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•Association of household fuel use and cognitive functioning in older Chinese people.•Orientation/attention, episodic memory, and visuo-construction based questionnaire.•Solid ...cooking, heating, and combined fuel use was associated with cognitive decline.•Change from solid to clean cooking fuel showed lower cognitive decline over 4 years.
To date, few studies have focused on the influence of indoor air pollution on cognitive impairment. Thus, we aimed to explore the association of household fuel use, the major cause of household air pollution, with cognitive functioning among a sample of middle-aged and older Chinese individuals.
A total of 10,372 and 8,397 participants from the China Health and Retirement Longitudinal Study (CHARLS) were enrolled in the cross-sectional and follow-up analyses, respectively. Cognitive functioning was evaluated via a structured questionnaire in three dimensions: orientation and attention, episodic memory, and visuo-construction. The associations between household solid fuel use (for cooking and heating) and cognitive functioning were elucidated by generalized linear models. Furthermore, we explored the combined effect of solid fuel use in cooking and heating and examined the effects of switching cooking fuel types on a 4-year change in cognitive functioning.
In the cross-sectional study, solid fuel use for cooking or heating, separately or simultaneously, was positively associated with cognitive impairment, after adjusting for potential confounders. Similarly, in the follow-up study, solid cooking fuel use was associated with a greater decline in cognitive score overall (β = −0.24, 95% confidence interval CI: −0.45, −0.04), mostly in the episodic memory (β = −0.19, 95% CI: −0.34, −0.03) and visuo-construction (β = −0.03, 95% CI: −0.05, −0.01) dimensions; solid heating fuel use was associated only with a greater decrease in the orientation and attention dimension (β = −0.13, 95% CI: −0.25, −0.01). A combined effect of household fuel use was also observed (P < 0.05). Moreover, subjects who switched from solid to cleaner cooking fuel displayed a significantly lower degree of cognitive decline for all dimensions than did persistent solid fuel users over a 4-year period (P < 0.05).
Our findings show that household solid fuel use is a risk factor for the development of cognitive impairment. Improving the structure of cooking fuel may therefore have great public health value for the prevention of cognitive impairment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cancer tissues consist of cancer cells, surrounding stromal cells and the extracellular matrix. Cancer‐associated fibroblasts (CAF) are one of the key components of stromal cells. CAF have a great ...impact on the behavior of cancer cells, including proliferation, invasion, metastasis and chemoresistance in many ways. However, the underlying mechanism had not been fully elucidated. In this study, we investigated the role of CAF in cisplatin resistance of lung cancer cells. By using conditioned medium from CAF (CAF‐CM), we found that CAF decreased the sensitivity of lung cancer cells to cisplatin. RNA sequencing results showed that CAF expressed a higher level of Annexin A3 (ANXA3) than normal fibroblasts (NF), and CAF‐CM incubation increased the ANXA3 level in lung cancer cells. Overexpression of ANXA3 in lung cancer cells increased cisplatin resistance and activated c‐jun N‐terminal kinase (JNK), whereas knockdown of ANXA3 increased cisplatin sensitivity. Further study showed that CAF‐CM enhanced cisplatin resistance by inhibiting cisplatin‐induced apoptosis, determined by repression of caspase‐3 and caspase‐8, through activation of the ANXA3/JNK pathway. Conversely, suppression of JNK activation by specific inhibitor retarded the effect of CAF‐CM and ANXA3 on cisplatin sensitivity. Taken together, our study demonstrated that CAF potentiated chemoresistance of lung cancer cells through a novel ANXA3/JNK pathway both in vitro and in vivo, suggesting ANXA3 could be a potential therapeutic target for the treatment of chemoresistant cancer.
