An Insight into Multisystem Inflammatory Syndrome in Adults Associated with Recent SARS-COV-2 Infection: A Case Series.

IMPORTANCE: Multisystem inflammatory syndrome-adults (MIS-A) occur in the postacute coronavirus disease 2019 (COVID-19) period with a diverse clinical presentation. A high index of suspicion, early recognition, diagnosis, and treatment of MIS-A might alleviate COVID-19-related morbidity and mortality. OBJECTIVE: To report seven cases of MIS-A with evidence of recent COVID-19 infection. This is a case series-based study and presents bona fide experiences in terms of main findings and treatment options. MATERIALS AND METHODS: It is a retrospective observational study. We retrospectively collected data on all patients who were diagnosed and treated for MIS-A during the period after the second wave of COVID-19 in India, that is, from June 2021 to November 2021and who were hospitalized in the author's unit. All patients fulfilled the morbidity and mortality weekly report (MMWR) criteria for multisystem inflammatory syndrome in adults. The presenting symptoms, clinical and laboratory parameters, management, and outcome of these seen cases are discussed in this case series-based review.. RESULTS: Data from seven patients were analyzed. Six of them were male, and one patient was female. The median age was 65 years. Four patients had a history of vaccination for COVID-19, three had a history of COVID-19 symptomatic infection in the past, and one patient had contact with COVID-19 in the previous 12 weeks. None of them tested positive for COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) test, and all had positive COVID-19 serology. The commonest extrapulmonary organ involved were the cardiovascular and renal systems, followed by the gastrointestinal and central nervous systems (CNS). All had evidence of hyperinflammation. Intravenous immunoglobulin (IVIg) was used in four patients, and steroids were used in all seven patients. The median length of stay (LOS) was 11 days. One patient succumbed to multiorgan failure. CONCLUSIONS: Multisystem inflammatory syndrome (MIS) can affect children (MIS-C) as well as adults (MIS-A). MIS-A is a serious, life-threatening, hyperinflammatory febrile syndrome associated with recent COVID-19 infection and involves multiple organs like the heart, lungs, kidneys, brain, gastrointestinal organs, skin, eyes etc. Clinical suspicion and testing for evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are needed to identify and treat adults suspected to have MIS-A. This case series demonstrates that even the elderly population can be affected and that administration of IVIg and steroids are effective options in management in addition to the usual "standard of care" treatment. Early recognition and prompt treatment of MIS-A could improve clinical outcomes and reduce the mortality rate.

CAMK2D serves as a molecular scaffold for RNF8-MAD2 complex to induce mitotic checkpoint in glioma.

MAD2 is a spindle assembly checkpoint protein that participates in the formation of mitotic checkpoint complex, which blocks mitotic progression. RNF8, an established DNA damage response protein, has been implicated in mitotic checkpoint regulation but its exact role remains poorly understood. Here, RNF8 proximity proteomics uncovered a role of RNF8-MAD2 in generating the mitotic checkpoint signal. Specifically, RNF8 competes with a small pool of p31comet for binding to the closed conformer of MAD2 via its RING domain, while CAMK2D serves as a molecular scaffold to concentrate the RNF8-MAD2 complex via transient/weak interactions between its p-Thr287 and RNF8's FHA domain. Accordingly, RNF8 overexpression impairs glioma stem cell (GSC) mitotic progression in a FHA- and RING-dependent manner. Importantly, low RNF8 expression correlates with inferior glioma outcome and RNF8 overexpression impedes GSC tumorigenicity. Last, we identify PLK1 inhibitor that mimics RNF8 overexpression using a chemical biology approach, and demonstrate a PLK1/HSP90 inhibitor combination that synergistically reduces GSC proliferation and stemness. Thus, our study has unveiled a previously unrecognized CAMK2D-RNF8-MAD2 complex in regulating mitotic checkpoint with relevance to gliomas, which is therapeutically targetable.

PLK1 inhibition selectively induces apoptosis in ARID1A deficient cells through uncoupling of oxygen consumption from ATP production.

