatment. Metal ions are often used in nanomedicines for tumor immunotherapy. In this review, we discuss seven metal ions related to anti-tumor immunity, elucidate their roles in immunotherapy, and provide novel insights into tumor immunotherapy and clinical applications.
Topics: Tumor Microenvironment; Humans; Neoplasms; Metals; Animals; Immunotherapy; Ions; T-Lymphocytes
PubMed: 38915413
DOI: 10.3389/fimmu.2024.1379365 -
Frontiers in Immunology 2024With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in...
With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency.
Topics: Humans; Female; Aged; Adrenal Insufficiency; Immune Checkpoint Inhibitors; Addison Disease; Hydrocortisone
PubMed: 38915406
DOI: 10.3389/fimmu.2024.1371527 -
Frontiers in Immunology 2024Garlic ( L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to... (Review)
Review
Garlic ( L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many and studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, β-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and β-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.
Topics: Garlic; Humans; Animals; Plant Extracts; Antioxidants; Phytochemicals; Sulfinic Acids; Disulfides
PubMed: 38915405
DOI: 10.3389/fimmu.2024.1277074 -
RSC Advances Jun 2024Photodynamic therapy (PDT) is an alternative, minimally invasive treatment for human diseases such as cancer. PDT uses a photosensitizer to transfer photon energy...
Photodynamic therapy (PDT) is an alternative, minimally invasive treatment for human diseases such as cancer. PDT uses a photosensitizer to transfer photon energy directly to cellular O to generate O (Type II), the toxicity of which leads to cancer cell death. In this work, the photoluminescence mechanisms of a BF-formazanate dye sensitizer (BF-FORM) and its iodinated derivative (BF-FORM-D) were studied using complementary theoretical approaches; the photoluminescence pathways in the S and T states were studied using density functional theory (DFT) and time-dependent (TD)-DFT methods, the kinetic and thermodynamic properties of the pathways using the transition state theory (TST), and the time evolution and dynamics of key processes using non-adiabatic microcanonical molecular dynamics simulations with surface-hopping dynamics (NVE-MDSH). Evaluation of the potential energy surfaces (PESs) in terms of the rotations of the phenyl rings suggested a pathway for the S → S transition for the perpendicular structure, whereas two pathways were anticipated for the T → S transition, namely, [T → S] occurring immediately after the S/T intersystem crossing (ISC) and [T → S] occurring after the S/T ISC and T equilibrium structure relaxation, with the T → S energy gap being comparable to the energy required for O → O. The PESs also showed that because of the heavy-atom effect, BF-FORM-D possessed a significantly smaller S/T energy gap than BF-FORM. The TST results revealed that at room temperature, BF-FORM-D was thermodynamically more favorable than the parent molecule. Analysis of the NVE-MDSH results suggested that the librational motions of the phenyl rings play an important role in the internal conversion (IC) and ISC, and the S/T ISC and T → S transitions could be enhanced by varying the irradiation wavelength and controlling the temperature. These findings can be used as guidelines to improve and/or design photosensitizers for PDT.
PubMed: 38915335
DOI: 10.1039/d4ra02240h -
Journal of Anesthesia, Analgesia and... Jun 2024Noninvasive ventilation (NIV) is widely employed as the initial treatment for patients with chronic acute exacerbation of obstructive pulmonary disease (AECOPD)....
Effect of high-flow nasal cannula at different flow rates on diaphragmatic function in subjects recovering from an acute exacerbation of COPD: a physiological prospective pilot study.
BACKGROUND
Noninvasive ventilation (NIV) is widely employed as the initial treatment for patients with chronic acute exacerbation of obstructive pulmonary disease (AECOPD). Nevertheless, high-flow nasal cannula (HFNC) has been increasingly utilized and investigated to mitigate the issues associated with NIV. Flow rate may play a significant role in diaphragmatic function among subjects recovering from AECOPD. Based on these observations, we conducted a physiological study to assess the impact of HFNC therapy on diaphragmatic function, as measured by US, respiratory rate (RR), gas exchange, and patient comfort at various flow rates.
METHODS
A prospective physiological pilot study enrolled subjects with a diagnosis of AECOPD who required NIV for more than 24 h. After stabilization, these subjects underwent a 30-min trial using NIV and HFNC at different sequential flow rates (30-60 L/min). At the end of each trial, diaphragmatic displacement (DD, cm) and diaphragmatic thickness fraction (DTF, %) were measured using ultrasound. Additionally, other physiological variables, such as RR, gas exchange, and patient comfort, were recorded.
RESULTS
A total of 20 patients were included in the study. DD was no different among trials (p = 0.753). DTF (%) was significantly lower with HFNC-30 L/min compared to HFNC-50 and 60 L/min (p < 0.001 for all comparisons). No significant differences were found in arterial pH and PCO at discontinuation of NIV and at the end of HFNC trials (p > 0.050). During HFNC trials, RR remained unchanged without statistically significant differences (p = 0.611). However, we observed that HFNC improved comfort compared to NIV (p < 0.001 for all comparisons). Interestingly, HFNC at 30 and 40 L/min showed greater comfort during trials.
CONCLUSIONS
In subjects recovering from AECOPD and receiving HFNC, flows above 40 L/min may not offer additional benefits in terms of comfort and decreased respiratory effort. HFNC could be a suitable alternative to COT during breaks off NIV.
PubMed: 38915126
DOI: 10.1186/s44158-024-00173-3