Metallophthalocyanine as ideal antibiotics without light: Mechanisms and applications.

The urgent global health problem of antimicrobial resistance (AMR) calls for the discovery of new antibiotics with innovative modes of action while considering the low toxicity to mammalian cells. This paper proposes a novel strategy for designing antibiotics with selective bacterial toxicity by exploiting the positional differences of electron transport chains (ETC) in bacterial and mammalian cells. The focus is on cytochrome c (cyt C) and its maturation system in E. coli. The catalytic oxidative activity of metallophthalocyanine (MPc), which have a distinctive M-N4 structure, is being investigated. Unlike previous applications based on light-activated reactive oxygen species (ROS) generation, this study exploits the ability of MPcs to oxidize Fe2+ to Fe3+ in cyt C and catalyze the formation of disulfide bonds between cysteine residues to interfere with cyt C maturation, disrupt the bacterial respiratory chain and selectively kills bacteria. In contrast, in mammalian cells, these MPcs are located in the lysosomes and cannot access the ETC in the mitochondria, thus achieving selective bacterial toxicity. Two MPcs that showed effective antibacterial activity in a wound infection model were identified. This study provides a valuable reference for the design of novel antibiotics based on M-N4-based metal complex molecules.

A novel photo-enzyme platform based on non-metallic modified carbon nitride for removal of bisphenol A in water.

A nonmetallic composite photocatalyst with 2D/2D structure was prepared by hydrothermal in-situ polymerization and used for the immobilization of cytochrome C (Cyt c). The photo-enzyme coupling system has a very high enzyme load, which can reach 528.29 mg g-1 after optimization. Compared with free Cyt c, Cytc/PEDOT/CN showed better enzymatic activity, stability and catalytic efficiency. Even after being stored at 100 °C for 60 min, the enzyme activity remained at 49.42 % and remained at 57.89 % after 8 cycles. Moreover, Cytc0.5/PEDOT3/CN showed excellent photocatalytic degradation performance in the degradation experiment of bisphenol A (BPA), reaching 68.22 % degradation rate within 60 min, which was 3.9 times higher than that of pure g-C3N4 and 1.61 times higher than that of pure PEDOT3/CN. This study shows that the introduction of conductive polymers is of great significance to the photo-enzyme coupling system and provides a new strategy for the treatment of phenol-containing wastewater.

pH-Stimulated Response Gating for Mimic Cytochrome C Transport on Biomimetic Asymmetric Nanochannels.

Proteins are vital components in cells, biological tissues, and organs, playing a pivotal role in growth and developmental processes in living organisms. Cytochrome C (Cyt C) is a class of heme proteins found in almost all life and is involved in cellular energy metabolic processes such as respiration, mainly as electron carriers or terminal reductases. It binds cardiolipin in the inner mitochondrial membrane, leading to apoptosis. It is a challenge to design a simple and effective artificial system to mimic the complex Cyt C biological transport process. In this paper, an asymmetric biomimetic pH-driven protein gate is described by introducing arginine (Arg) at one end of an hourglass-shaped nanochannel. The nanochannel shows a sensitive protonation-driven protein gate that can be "off" at pH = 7 and "on" at pH = 2. Further studies show that differences in the binding of Arg and Cyt C at different levels of protonation lead to different switching behaviors within the nanochannels, which in turn lead to different surface charges within the nanochannels. It can be used for detecting Cyt C and as an excellent and robust gate for developing integrated circuits and nanoelectronic logic devices.

The appearance of cytoplasmic cytochrome C precedes apoptosis during Drosophila salivary gland degradation.