Inhibitors of the mitotic kinase PLK1 yield objective responses in a subset of refractory cancers. However, PLK1 overexpression in cancer does not correlate with drug sensitivity, and the clinical development of PLK1 inhibitors has been hampered by the lack of patient selection marker. Using a high-throughput chemical screen, we discovered that cells deficient for the tumor suppressor ARID1A are highly sensitive to PLK1 inhibition. Interestingly this sensitivity was unrelated to canonical functions of PLK1 in mediating G2/M cell cycle transition. Instead, a whole-genome CRISPR screen revealed PLK1 inhibitor sensitivity in ARID1A deficient cells to be dependent on the mitochondrial translation machinery. We find that ARID1A knock-out (KO) cells have an unusual mitochondrial phenotype with aberrant biogenesis, increased oxygen consumption/expression of oxidative phosphorylation genes, but without increased ATP production. Using expansion microscopy and biochemical fractionation, we see that a subset of PLK1 localizes to the mitochondria in interphase cells. Inhibition of PLK1 in ARID1A KO cells further uncouples oxygen consumption from ATP production, with subsequent membrane depolarization and apoptosis. Knockdown of specific subunits of the mitochondrial ribosome reverses PLK1-inhibitor induced apoptosis in ARID1A deficient cells, confirming specificity of the phenotype. Together, these findings highlight a novel interphase role for PLK1 in maintaining mitochondrial fitness under metabolic stress, and a strategy for therapeutic use of PLK1 inhibitors. To translate these findings, we describe a quantitative microscopy assay for assessment of ARID1A protein loss, which could offer a novel patient selection strategy for the clinical development of PLK1 inhibitors in cancer.

Fumonisin B1 induces poly (ADP-ribose) (PAR) polymer-mediated cell death (parthanatos) in neuroblastoma.

Fumonisin B1 (FB1) is a well-known mycotoxin produced by Fusarium spp. and has a wide range of dose-dependent toxic effects, including nephrotoxicity, hepatotoxicity, and neurotoxicity. This research illustrated that FB1 exerts its toxicity in the neuroblastoma cell line through a distinct cell-death pathway called parthanatos. FB1 can cause excessive DNA strand breaks, leading to poly (ADP-ribose) polymerase-1 (PARP-1) overactivation and cell death. In this study, we used 50 µM FB1-treated SH-SY5Y neuroblastoma cells to elucidate the signaling pathway of FB1-induced parthanatos. We observed that FB1-induced cell death is caspase-independent and accompanied by rapid activation of PARP-1, c-Jun N-terminal kinase activation, reactive oxygen species (ROS) generation, and intracellular calcium increase. FB1 treatment also increased endoplasmic reticulum stress due to the rapid increase of calcium ions and ROS levels. In addition, FB1 induced massive DNA damage and chromatin decondensation. We also observed that apoptosis-inducing factor nuclear translocation and PAR accumulation were associated with the necroptosis signal.

Study of maternal outcome in referral obstetric cases in a tertiary care centre.

INTRODUCTION: To identify the pattern of Obstetric referral to our hospital and the primary reasons for referral, so as to implement measures to reduce unnecessary referrals and to reduce maternal mortality and morbidity. METHOD: All the referred cases for obstetrics indications above 20 weeks were analysed for cause of referral, their condition and outcome for a period of 6 months from January 2016 to June 2016. RESULTS: According to our study out of a total of 10172 delivered patients, 1014 (9.96%) cases were referred patients. Maximum cases i.e. 713 (70. 3%) were in the age group of 21-30. Most of the cases 678 (66.86%) did not receive any treatment at referral hospital before being referred. Only 27.52% patients were referred with referral slips/chit etc., having adequate information and 40.24% of cases were delayed referrals. 183 (18.04%) patients required intensive care unit admission. CONCLUSION: The present study showed that illiteracy and ignorance of female regarding healthcare requirements and poor infrastructure came out to be a major contributor of poor pregnancy outcome. Timely referral is crucial for a satisfactory maternal and fetal outcome. To reduce the number of unnecessary referrals and to reduce burden on tertiary care hospitals, health care workers should be trained in essential and emergency obstetric care which will help in reducing morbidity and mortality.

Safety and Efficacy of Intra-caesarean IUCD: A Prospective Study at a Tertiary Care Centre.

OBJECTIVE: To assess the safety and efficacy of postpartum IUCD in caesarean section patients. METHODS: This prospective observational study included 200 women, who gave informed consent for postpartum intrauterine contraceptive device (PPIUCD) insertion during caesarean section from January 2013 to May 2014. These patients were followed up at 6 weeks and 6 months. RESULTS: There were no major complaints in either group in post-operative period. At 6-month follow-up in PPIUCD users, 89.5% of patients continued to use this method. 5.5% were lost to follow-up, 2.5% had spontaneous expulsion, and 2.5% removed the IUCD due to various reasons. Eight per cent of patients who wanted removal of IUCD in the second follow-up were counselled to continue, and they did so. CONCLUSION: The results of our study suggest that immediate intra-caesarean IUCD insertion appears to be a safe and effective method of contraception. The acceptability of intra-caesarean IUCD was high, and its continuation rate has demonstrated its safety.

