In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or ...bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment. Thus, the switch between apoptosis and pyroptosis is also discussed. Cancer immunotherapy has gained increasing attention due to breakthroughs in immune checkpoint inhibitors; moreover, ferroptosis, necroptosis, and pyroptosis are highly correlated with the modulation of immunity in the tumor microenvironment. Compared with necroptosis and ferroptosis, pyroptosis is the primary mechanism for host defense and is crucial for bridging innate and adaptive immunity. Furthermore, recent evidence has demonstrated that pyroptosis exerts benefits on cancer immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T). Hence, in this review, we elucidate the role of pyroptosis in cancer progression and the modulation of immunity. We also summarize the potential small molecules and nanomaterials that target pyroptotic cell death mechanisms and their therapeutic effects on cancer.
The endoplasmic reticulum (ER) has diverse functions, and especially misfolded protein modification is in the focus of this review paper. With a highly regulatory mechanism, called unfolded protein ...response (UPR), it protects cells from the accumulation of misfolded proteins. Nevertheless, not only does UPR modify improper proteins, but it also degrades proteins that are unable to recover. Three pathways of UPR, namely PERK, IRE-1, and ATF6, have a significant role in regulating stress-induced physiological responses in cells. The dysregulated UPR may be involved in diseases, such as atherosclerosis, heart diseases, amyotrophic lateral sclerosis (ALS), and cancer. Here, we discuss the relation between UPR and cancer, considering several aspects including survival, dormancy, immunosuppression, angiogenesis, and metastasis of cancer cells. Although several moderate adversities can subject cancer cells to a hostile environment, UPR can ensure their survival. Excessive unfavorable conditions, such as overloading with misfolded proteins and nutrient deprivation, tend to trigger cancer cell death signaling. Regarding dormancy and immunosuppression, cancer cells can survive chemotherapies and acquire drug resistance through dormancy and immunosuppression. Cancer cells can also regulate the downstream of UPR to modulate angiogenesis and promote metastasis. In the end, regulating UPR through different molecular mechanisms may provide promising anticancer treatment options by suppressing cancer proliferation and progression.
Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein ...kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial-mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-β-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.
Purpose
This study aims to understand the underlying mechanism and boundary conditions of the IKEA effect in self-expressive mass customization (MC). It examines the effect of the extent of choice in ...MC toolkits in terms of perceived value of self-designed products, as well as how self-expression mediates this effect and what kind of consumers are more inclined to experience such effect.
Design/methodology/approach
Two experiments were conducted, using online MC toolkits. In total, 393 consumers participated in the experiments. Data collected were analyzed using t-tests, analyses of variance, path analyses, bootstrap analyses and spotlight tests.
Findings
The results show that offering a greater extent of choice in MC toolkits to consumers provides a greater opportunity for self-expression, resulting in higher product valuation. Further, consumers who have high romanticism in aesthetic preference and high self-esteem are more inclined to influences associated with this effect.
Originality/value
This research adds to the literature on the IKEA effect in self-expressive MC by identifying a key antecedent (extent of choice), its underlying mechanism (self-expression), and two boundary conditions (aesthetic preference and self-esteem). The results of this study provide firms with a better understanding of how they can improve their self-expressive MC strategies.
Over the past decades, promising therapies targeting different signaling pathways have emerged. Among these pathways, apoptosis has been well investigated and targeted to design diverse ...chemotherapies. However, some patients are chemoresistant to these therapies due to compromised apoptotic cell death. Hence, exploring alternative treatments aimed at different mechanisms of cell death seems to be a potential strategy for bypassing impaired apoptotic cell death. Emerging evidence has shown that necroptosis, a caspase-independent form of cell death with features between apoptosis and necrosis, can overcome the predicament of drug resistance. Furthermore, previous studies have also indicated that there is a close correlation between necroptosis and reactive oxygen species (ROS); both necroptosis and ROS play significant roles both under human physiological conditions such as the regulation of inflammation and in cancer biology. Several small molecules used in experiments and clinical practice eliminate cancer cells via the modulation of ROS and necroptosis. The molecular mechanisms of these promising therapies are discussed in detail in this review.
Novel ZnV2O6 ceramic was synthesized using the solid-state process. A single monoclinic crystalline phase with a space group C2/m was detected at the sintering temperatures ranging from 580 to ...670 °C. The correlations between the chemical bond parameters and microwave dielectric properties were analyzed using the P-V-L bond theory. The full width at half maximum (FWHM) of the most intense Raman peak at 914 cm–1 is inversely proportional to the Q×f value. The ZnV2O6 ceramic can be well-sintered at 640 °C to exhibit an excellent combination of microwave dielectric properties (εr =14.6, Q×f =46,000 GHz and τf =–42 ppm/°C). Additionally, the specimen sintered at 580 °C (εr =13.2, Q×f =28,000 GHz and τf =–5.2 ppm/°C) is also suggested for highly thermal-stable applications. Both samples can be used as ultra-low-temperature co-fired ceramics (ULTCCs) for high-frequency applications.