Apoptosis is an important process for organism development that functions to eliminate cell damage, maintain homeostasis, and remove obsolete tissues during morphogenesis. In mammals, apoptosis is accompanied by the release of cytochrome C (Cyt-c) from mitochondria to the cytoplasm. However, whether this process is conserved in the fruit fly, Drosophila melanogaster, remains controversial. In this study, we discovered that during the degradation of Drosophila salivary gland, the transcription of mitochondria apoptosis factors (MAPFs), Cyt-c, and death-associated APAF1-related killer (Dark) encoding genes are all upregulated antecedent to initiator and effector caspases encoding genes. The proteins Cyt-c and the active caspase 3 appear gradually in the cytoplasm during salivary gland degradation. Meanwhile, the Cyt-c protein colocates with mito-GFP, the marker indicating cytoplasmic mitochondria, and the change in mitochondrial membrane potential coincides with the appearance of Cyt-c in the cytoplasm. Moreover, impeding or promoting 20E-induced transcription factor E93 suppresses or enhances the staining of Cyt-c and the active caspase 3 in the cytoplasm of salivary gland, and accordingly decreases or increases the mitochondrial membrane potential, respectively. Our research provides evidence that cytoplasmic Cyt-c appears before apoptosis during Drosophila salivary gland degradation, shedding light on partial conserved mechanism in apoptosis between insects and mammals.

PGAM5 exacerbates acute renal injury by initiating mitochondria-dependent apoptosis by facilitating mitochondrial cytochrome c release.

Acute kidney injury (AKI) is a worldwide public health problem characterized by the massive loss of tubular cells. However, the precise mechanism for initiating tubular cell death has not been fully elucidated. Here, we reported that phosphoglycerate mutase 5 (PGAM5) was upregulated in renal tubular epithelial cells during ischaemia/reperfusion or cisplatin-induced AKI in mice. PGAM5 knockout significantly alleviated the activation of the mitochondria-dependent apoptosis pathway and tubular apoptosis. Apoptosis inhibitors alleviated the activation of the mitochondria-dependent apoptosis pathway. Mechanistically, as a protein phosphatase, PGAM5 could dephosphorylate Bax and facilitate Bax translocation to the mitochondrial membrane. The translocation of Bax to mitochondria increased membrane permeability, decreased mitochondrial membrane potential and facilitated the release of mitochondrial cytochrome c (Cyt c) into the cytoplasm. Knockdown of Bax attenuated PGAM5 overexpression-induced Cyt c release and tubular cell apoptosis. Our results demonstrated that the increase in PGAM5-mediated Bax dephosphorylation and mitochondrial translocation was implicated in the development of AKI by initiating mitochondrial Cyt c release and activating the mitochondria-dependent apoptosis pathway. Targeting this axis might be beneficial for alleviating AKI.

Exploring the induction of endometrial epithelial cell apoptosis in clinical-type endometritis in yaks through the cyt-c/caspase-3 signaling axis.

Endometritis is a significant contributor to reduced productivity in yaks in Tibet, China. The Cyt-c/Caspase-3 signaling axis plays a crucial role in the mitochondrial pathway that triggers cell apoptosis due to endogenous factors. In this study, we examined the endometrial epithelial tissue of yaks with endometritis using pathological examination, immunohistochemical analysis, TUNEL staining, qRT-PCR, and Western blot. The results indicated significant changes in the apoptotic factors of the Cyt-c/Caspase-3 signaling axis. The expression levels of Bak1, Bax, Cyt-c, Apaf-1, Caspase-9, and Caspase-3 were significantly increased (P < 0.05), while the expression level of Bcl-2 was significantly decreased. Immunohistochemistry results revealed significant increase in Bak1, Bax, Cyt-c, Apaf-1, Caspase-9, and Caspase-3 expression in the cytoplasm compared to the healthy group, except for Bcl-2, which showed a significant decrease. Pathological section analysis demonstrated that clinical endometritis in yaks led to structural damage, bleeding, congestion, and inflammatory cell infiltration in the endometrial epithelium. Our study findings indicated that clinical endometritis in yaks can modulate apoptosis of endometrial epithelial cells via the Cyt-c/Caspase-3 signaling pathway, resulting in different levels of damage. This research is pioneering in exploring cell apoptosis induced by clinical endometritis in yaks, offering novel insights and potential strategies for the future prevention and treatment of endometritis in yaks.