Exosomes as Emerging Pro-Tumorigenic Mediators of the Senescence-Associated Secretory Phenotype.

Communication between cells is quintessential for biological function and cellular homeostasis. Membrane-bound extracellular vesicles known as exosomes play pivotal roles in mediating intercellular communication in tumor microenvironments. These vesicles and exosomes carry and transfer biomolecules such as proteins, lipids and nucleic acids. Here we focus on exosomes secreted from senescent cells. Cellular senescence can alter the microenvironment and influence neighbouring cells via the senescence-associated secretory phenotype (SASP), which consists of factors such as cytokines, chemokines, matrix proteases and growth factors. This review focuses on exosomes as emerging SASP components that can confer pro-tumorigenic effects in pre-malignant recipient cells. This is in addition to their role in carrying SASP factors. Transfer of such exosomal components may potentially lead to cell proliferation, inflammation and chromosomal instability, and consequently cancer initiation. Senescent cells are known to gather in various tissues with age; eliminating senescent cells or blocking the detrimental effects of the SASP has been shown to alleviate multiple age-related phenotypes. Hence, we speculate that a better understanding of the role of exosomes released from senescent cells in the context of cancer biology may have implications for elucidating mechanisms by which aging promotes cancer and other age-related diseases, and how therapeutic resistance is exacerbated with age.

Immunosuppressive potential of astemizole against LPS activated T cell proliferation and cytokine secretion in RAW macrophages, zebrafish larvae and mouse splenocytes by modulating MAPK signaling pathway.

In this study, the immunomodulatory effects of astemizole (AST) against lipopolysaccharide (LPS) mediated T cell proliferation and induction of inflammation in RAW macrophages (in vitro), and zebrafish larvae (in vivo) were determined. AST significantly suppressed the phagocytic activity of macrophages (3.303 ±â€¯0.115) and inhibited lysosomal enzyme secretion (13.27 ±â€¯2.52) induced by LPS (100 ng/ml). Moreover, AST subdued the morphological deformities such as yolk sac edema (YSE) and spinal curvature curving (SC) by inhibiting ROS generation in zebrafish larvae 24 h after microinjection of LPS (0.5 mg/ml). AST was also shown to inhibit the production of the major cytokines TNF-α (150.8 ±â€¯0.6), IL-1ß (276.5 ±â€¯1.6), and PGE2 (194.6 ±â€¯0.6) pg/ml in RAW macrophages. It also subdued the ROS induced iNOS and COX-2 generated in response to LPS mediated immune dysfunctions in zebrafish larvae. These results suggested the immunosuppression effect of AST. Furthermore, induction of immune-suppression due to AST resulted in significant down-regulation of innate immunity directed by MAPK (p38, ERK and JNK), which was found to be associated with decreased production of acute inflammatory mediators both in vitro and in vivo. To confirm its activity, splenocytes were prepared using BALB/c mice and a mitogen activated splenocyte proliferation assay was also performed. Our findings suggest that AST has the ability to inhibit T cell proliferation and cytokine secretion both in vitro and in vivo by interfering with MAPK signaling pathway. Taken together, our results showed the potential of AST as a countermeasure to immune dysfunction and suggest its use as immunosuppressant compound in inflammatory disease.

Autophagy Governs Protumorigenic Effects of Mitotic Slippage-induced Senescence.

The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and "slip" into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G1 arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment.Implications: Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. Mol Cancer Res; 16(11); 1625-40. ©2018 AACR.

Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells.

Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitumor effects of vitexin and its underlying mechanisms in a multi-drug resistant human colon cancer cell line (HCT-116DR), which exhibits higher levels of multidrug-resistant protein 1 (MDR1) expression as compared with its parental cell line (HCT-116). Here, we observed that vitexin suppressed MDR-1 expression and activity in HCT-116DR cells and showed cytotoxic effect in HCT-116DR cells by inhibiting autophagy and inducing apoptosis in a concentration-dependent manner. Additionally, vitexin treatment caused cleavage of caspase-9 and caspase-3, and upregulated the expression of the pro-apoptotic proteins, BID and Bax. Moreover, the expression of autophagy-related proteins, such as ATG5, Beclin-1 and LC3-II, was markedly reduced by vitexin treatment. Furthermore, in vivo experiments showed that vitexin induced apoptosis and suppressed tumor growth in HCT-116DR xenograft model. These results revealed that vitexin induced apoptosis through suppression of autophagy in vitro and in vivo and provide insight into the therapeutic potential of vitexin for the treatment of chemo-resistant colorectal cancer.

