Cancer-secreted exosomal miRNAs are emerging mediators of cancer-stromal cross-talk in the tumor environment. Our previous miRNAs array of cervical squamous cell carcinoma (CSCC) clinical specimens ...identified upregulation of miR-221-3p. Here, we show that miR-221-3p is closely correlated with peritumoral lymphangiogenesis and lymph node (LN) metastasis in CSCC. More importantly, miR-221-3p is characteristically enriched in and transferred by CSCC-secreted exosomes into human lymphatic endothelial cells (HLECs) to promote HLECs migration and tube formation in vitro, and facilitate lymphangiogenesis and LN metastasis in vivo according to both gain-of-function and loss-of-function experiments. Furthermore, we identify vasohibin-1 (VASH1) as a novel direct target of miR-221-3p through bioinformatic target prediction and luciferase reporter assay. Re-expression and knockdown of VASH1 could respectively rescue and simulate the effects induced by exosomal miR-221-3p. Importantly, the miR-221-3p-VASH1 axis activates the ERK/AKT pathway in HLECs independent of VEGF-C. Finally, circulating exosomal miR-221-3p levels also have biological function in promoting HLECs sprouting in vitro and are closely associated with tumor miR-221-3p expression, lymphatic VASH1 expression, lymphangiogenesis, and LN metastasis in CSCC patients. In conclusion, CSCC-secreted exosomal miR-221-3p transfers into HLECs to promote lymphangiogenesis and lymphatic metastasis via downregulation of VASH1 and may represent a novel diagnostic biomarker and therapeutic target for metastatic CSCC patients in early stages.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In conjunction with the classical functions of regulating intestinal, bone, and kidney calcium and phosphorus absorption, as well as bone mineralization of vitamin D, the population-based association ...between low vitamin D status and increased cancer risk is now generally accepted. Inflammation is causally related to oncogenesis. It is widely thought that vitamin D plays an important role in the modulation of the inflammation system by regulating the production of inflammatory cytokines and immune cells, which are crucial for the pathogenesis of many immune-related diseases. Mechanistic studies have shown that vitamin D influences inflammatory processes involved in cancer progression, including cytokines, prostaglandins, MAP kinase phosphatase 5 (MKP5), the nuclear factor kappa B (NF-κB) pathway, and immune cells. Multiple studies have shown that vitamin D has the potential to inhibit tumor development by interfering with the inflammation system. The present review summarizes recent studies of the mechanisms of vitamin D on regulating the inflammation system, which contributes to its potential for cancer prevention and therapy. This review helps answer whether inflammation mediates a causal relationship between vitamin D and tumorigenesis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A range of polyoxotitanium clusters (PTCs) was constructed by tuning the type of acid (inorganic and organic) in alcoholic solvents, from Ti4, Ti6, Ti9, Ti11, to Ti16. After removing the tBuOH ...solvent, giant carboxylate‐stabilized Ti44‐oxo clusters in which propionic acid serves as both ligand and solvent were ultimately obtained. The four labile sites in the Ti44 cluster core can be occupied by two formate and two propionate anions (PTC‐165) or a pair of glutarate (PTC‐166) or 3‐methylglutarate anions (PTC‐167). According to the synthesis of PTC‐155 to PTC‐167, the propionic acid solvent plays a crucial role in the construction of giant Ti oxo clusters. Their one‐pot yields, which readily reached up to 8.75 g for PTC‐165 and 9.96 g for PTC‐166, proved the feasibility of large‐scale preparation. More interestingly, the obtained Ti44‐oxo clusters are almost completely surrounded by carboxylate ligands, which allow them to retain crystalline stability in air for about three weeks and in either acidic or basic aqueous solution over a wide pH range for at least 6 h. In addition, PTC‐165 and PTC‐166 exhibit excellent UV photocurrent response and reversible photochromic effect. This work provides a systematic approach for constructing high‐nuclearity and stable PTCs on a large scale, which is significant for future applications of PTC‐based photochemical devices.
Scale it up! A facile acid‐controlled approach has been developed for the synthesis of a range of polyoxotitanium clusters (PTCs; see figure). By using propionic acid as both ligand and solvent, Ti44‐oxo clusters with four labile sites and reversible photochromic behavior were prepared. Moreover, large‐scale synthesis of the Ti44‐oxo clusters was achieved, with one‐pot yields scaled up to about 10 g.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to ...infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology.
To better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients.
Altered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients.
Our results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis‐inducing agents have great potential as new antitumor candidates. Here, we report a IrIII complex (Ir1) ...containing a ferrocene‐modified diphosphine ligand that localizes in lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton‐like reaction, produce hydroxyl radicals, induce lipid peroxidation, down‐regulate glutathione peroxidase 4, and result in ferroptosis. RNA sequencing analysis shows that Ir1 can significantly affect pathways related to ferroptosis and cancer immunity. Accordingly, Ir1 can induce immunogenic cells death and suppress tumor growth in vitro, regulate T cell activity and immune microenvironments in vivo. In conclusion, we show the potential of small molecules with ferroptosis‐inducing capabilities for effective cancer immunotherapy.