Gasdermins (GSDMs) are a protein family encoded by six paralogous genes in humans, including
GSDMA, GSDMB, GSDMC, GSDMD, GSDME
(also known as
DFNA5
), and
DFNB59
(also known as
pejvakin
). ...Structurally, members of the GSDM family possess a C-terminus (an autoinhibitory domain) and a positively charged N-terminus (a pore-forming domain) linked with divergent peptide linkers. Recently, GSDMs have been identified as key executors of pyroptosis (an immunogenic programmed cell death) due to their pore-forming activities on the plasma membrane when proteolytically cleaved by caspases or serine proteases. Accumulating studies suggest that chemoresistance is attributed to dysregulation of apoptotic machinery and that inducing pyroptosis to bypass aberrant apoptosis can potently resensitize apoptosis-resistant cancer to chemotherapeutics. Pyroptosis is initiated by pore formation and culminates with plasma membrane rupture; these processes enable the release of proinflammatory cytokines (e.g., IL-1β and IL-18) and damage-associated molecular patterns, which further modulate antitumor immunity within the tumor microenvironment. Although pyroptosis is considered a promising strategy to boost antitumor effects, it is also reported to cause unwanted tissue damage (e.g., gut damage and nephrotoxicity). Intriguingly, mounting evidence has uncovered nonpyroptotic roles of GSDMs in tumorigenesis, such as proliferation, invasion, metastasis, and drug resistance. Thus, this provides a rationale for GSDMs as potential therapeutic targets. Taken together, we shed unbiased light on the pyroptosis-dependent roles of GSDMs in cancer progression and highlighted how GSDMs modulate tumorigenesis in a pyroptosis-independent manner. It is evident that targeting GSDMs seems profound in cancer management; however, several problems require further investigation to target GSDMs from bench to bedside, which is elucidated in the discussion section.
Prolonged treatment with cisplatin (CDDP) frequently develops chemoresistance. We have previously shown that p22phox, an endoplasmic reticulum (ER) membrane protein, confers CDDP resistance by ...blocking CDDP nuclear entry in oral squamous cell carcinoma (OSCC) cells; however, the underlying mechanism remains unresolved. Using a fluorescent dye-labeled CDDP, here we show that CDDP can bind to p22phox in both cell-based and cell-free contexts. Subsequent detection of CDDP-peptide interaction by the Tris-Tricine-based electrophoresis revealed that GA-30, a synthetic peptide matching a region of the cytosolic domain of p22phox, could interact with CDDP. These results were further confirmed by liquid chromatography-mass spectrometry (LC-MS) analysis, from which MA-11, an 11-amino acid subdomain of the GA-30 domain, could largely account for the interaction. Amino acid substitutions at Cys50, Met65 and Met73, but not His72, significantly impaired the binding between CDDP and the GA-30 domain, thereby suggesting the potential CDDP-binding residues in p22phox protein. Consistently, the p22phox point mutations at Cys50, Met65 and Met73, but not His72, resensitized OSCC cells to CDDP-induced cytotoxicity and apoptosis. Finally, p22phox might have binding specificity for the platinum drugs, including CDDP, carboplatin and oxaliplatin. Together, we have not only identified p22phox as a novel CDDP-binding protein, but further highlighted the importance of such a drug-protein interaction in drug resistance.
Background and Objectives
In Taiwan, plasma use per capita ranks among the highest in the world. We aimed to describe the trends in usage after the introduction of new hospital accreditation ...standards that evaluate compliance with institutional plasma transfusion guidelines.
Materials and Methods
We identified hospitalizations receiving plasma between 2007 and 2017 from the national health insurance database. We estimated plasma transfusions per thousand capita. The risk ratio of transfusion rates among hospitalizations in 2017 compared to 2007 was estimated using logistic regression.
Results
The total number of plasma transfusions declined from 964,408 in 2007 to 659,828 in 2017, yielding a rate of 28.00 per thousand capita. The proportion of hospitalizations receiving plasma declined by 38%, from 3.89% (95% confidence interval: 3.86%–3.91%) to 2.62% (2.61%–2.64%). Gastroenterology (16.4%) and general surgery (15.3%) accounted for the largest proportions of plasma usage. Within these two services, liver diseases were the top diagnoses needing plasma use. For hospitalized patients with liver diseases, approximately 40% of plasma units were administered to patients with neither noticeable bleeding nor red blood cells transfusions. Among these patients, almost 50% received plasma with an international normalized ratio trigger of less than 1.50. The use of potential alternative therapies or anticoagulants remained quite low during this period.
Conclusion
Plasma utilization rates during hospitalizations continuously declined over 11 years. However, inappropriate plasma use remained high, while the use of alternative therapies remained low in services such as gastroenterology. To improve the appropriateness of plasma transfusions, patient blood management should be implemented in the near future.
A novel titanium(
iii
) phosphite with intriguing polymorphism and solid-state proton-coupled electron transfer (PCET) oxidation is presented. The polymorphs show structure-dependent PCET reactivity, ...interpretable by proton distribution in channels. Combined with subsequent photoreduction, the redox cycle initiated with Ti
III
can produce H
2
and transform organics.
A Ti
III
phosphite, possessing two polymorphs with different redox activities, exhibits a complete cycle of PCET reactions starting from Ti
III
to Ti
IV
via
oxidation with H
2
release, and back to Ti
III
via
photoreduction involving external e
−
/H
+
.
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