PROTACs targeting androgen receptor signaling: Potential therapeutic agents for castration-resistant prostate cancer.

After the initial androgen deprivation therapy (ADT), part of the prostate cancer may continuously deteriorate into castration-resistant prostate cancer (CRPC). The majority of patients suffer from the localized illness at primary diagnosis that could rapidly assault other organs. This disease stage is referred as metastatic castration-resistant prostate cancer (mCRPC). Surgery and radiation are still the treatment of CRPC, but have some adverse effects such as urinary symptoms and sexual dysfunction. Hormonal castration therapy interfering androgen receptor (AR) signaling pathway is indispensable for most advanced prostate cancer patients, and the first- and second-generation of novel AR inhibitors could effectively cure hormone sensitive prostate cancer (HSPC). However, the resistance to these chemical agents is inevitable, so many of patients may experience relapses. The resistance to AR inhibitor mainly involves AR mutation, splice variant formation and amplification, which indicates the important role in CRPC. Proteolysis-targeting chimera (PROTAC), a potent technique to degrade targeted protein, has recently undergone extensive development as a biological tool and therapeutic drug. This technique has the potential to become the next generation of antitumor therapeutics as it could overcome the shortcomings of conventional small molecule inhibitors. In this review, we summarize the molecular mechanisms on PROTACs targeting AR signaling for CRPC, hoping to provide insights into drug development and clinical medication.

The Impact of Adjuvant Chemotherapy on the Long-Term Prognosis of Breast Malignant Phyllodes Tumors: A Propensity Score-Matched Study.

BACKGROUND: Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. PATIENTS AND METHODS: Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence-free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. RESULTS: We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). CONCLUSIONS: According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.

Food insecurity is related to eating disorder psychopathology beyond psychological distress in rural Chinese adolescents.

OBJECTIVE: This study aimed to examine the relationship between food insecurity (FI) and eating disorder psychopathology in a large sample of rural Chinese adolescents. METHODS: Analyses included 1654 adolescents (55.4% girls; Mage = 16.54 years, SD = 1.45) from a rural high school in southwestern China. FI, eating disorder psychopathology, and psychological distress (i.e., symptoms of depression, anxiety, and stress) were assessed. Data were analyzed by sex. Pearson correlation analysis was performed to investigate the zero-order association between FI and eating disorder psychopathology. Hierarchical linear regressions were used to explore whether FI could explain meaningful variance in eating disorder psychopathology beyond psychological distress and demographic covariates (e.g., socioeconomic status). RESULTS: FI was significantly associated with higher eating disorder psychopathology for boys (r = 0.44, p < 0.001) and girls (r = 0.43, p < 0.001), with medium-to-large effect sizes. FI accounted for significant unique variance in eating disorder psychopathology beyond psychological distress and demographic covariates for boys (ΔR2 = 0.14, p < 0.001) and girls (ΔR2 = 0.10, p < 0.001). DISCUSSION: Using a large sample of rural Chinese adolescents, this study extends the connection between FI and eating disorder pathology in adolescents beyond the Western context. Future investigations on the mechanisms underlying FI and eating disorder psychopathology are warranted for developing prevention strategies for eating disorders among rural Chinese adolescents. PUBLIC SIGNIFICANCE: This is the first investigation that examined the link between FI and eating disorder psychopathology among rural Chinese adolescents. Our findings highlight the importance of incorporating FI as a potential risk factor to screen for the prevention and intervention of eating disorders among rural Chinese adolescents.

CNN and Attention-Based Joint Source Channel Coding for Semantic Communications in WSNs.

