Smoker patients with non-small cell lung cancer (NSCLC) have poorer prognosis and survival than those without smoking history. However, the mechanisms underlying the low response rate of those patients to EGFR tyrosine kinase inhibitors (TKIs) are not well understood. Here we report that exposure to cigarette smoke extract enhances glycolysis and attenuates AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR; this in turn reduces the sensitivity of NSCLC cells with wild-type EGFR (EGFRWT) to EGFR TKI by repressing expression of liver kinase B1 (LKB1), a master kinase of the AMPK subfamily, via CpG island methylation. In addition, LKB1 expression is correlated positively with sensitivity to TKI in patients with NSCLC. Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFRWT and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFRWT.

Natural products are favored because of their non-toxicity, low irritants, and market reacceptance. We collected examples, according to ancient wisdom, of natural products to be applied in transdermal delivery. A transdermal delivery system, including different types of agents, such as ointments, patches, and gels, has long been used for skin concerns. In recent years, many novel transdermal applications, such as nanoemulsions, liposomes, lipid nanoparticles, and microneedles, have been reported. Nanosized drug delivery systems are widely applied in natural product deliveries. Nanosized materials notably enhance bioavailability and solubility, and are reported to improve the transdermal permeation of many substances compared with conventional topical formulations. Natural products have been made into nanosized biomaterials in order to enhance the penetration effect. Before introducing the novel transdermal applications of natural products, we present traditional methods within this article. The descriptions of novel transdermal applications are classified into three parts: liposomes, emulsions, and lipid nanoparticles. Each section describes cases that are related to promising natural product transdermal use. Finally, we summarize the outcomes of various studies on novel transdermal agents applied to skin treatments.

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Background “Jinchuang ointment” is a traditional Chinese herbal medicine for external incised wounds. This herbal medicine has been successfully used to treat patients with diabetic foot ulcers and pressure sores in Taiwan for several decades. We previously examined its biological activities on cell-based in vitro assay platforms. Because some patients refused to use animal-derived ingredients ointment during our clinical practice, the efficacy of plant oil-based reconstituted “Jinchuang ointment” was also investigated. Methods A porcine excisional wound model was established and used to evaluate its efficacy in vivo in this study. Besides, an unusual clinical case is also present. Results As judged from the wound appearance of animal studies on day 14 and the results of blood flow flux at the wound sites on day 28, “Jinchuang ointment” accelerated wound closure significantly better than the control group. Conclusions The results from clinical treatment, histopathological evaluation, and the animal study showed that “Jinchung ointment” promotes wound healing significantly better than the control group. Also, sesame oil-reconstituted ointment can be a choice for patients who refuse to use lard-containing ointment.

Although dual EGFR/HER2 tyrosine kinase inhibitor lapatinib has provided effective clinical benefits for HER2-positive breast cancer patients, acquired resistance to this drug remains a major concern. Thus, the development of alternative therapeutic strategies is urgently needed for patients who failed lapatinib treatment. Proteasome inhibitors have been reported to possess high anti-tumor activity to breast cancer cells. Therefore, this study aims to examine whether and how proteasome inhibitor bortezomib can overcome lapatinib resistance. Treatments with several proteasome inhibitors, including Bortezomib, MG132, and proteasome inhibitor I (PSI), as well as the viabilities of both HER2-positive breast cancer cell lines and their lapatinib-resistant clones, were inhibited. Importantly, the expressions of ErbB family were downregulated at both transcriptional and translational levels. Also, our results further indicated that proteasome inhibitors decreased ErbB family expression through lysosomal degradation pathway in a heat shock protein 90 (HSP90)-dependent manner. In this study, our data supported a potential approach to overcome the acquired resistance of HER2-overexpressing breast cancer patients to lapatinib using proteasome inhibitors.

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Skin, the largest and outermost organ of the body, mainly consisted dermis and epidermis, which provide a barrier function to protect the body from external stimuli and to prevent the loss of moisture from the body. [1][2][3][4] Skin and skin-related diseases, causing a global health burden, have become an international health issues whereas the inflammatory skin diseases were the most common problem in dermatology. The skin inflammation was usually accompanied with erythema and edema in the affected skin area, 5 and tissue destruction could even occur in chronic skin inflammation. 6 The skin inflammation, like erythema and edema, was usually and clinically evaluated by physician's naked-eye first, and such subjective evaluation was very dependent on their experience. Patient epidermal tissue section test, that is, skin biopsy test, might sometimes be required. Although the skin biopsy was still the gold standard for most dermatological diagnosis, it was invasive, and thereby leading to pain and scar

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