Cancer‐associated fibroblasts decreased the sensitivity of lung cancer cells to cisplatin. CAF expressed higher level of ANXA3 than normal fibroblasts (NF), and CAF‐CM incubation increased the ANXA3 level in lung cancer cells. CAF potentiated chemoresistance of lung cancer cells through a novel ANXA3/JNK pathway both in vitro and in vivo.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tumor progression requires the communication between tumor cells and tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are major components of stromal cells. CAFs contribute to ...metastasis process through direct or indirect interaction with tumor cells; however, the underlying mechanism is largely unknown. Here, we reported that autophagy was upregulated in lung cancer-associated CAFs compared to normal fibroblasts (NFs), and autophagy was responsible for the promoting effect of CAFs on non-small cell lung cancer (NSCLC) cell migration and invasion. Inhibition of CAFs autophagy attenuated their regulation on epithelial-mesenchymal transition (EMT) and metastasis-related genes of NSCLC cells. High mobility group box 1 (HMGB1) secreted by CAFs mediated CAFs' effect on lung cancer cell invasion, demonstrated by using recombinant HMGB1, HMGB1 neutralizing antibody, and HMGB1 inhibitor glycyrrhizin (GA). Importantly, the autophagy blockade of CAFs revealed that HMGB1 release was dependent on autophagy. We also found HMGB1 was responsible, at least in part, for autophagy activation of CAFs, suggesting CAFs remain active through an autocrine HMGB1 loop. Further study demonstrated that HMGB1 facilitated lung cancer cell invasion by activating the NFκB pathway. In a mouse xenograft model, the autophagy specific inhibitor chloroquine abolished the stimulating effect of CAFs on tumor growth. These results elucidated an oncogenic function for secretory autophagy in lung cancer-associated CAFs that promotes metastasis potential, and suggested HMGB1 as a novel therapeutic target.
Recent studies indicate that cancer-associated fibroblasts (CAFs) are involved in tumor growth, invasion and metastasis, however, the underling mechanisms remain unclear. In the present study, we ...investigated the role of CAFs on the metastatic potential of lung cancer cells. The stromal fibroblasts we isolated from lung cancer tissues presented CAFs characteristics with high levels of α-smooth muscle actin (α-SMA) and fibroblast-activating protein (FAP). Our data showed that the conditioned medium from cultured CAFs (CAF-CM) dramatically enhanced migration and invasion of lung cancer cells. CAF-CM induced epithelial-mesenchymal transition (EMT) by regulating the expression of EMT-associated markers E-cadherin and vimentin, and also modulated metastasis-related genes MMP-2 and VEGF both
and
. Further mechanistic studies demonstrated that CAFs enhanced the metastatic potential of lung cancer cells by secreting IL-6, subsequently activating of JAK2/STAT3 signaling pathway. Additionally, the inhibition of IL-6/STAT3 signaling pathway by IL-6 neutralizing antibody or specific inhibitors of JAK2/STAT3 reversed CAF-CM induced EMT and migration of lung cancer cells. Taken together, these findings revealed a novel mechanism that CAFs induced EMT and promoted metastasis of lung cancer cells through the IL-6/STAT3 signaling pathway.
Physical limitation, which has been linked to outdoor air pollution exposure in previous studies, is a risk factor for disability and even for premature death. Although people often spend more time ...indoors, the relationship between indoor air pollution and physical function has not been fully explored.
The associations of household fuel types with self-reported and performance-based physical functioning were tested on a total of 12,458 participants in the China Health and Retirement Longitudinal Study (CHARL), using generalized linear models and logistic regression models. Additionally, subgroup analyses according to smoking status and number of chronic diseases, were performed regarding these associations.
Our results revealed that after adjusting for potential confounds, solid fuel use in cooking showed −0.08 (−0.13, −0.04) and −0.15 (−0.23, −0.06) declines in self-reported and performance-based physical functioning scores (higher scores means fewer physical limitations), when compared with cleaner groups, respectively. Considering these outcomes as binary variables, the ORs (95% CIs) for abnormal self-reported and performance-based physical functioning in the solid fuel cooking group were 1.226 (1.053–1.427) and 1.194 (1.072–1.330), respectively. No significant association between heating fuel use and physical functioning was observed. Additionally, no modification effect of smoking status and the number of chronic diseases on the association between cooking fuel use and performance-based physical functioning was observed (P > 0.05).
Our findings suggested that solid cooking fuel use may be associated with self-reported and performance-based physical functioning decline of middle-aged and elder Chinese populations.