Vitexin confers HSF-1 mediated autophagic cell death by activating JNK and ApoL1 in colorectal carcinoma cells.

Heat shock transcription factor-1 (HSF-1) guards the cancerous cells proteome against the alterations in protein homeostasis generated by their hostile tumor microenvironment. Contrasting with the classical induction of heat shock proteins, the pro-oncogenic activities of HSF-1 remains to be explored. Therefore, cancer's fragile proteostatic pathway governed by HSF-1 could be a potential therapeutic target and novel biomarker by natural compounds. Vitexin, a natural flavonoid has been documented as a potent anti-tumor agent on various cell lines. However, in the present study, when human colorectal carcinoma HCT-116 cells were exposed to vitexin, the induction of HSF-1 downstream target proteins, such as heat shock proteins were suppressed. We identified HSF-1 as a potential molecular target of vitexin that interact with DNA-binding domain of HSF-1, which inhibited HSF-1 oligomerization and activation (in silico). Consequently, HSF-1 hyperphosphorylation mediated by JNK operation causes transcriptional inactivation of HSF-1, and supported ROS-mediated autophagy induction. Interestingly, in HSF-1 immunoprecipitated and silenced HCT-116 cells, co-expression of apolipoprotein 1 (ApoL1) and JNK was observed which promoted the caspase independent autophagic cell death accompanied by p62 downregulation and increased LC3-I to LC3-II conversion. Finally, in vivo findings confirmed that vitexin suppressed tumor growth through activation of autophagic cascade in HCT-116 xenograft model. Taken together, our study insights a probable novel association between HSF-1 and ApoL-1 was established in this study, which supports HSF-1 as a potential target of vitexin to improve treatment outcome in colorectal cancer.

Novel quercetin derivative TEF induces ER stress and mitochondria-mediated apoptosis in human colon cancer HCT-116 cells.

Although quercetin is very well known for its anticancer activity, however it shows some drawbacks. Herein, we have evaluated the apoptotic effect TEF (5, 3'-dihydroxy-3, 7, 4'-triethoxyflavone), a newly synthesized quercetin derivative on HCT-116 colon cancer cells. After 24h of treatment, the proliferation of colon cancer cells was inhibited by TEF. TEF induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated cytoplasmic and mitochondrial reactive oxygen species (ROS) levels. TEF treatment causes elevation of IRE1-α and activates calcium ions (Ca2+) with concomitant increase in JNK levels. Elevated Ca2+ ion translocates from ER to mitochondria which leads to ROS release and oxidative stress. TEF treatment further elevated levels of pro-apoptotic factors and down-regulated the level of Bcl2. TEF led to activation of mito-JNK (mitochondrial JNK), which plays a crucial role in activation of oxidative stress and caspase mediated apoptotic cell death. Moreover, JNK inhibition shown to suppress TEF induced apoptosis in HCT-116 colon cancer cells. Therefore, this study reveals the apoptotic role of TEF against HCT-116 cell line via IRE1-α and mito-JNK pathway.

5-Hydroxy-7-Methoxyflavone Triggers Mitochondrial-Associated Cell Death via Reactive Oxygen Species Signaling in Human Colon Carcinoma Cells.