Inter-domain interaction of ferredoxin-NADP+ reductase important for the negative cooperativity by ferredoxin and NADP(H).

Ferredoxin-NADP+ reductase (FNR) in plants receives electrons from ferredoxin (Fd) and converts NADP+ to NADPH. The affinity between FNR and Fd is weakened by the allosteric binding of NADP(H) on FNR, which is considered as a part of negative cooperativity. We have been investigating the molecular mechanism of this phenomenon and proposed that the NADP(H)-binding signal is transferred to the Fd-binding region across the two domains of FNR, NADP(H)-binding domain and FAD-binding domain. In this study, we analyzed the effect of altering the inter-domain interaction of FNR on the negative cooperativity. Four site-directed FNR mutants at the inter-domain region were prepared, and their NADPH-dependent changes in the Km for Fd and physical binding ability to Fd were investigated. Two mutants, in which an inter-domain hydrogen bond was changed to a disulfide bond (FNR D52C/S208C) and an inter-domain salt bridge was lost (FNR D104N), were shown to suppress the negative cooperativity by using kinetic analysis and Fd-affinity chromatography. These results showed that the inter-domain interaction of FNR is important for the negative cooperativity, suggesting that the allosteric NADP(H)-binding signal is transferred to Fd-binging region by conformational changes involving inter-domain interactions of FNR.

Late stage specific Rv0109 (PE_PGRS1) protein of Mycobacterium tuberculosis induces mitochondria mediated macrophage apoptosis.

Mitochondria are the powerhouse of the cell and a critical cell signalling hub that decides the fate of the cell. Mycobacterium tuberculosis (Mtb) being a successful pathogen targets and controls the host mitochondria for pathogenesis. Various effector proteins of Mtb are also known to target host mitochondria which include few proteins of a unique Proline-Glutamate/Proline-Proline-Glutamate (PE/PPE) family exclusively present in pathogenic mycobacteria, but many of them are still uncharacterized. The present study investigates one such late expressing Rv0109 (PE_PGRS1) protein of Mtb. In-silico analysis predicted the presence of mitochondria targeting signal sequences in Rv0109 and its role in regulation of cysteine type endopeptidase (caspase) activity during apoptosis. Recombinant Rv0109 gets localized to mitochondria of THP1 macrophages as shown by confocal microscopy. Rv0109 was observed to induce mitochondrial stress which resulted in mitochondrial membrane depolarization, upregulation of mitochondrial superoxides and release of Cytochrome-C in the cytoplasm through flow cytometry. Depleted intracellular ATP was observed in THP1 macrophages in response to Rv0109. This mitochondrial stress in response to Rv0109 was observed to culminate in increased expression of pro-apoptotic Bax and Bim factors and caspase activation leading to macrophage apoptosis. Since Rv0109 is a late stage specific protein expressed within granuloma; mitochondria mediated apoptosis induced by Rv0109 may be explored for its role in granuloma maintenance and pathogen persistence.

Isolation of Cytochrome C for Proteomics with Lindqvist-type Polyiodate Modified Metal Organic Framework.

Separation and purification of Cytochrome C (Cyt-C) is important for proteomic. High efficient and selective pretreatment method for Cyt-C in real samples are always needed. Herein, polyniobate (K7H[Nb6O19]·13H2O, Nb6O19) is modified on a metal-organic framework MIL-125(Ti) through intermolecular hydrogen bonds and an aqueous-stable composite Nb6O19/MIL-125(Ti) is successfully prepared to pretreat complex protein sample. Protein adsorption studies have shown that Nb6O19/MIL-125(Ti) can promote the selective adsorption of Cyt-C due to the synergistic effect of electrostatic and hydrogen-bond interactions. At pH=10.0 (Britton-Robinson buffer), the adsorption efficiency of 300 µL 100 µg·mL-1 Cyt-C onto 1.0 mg Nb6O19/MIL-125(Ti) can reach 99.5%. The adsorption behavior of Cyt-C fits well with the Langmuir adsorption model, corresponding to a maximum theoretical adsorption capacity of 168.35 mg·g-1. Using 3 mol·L-1 NaCl as the eluent, a high elution efficiency of 92.19% is obtained. In addition, the results of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis confirm that Nb6O19/MIL-125(Ti) efficiently adsorbed Cyt-C from scrofa heart extraction. LC-MS/MS spectrometry results show that the purification of Cyt-C reduces the abundance from the 12th to the 154th place after Nb6O19/MIL-125(Ti) treatment. Moreover, low abundant proteins, e.g., Superoxide dismutase 1, IF rod domain-containing protein and Ubiquitin-60S ribosomal protein L40 were considerably enriched. These outcomes confirm the practicability of Nb6O19/MIL-125 (Ti) as a Cyt-C extractant has potential application value in scrofa heart proteomics.