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•Association of household fuel use and physical functioning in older Chinese people.•Self-reported and performance-based physical functioning were both measured.•Solid cooking fuel use was associated with self-reported and performance-based physical functioning decline.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hearing loss, a common chronic condition, severely affects the quality of human life. However, the longitudinal relationships between household solid fuel use and hearing loss are unclear. To explore ...the associations between household solid fuel use and hearing loss in a Chinese population. There were 8835 participants enrolled in this prospective cohort study. Hearing function was assessed by asking the following self-reported question. Cox proportional hazards regression models were used to examine the relationships between baseline household solid fuel use and hearing loss incidence. After 6 (range, 2–7) years of follow-up, 1654 (18.72%) of 8835 participants developed hearing loss. This study demonstrated that increasing baseline solid fuel exposure was associated with a higher rate of poor hearing function (P for trend < 0.01). Compared with the clean fuel group (both cooking and heating), the hazard ratios (HR) (95% confidence intervals) of poor hearing function for the solid fuel group (cooking or heating) and both solid fuel groups (both cooking and heating) were 1.17 (1.01, 1.37) and 1.26 (1.09, 1.45) after adjustments, respectively. In subgroup analysis of household energy sources, the use of solid fuels for both heating (HR, 1.21; 1.07, 1.37) and cooking (HR, 1.12; 1.01, 1.26) was related to a higher incidence of poor hearing function. In subgroup analysis of place of residence, more solid fuel use was associated with a higher rate of poor hearing function in urban communities (HR, 1.39; 1.12, 1.74) but not in rural villages (HR, 1.18; 0.97, 1.45). Moreover, compared with the population that used solid fuel for cooking at both baseline and follow-up, those who switched from solid to clean fuel had a lower risk of developing poor hearing function (HR, 0.54, 0.46–0.63). This study demonstrates that household solid fuel use is closely associated with poor hearing function. Programs that educate individuals on the effects of household fuel use on hearing function should be established, especially in urban communities.
•Solid fuel exposure was associated with a higher rate of poor hearing function.•This association was confirmed in urban communities but not in rural villages.•Those who switched from solid to clean fuel had a lower risk of poor hearing function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In clinical practice, it is difficult to identify tumor margins during brain surgery due to its inherent infiltrative character. Herein, a unique dual‐modality nanoprobe (Gd‐DOTA‐Ag2S QDs, referred ...as Gd‐Ag2S nanoprobe) is reported, which integrates advantages of the deep tissue penetration of enhanced magnetic resonance (MR) imaging of Gd and the high signal‐to‐noise ratio and high spatiotemporal resolution of fluorescence imaging in the second near‐infrared window (NIR‐II) of Ag2S quantum dots (QDs). Due to the abundant tumor angiogenesis and the enhanced permeability and retention effect in the tumor, a brain tumor (U87MG) in a mouse model is clearly delineated in situ with the help of the Gd assisted T1 MR imaging and the intraoperative resection of the tumor is precisely accomplished under the guidance of NIR‐II fluorescence imaging of Ag2S QDs after intravenous injection of Gd‐Ag2S nanoprobe. Additionally, no histologic changes are observed in the main organs of the mouse after administration of Gd‐Ag2S nanoprobe for 1 month, indicating the high biocompatibility of the nanoprobe. We expect that such a novel “Detection and Operation” strategy based on Gd‐Ag2S nanoprobe is promising in future clinical applications.