Wireless Sensor Networks (WSNs) have emerged as an efficient solution for numerous real-time applications, attributable to their compactness, cost-effectiveness, and ease of deployment. The rapid advancement of 5G technology and mobile edge computing (MEC) in recent years has catalyzed the transition towards large-scale deployment of WSN devices. However, the resulting data proliferation and the dynamics of communication environments introduce new challenges for WSN communication: (1) ensuring robust communication in adverse environments and (2) effectively alleviating bandwidth pressure from massive data transmission. In response to the aforementioned challenges, this paper proposes a semantic communication solution. Specifically, considering the limited computational and storage resources of WSN devices, we propose a flexible Attention-based Adaptive Coding (AAC) module. This module integrates window and channel attention mechanisms, dynamically adjusts semantic information in response to the current channel state, and facilitates adaptation of a single model across various Signal-to-Noise Ratio (SNR) environments. Furthermore, to validate the effectiveness of this approach, the paper introduces an end-to-end Joint Source Channel Coding (JSCC) scheme for image semantic communication, employing the AAC module. Experimental results demonstrate that the proposed scheme surpasses existing deep JSCC schemes across datasets of varying resolutions; furthermore, they validate the efficacy of the proposed AAC module, which is capable of dynamically adjusting critical information according to the current channel state. This enables the model to be trained over a range of SNRs and obtain better results.

PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer progression via activating NF-κB signaling pathway.

Pyruvate dehydrogenase kinase 1 (PDK1) is a widely known glycolytic enzyme, and some evidence showed that PDK1 promoted breast cancer by multiple approaches. However, very few lncRNAs have been identified to be associated with PDK1 in breast cancer in previous research. In this study, we found that lncRNA sprouty4-intron transcript 1 (SPRY4-IT1) was regulated by PDK1 with correlation analysis, and PDK1 upregulated SPRY4-IT1 remarkably in breast cancer cells, as PDK1 interacted with SPRY4-IT1 in the nucleus and significantly enhanced the stability of SRPY4-IT1. Furthermore, SPRY4-IT1 was highly expressed in breast cancer, significantly promoted the proliferation and inhibited apoptosis of breast cancer cells. In terms of mechanism, SPRY4-IT1 inhibited the transcription of NFKBIA and the expression of IκBα, thus promoting the formation of p50/p65 complex and activating NF-κB signaling pathway, which facilitated survival of breast cancer cells. Therefore, our finding reveals that PDK1/SPRY4-IT1/NFKBIA axis plays a crucial role that promoting tumor progression, and SPRY4-IT1 knockdown incombined with PDK1 inhibitor is promising to be a new therapeutic strategy in breast cancer.

Cell-Penetrating Peptide Conjugated Au Nanoclusters Selectively Suppress Refractory Lymphoma Cells via Targeting Both Canonical and Noncanonical NF-κB Signaling Pathways.

Activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is the most aggressive form of DLBCL, with a significantly inferior prognosis due to resistance to the standard R-CHOP immunochemotherapy. Survival of ABC-DLBCL cells addicted to the constitutive activations of both canonical and noncanonical NF-κB signaling makes them attractive therapeutic targets. However, a pharmaceutical approach simultaneously targeting the canonical and noncanonical NF-κB pathway in the ABC-DLBCL cell is still lacking. Peptide-conjugated gold nanoclusters (AuNCs) have emerged unique intrinsic biomedical activities and possess a great potential in cancer theranostics. Here, we demonstrated a Au25 nanocluster conjugated by cell-penetrating peptides that can selectively repress the growth of ABC-DLBCL cells by inducing efficient apoptosis, more efficiently than glutathione (GSH)-conjugated AuNCs. The mechanism study showed that the cell-penetrating peptides enhanced the cellular internalization efficiency of AuNCs, and the selective repression in ABC-DLBCL cells is due to the inhibition of inherent constitutive canonical and noncanonical NF-κB activities by AuNCs. Several NF-κB target genes involved in chemotherapy resistance in ABC-DLBCL cells, including anti-apoptotic Bcl-2 family members and DNA damage repair proteins, were effectively down-regulated by the AuNC. The emerged novel activity of AuNCs in targeting both arms of NF-κB signaling in ABC-DLBCL cells may provide a promising candidate and a new insight into the rational design of peptide-conjugated Au nanomedicine for molecular targeting treatment of refractory lymphomas.