Ferroptosis‐inducing agents have potential as antitumor candidates. A ferrocene‐modified IrIII complex with Fenton‐like catalytic activity is used to disturb the cellular redox balance, which leads to lipid peroxidation and ferroptosis of cancer cells. Ferroptosis induced by the IrIII complex causes immunogenic cell death (ICD) of cancer cell in vitro, which enhances cancer immune response in vivo.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a ...comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% CI 45.4-54.8) of COVID-19 survivors for up to 12 months after infection. The most common investigation findings included abnormalities on lung CT (56.9%, 95% CI 46.2-67.3) and abnormal pulmonary function tests (45.6%, 95% CI 36.3-55.0), followed by generalized symptoms, such as fatigue (28.7%, 95% CI 21.0-37.0), psychiatric symptoms (19.7%, 95% CI 16.1-23.6) mainly depression (18.3%, 95% CI 13.3-23.8) and PTSD (17.9%, 95% CI 11.6-25.3), and neurological symptoms (18.7%, 95% CI 16.2-21.4), such as cognitive deficits (19.7%, 95% CI 8.8-33.4) and memory impairment (17.5%, 95% CI 8.1-29.6). Subgroup analysis showed that participants with a higher risk of long-term sequelae were older, mostly male, living in a high-income country, with more severe status at acute infection. Individuals with severe infection suffered more from PTSD, sleep disturbance, cognitive deficits, concentration impairment, and gustatory dysfunction. Survivors with mild infection had high burden of anxiety and memory impairment after recovery. Our findings suggest that after recovery from acute COVID-19, half of survivors still have a high burden of either physical or mental sequelae up to at least 12 months. It is important to provide urgent and appropriate prevention and intervention management to preclude persistent or emerging long-term sequelae and to promote the physical and psychiatric wellbeing of COVID-19 survivors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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•This review provides a comprehensive overview of fluorescent chemosensors for copper(II) ion.•Three main types, namely, “on-off”, “off-on” and ratiometric fluorescence chemosensors ...for copper(II) ion are discussed systemically.•Cu2+-promoted reaction based chemosensors are summarized briefly.
Among the transition metal ions, copper is the third most abundant essential trace metal element in human body, and is also required by many living organisms for normal physiological processes, while excessive levels of Cu2+ are highly toxic to organisms and generate enormous quantities of pollution to our living environment. It is an essential and key issue to devise more sensitive and selective fluorescent chemosensors to efficiently evaluate the Cu2+ levels in environmental and biological systems. This review summarizes the important advances in fluorescent chemosensors for Cu2+, mainly made in the recent five years. Three types of chemosensors, namely ‘on-off’, ‘off-on’ and ‘ratiometric’, are categorized according to fluorescence signal changes, and each type is further classified into several sections according to the molecular structure features and/or recognition mechanisms. Additionally, the Cu2+-promoted reaction based chemosensors are also discussed by the different reactions like hydrolysis, oxidation and reduction. The molecular structures, recognition mechanism and applications of the fluorescent chemosensors are emphatically discussed, and the future perspective is overviewed briefly.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A highly enantioselective iridium‐ or ruthenium‐catalyzed intermolecular reductive amination/asymmetric hydrogenation relay with 2‐quinoline aldehydes and aromatic amines has been developed. A broad ...range of sterically tunable chiral N,N′‐diaryl vicinal diamines were obtained in high yields (up to 95 %) with excellent enantioselectivity (up to >99 % ee). The resulting chiral diamines could be readily transformed into sterically hindered chiral N‐heterocyclic carbene (NHC) precursors, which are otherwise difficult to access. The usefulness of this synthetic approach was further demonstrated by the successful application of one of the chiral vicinal diamines and chiral NHC ligands in a transition‐metal‐catalyzed asymmetric Suzuki–Miyaura cross‐coupling reaction and asymmetric ring‐opening cross‐metathesis, respectively.
In tandem: A direct and atom‐economical synthesis of enantiomerically enriched vicinal diamines by the title iridium‐ or ruthenium‐catalyzed reaction of 2‐quinoline aldehydes and aromatic amines is described (see scheme). The sterically tunable chiral diamine products provided a platform for the synthesis of bulky chiral NHC ligands and can themselves serve as ligands for asymmetric transition‐metal catalysis. IPA=isopropanol.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Neutral eosin Y‐derived photoexcited states have been found to serve as photoacids and direct hydrogen atom transfer (HAT) catalysts in the activation of glycals and C−H bonds, respectively. These ...studies pave the way for further use of eosin Y in photochemical synthesis.
New sides of eosin Y: Neutral eosin Y‐derived photoexcited states have been found to serve as photoacids and direct hydrogen atom transfer (HAT) catalysts in the activation of glycals and C−H bonds, respectively. These studies pave the way for further use of eosin Y in photochemical synthesis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aim: The etiology of hypertension is various and complex, involving both genetic and behavioral factors. The relationship between psychosocial stress and hypertension has been hypothesized. More and ...more people experience increased anxiety, depression, and chronic psychosocial stress brought on by globalization, cultural changes, socioeconomic changes, and stress at the work place. Although a plethora of studies have investigated the interaction between psychosocial stress and hypertension, this relationship is still contentious. The objective of this study is twofold. First, a review of recent advancements in our understanding of the relationship between psychosocial stress and hypertension. Second, a meta-analysis aiming to assess the relationship between chronic psychosocial stress and blood pressure.
Methods: We systematically searched and identified relevant studies from five databases, including PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), CQVIP, and the Wanfang Database until April 2016. Eleven studies encompassing 5696 participants were included in the final analysis.
Results: Data showed that psychosocial stress was associated with an increased risk of hypertension (OR = 2.40, 95% CI = 1.65-3.49), and hypertensive patients had a higher incidence of psychosocial stress compared to normotension patients (OR = 2.69, 95% CI = 2.32-3.11). Based on our meta-analysis, chronic psychosocial stress may be a risk factor for hypertension.
Conclusion: The few cohort and case-control studies on the association between psychosocial stress and hypertension employed variable definition of stressors and the responses, making the meta-analysis difficult. Although we found an association between chronic psychosocial stress and hypertension, more studies are needed to confirm this relationship.
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