Gd‐Ag2S nanoprobes, which integrate advantages of the deep tissue penetration of enhanced magnetic resonance imaging (MRI) of Gd and the high signal‐to‐noise ratio and high spatiotemporal resolution of fluorescence imaging in the second near‐infrared window (NIR‐II) of Ag2S quantum dots, acts as a new dual‐modality nanoprobe for profiling and imaging‐guided surgery of brain tumor by a “detection and operation” approach.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Phenethyl isothiocyanate (PEITC) is a natural compound abundant in cruciferous vegetables. PEITC possesses anti‐tumor effect in various human malignances. Our previous study has shown that benzyl ...isothiocyanates (BITC) induce autophagy in lung cancer cells. However, whether autophagy play a role in the inhibitory effect of PEITC on lung cancer metastasis is unclear. In this study, we found that PEITC suppressed migration and invasion of lung cancer cells by regulating MMP2. It also induced autophagy, evidenced by the formation of acidic vesicular organelles (AVOs), the punctate pattern of LC3, the accumulation of LC3‐II, and the expression of Beclin‐1. Inhibition of autophagy by 3‐MA and chloroquine (CQ) or knock down of Beclin‐1 enhanced PEITC‐caused metastasis inhibition. JAK2/STAT3 pathway was suppressed by PEITC, and further inhibited by 3‐MA and CQ or Beclin‐1 knock down, as a result of decreased expression of p‐JAK2 and p‐STAT3. Blocking JAK2/STAT3 pathway by inhibitor AG490 and Stattic suppressed cell migration and decreased the expression of MMP2, MMP9, Twist, and c‐Myc. Further in vivo study showed that PEITC inhibited tumor growth, induced autophagy and suppressed JAK2/STAT3 pathway, and inhibitor CQ enhanced this effect. Taken together, our results demonstrate that PEITC inhibits metastasis potential of lung cancer cells, and induces autophagy. The autophagy induced by PEITC preserves metastasis potential of lung cancer cells, via activation of JAK2/STAT3 pathway. Inhibition of autophagy enhanced the inhibitory effect of PEITC on metastasis potential of lung cancer cells. Our finding suggests that targeting autophagy could be a promising strategy for anti‐metastasis therapies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Single-domain antibodies (sdAbs) showed the incredible advantages of small molecular weight, excellent affinity, specificity, and stability compared with traditional IgG antibodies, so their ...potential in binding hidden antigen epitopes and hazard detection in food, agricultural and veterinary fields were gradually explored. Moreover, its low immunogenicity, easy-to-carry target drugs, and penetration of the blood-brain barrier have made sdAbs remarkable achievements in medical treatment, toxin neutralization, and medical imaging. With the continuous development and maturity of modern molecular biology, protein analysis software and database with different algorithms, and next-generation sequencing technology, the unique paratope structure and different antigen binding modes of sdAbs compared with traditional IgG antibodies have aroused the broad interests of researchers with the increased related studies. However, the corresponding related summaries are lacking and needed. Different antigens, especially hapten antigens, show distinct binding modes with sdAbs. So, in this paper, the unique paratope structure of sdAbs, different antigen binding cases, and the current maturation strategy of sdAbs were classified and summarized. We hope this review lays a theoretical foundation to elucidate the antigen-binding mechanism of sdAbs and broaden the further application of sdAbs.
Most lung cancer patients die of metastasis. Recent studies have indicated that dysregulated microRNAs (miRNAs) are involved not only in tumorigenesis, but also in metastasis. In the present study, ...we found that over-expression of miR-26a-5p potentiated the migration and invasion of lung cancer cells evidenced by wound healing assay and transwell assay, and metastasis-related genes MMP-9 and CD44 were up-regulated. We identified integrin-beta8 (ITGβ8) as a novel target of miR-26a, and ITGβ8 expression was negatively correlated with miR-26a-5p expression in lung cancer specimens. Mechanism study showed that miR-26a-5p enhanced lung cancer cell metastasis via activation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, and ITGβ8 mediated the activation of JAK2/STAT3 pathway by miR-26a-5p. By using in vivo imaging technology, we found that miR-26a-5p enhanced both tumor growth and metastasis in vivo; and activated JAK2/STAT3 pathway. Taken together, our results demonstrated that miR-26a-5p potentiated lung cancer cell metastasis via JAK2/STAT3 pathway by targeting ITGβ8. This finding provides insights into the mechanism underlying miRNAs regulation on lung cancer metastasis; and suggests miR-26a-5p as a therapeutic target for lung cancer treatment.
•90% of lung cancer patients die of metastasis.•miR-26a-5p enhances metastasis potential of lung cancer both in vitro and in vivo.•ITGβ8 is identified as a novel target of miR-26a-5p.•miR-26a-5p enhances lung cancer cell metastasis via activation of JAK2/STAT3 pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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