Cytochrome c1-like is required for mitochondrial morphogenesis and individualization during spermatogenesis in Drosophila melanogaster.

The Drosophila testis is an excellent system for studying the process from germ stem cells to motile sperm, including the proliferation of male germ cells, meiosis of primary spermatocytes, mitochondrial morphogenesis, and spermatid individualization. We previously demonstrated that ocnus (ocn) plays an essential role in male germ cell development. Among those genes and proteins whose expression levels were changed as a result of ocn knockdown, cytochrome c1-like (cyt-c1L) was downregulated significantly. Here, we show that cyt-c1L is highly expressed in the testis of D. melanogaster. Knockdown or mutation of cyt-c1L in early germ cells of flies resulted in male sterility. Immunofluorescence staining showed that cyt-c1L knockdown testes had no defects in early spermatogenesis; however, in late stages, in contrast to many individualization complexes (ICs) composed of F-actin cones that appeared at different positions in control testes, no actin cones or ICs were observed in cyt-c1L knockdown testes. Furthermore, no mature sperm were found in the seminal vesicle of cyt-c1L knockdown testes whereas the control seminal vesicle was full of mature sperm with needle-like nuclei. cyt-c1L knockdown also caused abnormal mitochondrial morphogenesis during spermatid elongation. Excessive apoptotic signals accumulated in the base of cyt-c1L knockdown fly testes. These results suggest that cyt-c1L may play an important role in spermatogenesis by affecting the mitochondrial morphogenesis and individualization of sperm in D. melanogaster.

Silybin regulates P450s activity by attenuating endoplasmic reticulum stress in mouse nonalcoholic fatty liver disease.

Cytochrome P450s are important phase I metabolic enzymes located on endoplasmic reticulum (ER) involved in the metabolism of endogenous and exogenous substances. Our previous study showed that a hepatoprotective agent silybin restored CYP3A expression in mouse nonalcoholic fatty liver disease (NAFLD). In this study we investigated how silybin regulated P450s activity during NAFLD. C57BL/6 mice were fed a high-fat-diet (HFD) for 8 weeks to induce NAFLD, and were administered silybin (50, 100 mg ·kg-1 ·d-1, i.g.) in the last 4 weeks. We showed that HFD intake induced hepatic steatosis and ER stress, leading to significant inhibition on the activity of five primary P450s including CYP1A2, CYP2B6, CYP2C19, CYP2D6, and CYP3A in liver microsomes. These changes were dose-dependently reversed by silybin administration. The beneficial effects of silybin were also observed in TG-stimulated HepG2 cells in vitro. To clarify the underlying mechanism, we examined the components involved in the P450 catalytic system, membrane phospholipids and ER membrane fluidity, and found that cytochrome b5 (cyt b5) was significantly downregulated during ER stress, and ER membrane fluidity was also reduced evidenced by DPH polarization and lower polyunsaturated phospholipids levels. The increased ratios of NADP+/NADPH and PC/PE implied Ca2+ release and disruption of cellular Ca2+ homeostasis resulted from mitochondria dysfunction and cytochrome c (cyt c) release. The interaction between cyt c and cyt b5 under ER stress was an important reason for P450s activity inhibition. The effect of silybin throughout the whole course suggested that it regulated P450s activity through its anti-ER stress effect in NAFLD. Our results suggest that ER stress may be crucial for the inhibition of P450s activity in mouse NAFLD and silybin regulates P450s activity by attenuating ER stress.

Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1-7 Signals.

Cadmium (Cd) is a serious pollutant in the environment. Candesartan is an angiotensin II (Ang II) receptor antagonist with promising diverse health benefits. The current study is planned to investigate the hepatorenal protective effects of candesartan against Cd-induced hepatic and renal intoxication. Our results demonstrated that candesartan effectively attenuated Cd-induced hepatorenal intoxication, as evidenced by improving hepatic and renal function biomarkers. Besides, candesartan reversed hepatic and renal histopathological abrasions induced by Cd toxicity. Candesartan antioxidant effect was mediated by Nrf2 activation. Also, candesartan suppressed hepatorenal inflammation by modulating NF-κB/IκB. Moreover, candesartan attenuated Cd hepatorenal apoptosis by upregulating Bcl-2 and downregulating Bax and Cyt-C proteins. Interestingly, these effects are suggested to be an outcome of modulating of Ang II/Ang 1-7 signal. Overall, our findings revealed that candesartan could attenuate Cd-induced hepatorenal intoxication through modulation of Nrf2, NF-κB/IκB, Bax/Bcl-2/Cyt-c, and Ang II/Ang 1-7 signaling pathways.

Immunomodulatory role of mitochondrial DAMPs: a missing link in pathology?

In accordance with the endosymbiotic theory, mitochondrial components bear characteristic prokaryotic signatures, which act as immunomodulatory molecules when released into the extramitochondrial compartment. These endogenous immune triggers, called mitochondrial damage-associated molecular patterns (mtDAMPs), have been implicated in the pathogenesis of various diseases, yet their role remains largely unexplored. In this review, we summarise the available literature on mtDAMPs in diseases, with a special focus on respiratory diseases. We highlight the need to bolster mtDAMP research using a multipronged approach, to study their effect on specific cell types, receptors and machinery in pathologies. We emphasise the lacunae in the current understanding of mtDAMPs, particularly in their cellular release and the chemical modifications they undergo. Finally, we conclude by proposing additional effects of mtDAMPs in diseases, specifically their role in modulating the immune system.

Realgar (As4S4), a traditional Chinese medicine, induces acute promyelocytic leukemia cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway in vitro.

Acute promyelocytic leukemia (APL) is a specific subtype of acute myelogenous leukemia (AML) characterized by the proliferation of abnormal promyelocytes. Realgar, a Chinese medicine containing arsenic, can be taken orally. Traditional Chinese medicine physicians have employed realgar to treat APL for over a thousand years. Therefore, realgar may be a promising candidate for the treatment of APL. Nevertheless, the underlying mechanism behind realgar therapy is largely unclear. The present study aimed to investigate the effect of realgar on cell death in the APL cell line (NB4) in vitro and to elucidate the underlying mechanism. In this study, after APL cells were treated with different concentrations of realgar, the cell survival rate, apoptotic assay, morphological changes, ATP levels and cell cycle arrest were assessed. The expression of Bcl-2, Bax, Cytochrome C (Cyt-C) and apoptosis-inducing factor (AIF) at the mRNA and protein levels were also measured by immunofluorescence, quantitative PCR (qPCR) and Western blotting. We found that realgar could significantly inhibit APL cell proliferation and cell death in a time- and dose-dependent manner. Realgar effectively decreased the ATP levels in APL cells. Realgar also induced APL cell cycle arrest at the S and G2/M phases. Following realgar treatment, the mRNA and protein levels of Bcl-2 were significantly downregulated, whereas the levels of Bax, Cyt-C, and AIF were significantly upregulated. In summary, realgar can induce APL cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway, suggesting that realgar may be an effective therapeutic for APL.

Cyt-C Mediated Mitochondrial Pathway Plays an Important Role in Oocyte Apoptosis in Ricefield Eel (Monopterus albus).