Plant-derived compounds are an important source of clinically useful anti-cancer agents. Chrysin, a biologically active flavone found in many plants, has limited usage for cancer chemotherapeutics due to its poor oral bioavailability. 5-Hydroxy-7-methoxyflavone (HMF), an active natural chrysin derivative found in various plant sources, is known to modulate several biological activities. However, the mechanism underlying HMF-induced apoptotic cell death in human colorectal carcinoma cells in vitro is still unknown. Herein, HMF was shown to be capable of inducing cytotoxicity in HCT-116 cells and induced cell death in a dose-dependent manner. Treatment of HCT-116 cells with HMF caused DNA damage and triggered mitochondrial membrane perturbation accompanied by Cyt c release, down-regulation of Bcl-2, activation of BID and Bax, and caspase-3-mediated apoptosis. These results show that ROS generation by HMF was the crucial mediator behind ER stress induction, resulting in intracellular Ca2+ release, JNK phosphorylation, and activation of the mitochondrial apoptosis pathway. Furthermore, time course study also reveals that HMF treatment leads to increase in mitochondrial and cytosolic ROS generation and decrease in antioxidant enzymes expression. Temporal upregulation of IRE1-α expression and JNK phosphorylation was noticed after HMF treatment. These results were further confirmed by pre-treatment with the ROS scavenger N-acetyl-l-cysteine (NAC), which completely reversed the effects of HMF treatment by preventing lipid peroxidation, followed by abolishment of JNK phosphorylation and attenuation of apoptogenic marker proteins. These results emphasize that ROS generation by HMF treatment regulates the mitochondrial-mediated apoptotic signaling pathway in HCT-116 cells, demonstrating HMF as a promising pro-oxidant therapeutic candidate for targeting colorectal cancer.

Astemizole-Histamine induces Beclin-1-independent autophagy by targeting p53-dependent crosstalk between autophagy and apoptosis.

Apoptosis and autophagy are genetically regulated, evolutionarily conserved processes that can jointly seal cancer cell fates, and numerous death stimuli are capable of activating either pathway. Although crosstalk between apoptosis and autophagy is quite complex and sometimes contradictory, it remains a key factor determining the outcomes of death-related pathologies such as cancer. In the present study, exposure of MCF-7 breast cancer cells to HIS and the H1 receptor antagonist AST both alone and together with HIS (AST-HIS) led to generation of intracellular ROS, which induced massive cellular vacuolization through dilation of the ER and mitochondria. Consequently, apoptosis by Bax translocation, cytochrome c release, and caspase activation were triggered. In addition, AST-HIS caused ER stress-induced autophagy in MCF-7 cells, as evidenced by an increased LC3-II/LC3-I ratio, with surprisingly no changes in Beclin-1 expression. Non-canonical autophagy was induced via p53 phosphorylation, which increased p53-p62 interactions to enhance Beclin-1-independent autophagy as evidenced by immunocytochemistry and immunoprecipitation. In the absence of Beclin-1, enhanced autophagy further activated apoptosis through caspase induction. In conclusion, these findings indicate that AST-HIS-induced apoptosis and autophagy can be regulated by ROS-mediated signaling pathways.

Glutathione-S-transferase omega 1 (GSTO1-1) acts as mediator of signaling pathways involved in aflatoxin B1-induced apoptosis-autophagy crosstalk in macrophages.

Aflatoxin B1 (AFB1) is the most toxic aflatoxin species and has been shown to be associated with specific as well as non-specific immune responses. In the present study, using murine macrophage Raw 264.7 cells as a model, we report that short exposure (6h) to AFB1 caused an increase in the cellular calcium pool in mitochondria, which in turn elevated reactive oxygen species (ROS)-mediated oxidative stress and led to loss of mitochondrial membrane potential and ultimately c-Jun N-terminal kinases (JNK)-mediated caspase-dependent cell death. On the contrary, longer exposure (12h) to AFB1 reduced JNK phosphorylation and cell death in macrophages. Measurement of autophagic flux demonstrated that autophagy induction through the canonical pathway was responsible for suppressing AFB1-induced apoptosis after 12h. As a detailed molecular mechanism, we found that the unfolded protein response (UPR) machinery was active at 12h post-exposure to AFB1 and induced cytoprotective autophagy as confirmed by determination of major autophagic markers. Inhibition of autophagy by Beclin-1 siRNA also resulted in JNK-mediated cell death. We further established that glutathione S transferase omega1-1 (GSTO1-1), a specific class of GST, was the responsible factor between apoptosis and autophagy crosstalk. Targeting of GSTO1-1 increased JNK-mediated apoptosis by 2-fold compared to the control, whereas autophagy rate was reduced. Thus, increased expression of GSTO1-1 was associated with increased protein glutathionylation, an important protein modification in response to cellular redox status.

Potential role of vitexin in alleviating heat stress-induced cytotoxicity: Regulatory effect of Hsp90 on ER stress-mediated autophagy.