Apoptosis plays a key role in the effective removal of excessive and defective germ cells, which is essential for sequential hermaphroditism and sex change in vertebrates. The ricefield eel, Monopterus albus is a protogynous hermaphroditic fish that undergoes a sequential sex change from female to male. Previous studies have demonstrated that apoptosis is involved in sex change in M. albus. However, the apoptotic signaling pathway is unclear. In the current study, we explored the underlying mechanism of apoptosis during gonadal development and focused on the role of the mitochondrial apoptosis signaling pathway in sex change in M. albus. Flow cytometry was performed to detect apoptosis in gonads at five sexual stages and ovary tissues exposed to hydrogen peroxide (H2O2) in vitro. Then the expression patterns of key genes and proteins in the mitochondrial pathway, death receptor pathway and endoplasmic reticulum (ER) pathway were examined. The results showed that the apoptosis rate was significantly increased in the early intersexual stage and then decreased with the natural sex change from female to male. Quantitative real-time PCR revealed that bax, tnfr1, and calpain were mainly expressed in the five stages. ELISA demonstrated that the relative content of cytochrome-c (cyt-c) in the mitochondrial pathway was significantly higher than that of caspase8 and caspase12, with a peak in the early intersexual stage, while the levels of caspase8 and caspase12 peaked in the late intersexual stage. Interestingly, the Pearson's coefficient between cyt-c and the apoptosis rate was 0.705, which suggests that these factors are closely related during the gonadal development of M. albus. Furthermore, the cyt-c signal was found to be increased in the intersexual stage by immunohistochemistry. After incubation with H2O2, the mRNA expression of mitochondrial pathway molecules such as bax, apaf-1, and caspase3 increased in ovary tissues. In conclusion, the present results suggest that the mitochondrial apoptotic pathway may play a more important role than the other apoptotic pathways in sex change in M. albus.

Biochemical, structural, and computational studies of a γ-carbonic anhydrase from the pathogenic bacterium Burkholderia pseudomallei.

Melioidosis is a severe disease caused by the highly pathogenic gram-negative bacterium Burkholderia pseudomallei. Several studies have highlighted the broad resistance of this pathogen to many antibiotics and pointed out the pivotal importance of improving the pharmacological arsenal against it. Since γ-carbonic anhydrases (γ-CAs) have been recently introduced as potential and novel antibacterial drug targets, in this paper, we report a detailed characterization of BpsγCA, a γ-CA from B. pseudomallei by a multidisciplinary approach. In particular, the enzyme was recombinantly produced and biochemically characterized. Its catalytic activity at different pH values was measured, the crystal structure was determined and theoretical pKa calculations were carried out. Results provided a snapshot of the enzyme active site and dissected the role of residues involved in the catalytic mechanism and ligand recognition. These findings are an important starting point for developing new anti-melioidosis drugs targeting BpsγCA.

DsbA-L interacts with VDAC1 in mitochondrion-mediated tubular cell apoptosis and contributes to the progression of acute kidney disease.

BACKGROUND: we demonstrated that disulfide-bond A oxidoreductase-like protein (DsbA-L) was involved in the progression of renal fibrosis. However, the precise function of DsbA-L in acute kidney injury (AKI), and the mechanisms involved, have yet to be elucidated. METHODS: We illustrate the DsbA-L interacted with VDAC1 by co-IP (co-immunoprecipitation) in vitro and vivo, and found the interaction parts of them by mutation experiment. The above findings were verified by co-localization of them. In addition, we constructed the two model of PT-DsbA-L and VDAC1 KO mice to verify the function of DsbA-L and VDAC1 in models of VAN, CLP and I/R-induced AKI. FINDINGS: The PT-DsbA-L-KO mice showed amelioration of I/R, VAN-, and CLP-induced AKI progression via the downregulation of VDAC1. Finally, we confirmed these changes in signal molecules by examining in HK-2 cells and kidney biopsies taken from patients with ischemic or acute interstitial nephritis (AIN)-induced AKI. Mechanistically, DsbA-L interacted with amino acids 9-13 and 22-27 of VDAC1 in the mitochondria of BUMPT cells to induce renal cell apoptosis and mitochondrial injury. INTERPRETATION: This work suggested that DsbA-L, located in the proximal tubular cells, drives the progression of AKI, by directly upregulating the levels of VDAC1.Running Title: The role of DsbA-L in AKI FUNDING: National Natural Science Foundation of China, a grant from Key Project of Hunan provincial science and technology innovation, Department of Science and Technology of Hunan Province project of International Cooperation and Exchanges, Changsha Science and Technology Bureau project, Natural Science Foundation of Hunan Province, Fundamental Research Funds for the Central Universities of Central South University, Hunan Provincial Innovation Foundation For Postgraduate China Hunan Provincial Science and Technology Department.