AIMS: Cells possess multiple methods for counteracting the deleterious consequences of stress induced by physical and chemical stimuli. Heat stress causes variations in the cellular environment, leading to cellular morbidity or mortality. Natural compounds that contain phenolic antioxidants, offer various therapeutic and biological activities. Vitexin, a natural flavonoid, has been reported to treat various pathologies due to its multifaceted effects. Herein, we investigated the therapeutic efficacy of vitexin and its underlying mechanism against heat stress in human lung epithelial cells. MAIN METHODS: Effect of vitexin on the expression of molecular chaperones, antioxidant enzymes, mitogen activated protein kinases (MAPKs), endoplasmic reticulum (ER)-stress and autophagy was measured by immunoblotting. qRT-PCR and EMSA were performed for Hsp90 expression and HSF-1 binding affinity. Cell viability was assessed by MTT and LDH assays. Detection of autophagy was confirmed by acridine orange staining. Role of Hsp90 inhibition on signaling pathways was elucidated by using specific chemical inhibitor, radicicol. KEY FINDINGS: Whereas hyperthermia reduced cell viability, result of MTT and LDH assays showed that vitexin pre-treatment enhanced cell viability after heat stress. EMSA analysis shows DNA binding affinity of HSF-1 during heat stress. Vitexin upregulated Hsp90 expression, subsequently activating ER-stress induced autophagy. Modulation of MAPKs expression and fluorescence image analysis showed vacuole accumulation, indicating autophagic flux in cells. Hsp90 inhibition reversed the effect of vitexin and activates the apoptosis pathway. SIGNIFICANCE: Our data suggest that vitexin can protect against hyperthermic cellular injury by induction of Hsp90 expression, antioxidant activity and MAPKs via ER stress-induced autophagy.

Morin hydrate attenuates the acrylamide-induced imbalance in antioxidant enzymes in a murine model.

Liver diseases are among the most serious health issues nowadays. Hepatocellular carcinoma, one of the most lethal types of cancer worldwide, can be caused by chemically-induced oxidative stress. In the present study, we aimed to evaluate the protective effects of morin hydrate (MH) against acrylamide (AA)-induced hepatotoxicity in male ICR mice. The mice were randomly allocated into 4 groups [the control, the group subcutaneously injected with AA alone (50 mg/kg body weight), the group subcutaneously injected with AA (50 mg/kg body weight) and MH (5 mg/kg body weight) and the group subcutaneously injected with AA (50 mg/kg body weight) and MH (15 mg/kg body weight) for 5 consecutive days]. Histopathological evaluations were performed and the levels of serum hepatic enzymes were analyzed to determine initial liver injury, and the mice in the AA-treated groups were compared with the mice receiving no treatment and with the mice administered MH in combination with AA. Furthermore, oxidative stress, hepatic inflammation and the levels of DNA damage-related markers were evaluated to determine the extent of liver damage induced by AA within a short-term period. The subcutaneous administration of AA induced severe hepatic injury, and combined treatment with AA and MH resulted in a significant improvement in all evaluated parameters. This recovery was most obvious in the group receiving AA and 15 mg/kg body weight dose of MH. The findings of our study demonstrated that MH protected mice from severe hepatic injury induced by AA. Moreover, MH is a natural polyphenolic compound, and thus it has potential for use in the treatment of severe liver diseases, in place of many synthetic drugs.

Apoptotic properties of polysaccharide isolated from fruiting bodies of medicinal mushroom Fomes fomentarius in human lung carcinoma cell line.

Mushrooms are known to complement chemotherapy and radiation therapy by countering the side effects of cancer. Recently, there has been great interest in isolation of novel bioactive compounds from mushrooms due to their numerous health beneficial effects. Chemically water-extractable polysaccharide (MFKF-AP1ß), with a molecular weight of 12 kDa, was isolated from fruiting bodies of mushroom Fomes fomentarius. In this research, we investigated the anti-tumor effects of MFKF-AP1ß on human lung carcinoma A549 cells. Results showed that MFKF-AP1ß markedly inhibited A549 cell growth in a dose-dependent manner based on the amount of lactate dehydrogenase (LDH) released and morphological alterations. In addition, MFKF-AP1ß induced cellular apoptosis by causing single-stranded DNA breakage, as evidenced by apoptosis assay. Furthermore, MFKF-AP1ß (25-100 µg/ml) significantly induced single-stranded DNA breakage in A549 cells, as shown by comet assay. Taken together, our results demonstrate that MFKF-AP1ß has strong anti-tumor effects mediated through induction of apoptosis. Therefore, MFKF-AP1ß could be useful in lung chemotherapy.