Target-modulated competitive binding and exonuclease I-powered strategy for the simultaneous and rapid detection of biological targets.

Simultaneous multiple-target detection is essential for the prevention, identification, and treatment of numerous diseases. In this study, a novel strategy based on target-modulated competitive binding and exonuclease I (Exo I)-powered signal molecule release was established with the advantages of rapid response and high selectivity and sensitivity. The strategy holds substantial potential for the development of versatile platforms for the simultaneous detection of biological targets. To mitigate the low load capacity and time-consuming responsive process of the Zr-MOF system, UiO-67 was chosen to replace UiO-66 (a typical Zr-MOF) as the nanocarrier for encapsulating more signal molecules, whereby the assembled double-stranded DNA (dsDNA) structures of UiO-67 acted as gatekeepers to form dsDNA-functionalized MOFs. Additionally, Exo I was introduced into the system to accelerate the release of the signal molecules. In the presence of biological targets, the competitive binding between the targets and aptamers caused the hydrolysis of the free DNA sequence by Exo I, promoting the release of signal molecules and leading to a rapid and significant increase in the fluorescence intensity. For adenosine triphosphate (ATP) and cytochrome c (cyt c), which were chosen as model biological targets, this sensor displayed detection limits as low as 5.03 and 6.11 fM, respectively. Moreover, the developed biosensor was successfully applied to the simultaneous detection of ATP and cyt c in spiked serum samples. Therefore, this strategy provides guidance for further research of biosensors for simultaneous multiple-target detection and propels the application of MOF carriers in biomedicine.

In vivo Study of a Newly Synthesized Chromen-4-one Derivative as an Antitumor Agent against HCC.

BACKGROUND: Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromene activity vary between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behaviors other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors, pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation, and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and anti-tumor activity. METHODS: In the present study, hepatocellular cancer (HCC) induced by diethylnitrosamine (DEN) in rats and then treated with the new chromene derivative and the parameters TNF-α, VEGF, p53, Cyt C, MMP-9, Bcl2, and Bax were measured. RESULTS: The treatment strategy Ch compound is to downregulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently control other factors such as p53, Cyt C, and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN-induced HCC in rats. CONCLUSION: The ability of the new Ch derivative to control the primary initiators of HCC such as TNF-α offers this derivative an anti-tumor activity and encourages further researches to follow and monitor its effect on the molecular level.

Interaction of human hemoglobin (HHb) and cytochrome c (Cyt c) with biogenic chloroxine-conjugated silver nanoflowers: spectroscopic and molecular docking approaches.

In this research, the biological activity of the antibacterial drug Chloroxine-conjugated biogenic AgNPs (COX-AgNPs) was investigated in simulated physiological conditions (pH = 7.40). Different spectroscopic methods such as UV-visible, fluorescence, and circular dichroism spectroscopic and docking simulation were employed to evaluate the structural changes in the most important blood proteins (human hemoglobin (HHb) and Cytochrome c (Cyt c)) in the presence of COX-AgNPs. The results showed that the COX-AgNPs can bind to HHb and Cyt c and the secondary structure of these proteins remains unchanged, which is crucial in providing insights into the side effects of newly synthesized drugs on their carriers.Communicated by Ramaswamy H. Sarma.