The elicitation of affordance depends on conceptual attributes: evidence from a virtual reality study.

Affordance is a property of object with respect to the observer, which is related to the attributes of the object. In the present study, we examined whether affordance elicitation is primarily based on the conceptual attributes or instance attributes of the object. To distinguish the role of the two types of attributes in elicitation of affordance, we manipulated the size of a pan in virtual reality (Experiment 1). The critical condition is the giant pan, which should elicit manipulability affordance if affordance is concept-based and it should not elicit manipulability affordance if affordance is instance-based. The results support the former assumption, i.e., the elicitation of affordance is concept-based. To confirm the conclusion, we created a water-handled pan in virtual reality and examined its manipulability affordance (Experiment 2). The water-handled pan looks similar to a normal pan, but its handle is composed of flowing water which, in concept, cannot be grasped. Consistent with the concept-based conclusion, the water-handled pan did not elicit manipulability affordance. The present findings provided convergent evidence that ordinary people rely primarily on conceptual attributes of the object to elicit manipulability affordance.

The role and molecular mechanism of metabolic reprogramming of colorectal cancer by UBR5 through PYK2 regulation of OXPHOS expression study.

Colorectal carcinoma (CRC) is the third most malignant tumor in the world, but the key mechanisms of CRC progression have not been confirmed. UBR5 and PYK2 expression levels were detected by RT-qPCR. The levels of UBR5, PYK2, and mitochondrial oxidative phosphorylation (OXPHOS) complexes were detected by western blot analysis. Flow cytometry was used to detect ROS activity. The CCK-8 assay was used to assess cell proliferation and viability. The interaction between UBR5 and PYK2 was detected by immunoprecipitation. A clone formation assay was used to determine the cell clone formation rate. The ATP level and lactate production of each group of cells were detected by the kit. EdU staining was performed for cell proliferation.Transwell assay was performed for cell migration ability. For the CRC nude mouse model, we also observed and recorded the volume and mass of tumor-forming tumors. The expression of UBR5 and PYK2 was elevated in both CRC and human colonic mucosal epithelial cell lines, and knockdown of UBR5 had inhibitory effects on cancer cell proliferation and cloning and other behaviors in the CRC process by knockdown of UBR5 to downregulate the expression of PYK2, thus inhibiting the OXPHOS process in CRC; rotenone (OXPHOS inhibitor) treatment enhanced all these inhibitory effects. Knockdown of UBR5 can reduce the expression level of PYK2, thus downregulating the OXPHOS process in CRC cell lines and inhibiting the CRC metabolic reprogramming process.

The association of high-fluoride and high-iodine combined exposure with dental fluorosis and goiter: a meta-analysis.

It is controversial that high-fluoride and high-iodine combined exposure affects the prevalence of dental fluorosis and goiter. The aim of this study was to explore the potential association between high-fluoride and high-iodine combined exposure with dental fluorosis and goiter. We retrieved relevant articles from PubMed, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database and China Science and Technology Journal Database (VIP). The query format was 1 # "Fluorosis" OR "Fluoride," 2 # "Iodine" OR "Iodide," and 3 # 1 AND 2. A total of 20 papers were included in this study after independent review by two investigators. Our analysis showed that high-fluoride and high-iodine biphasic exposure was significantly associated with the prevalence of goiter (OR = 4.69, 95% CI 2.82-7.80, P < 0.001). The prevalence of dental fluorosis was also significantly raised (OR = 11.71, 95% CI 7.57-18.14, P < 0.001). Sensitivity analysis suggested that combined statistics of multiple studies were reliable. For goiter, subgroup analysis revealed study province, sample size and published year as sources of heterogeneity (P < 0.001). For dental fluorosis, only sample size was the impact factor of heterogeneity. As well, funnel plot, Begg's test and Egger's test suggested there was no publication bias (P > 0.05). Overall, our study demonstrates that high-fluoride and high-iodine combined exposure is a risk factor for occurrence of dental fluorosis and goiter. The chronic of high-fluoride and high-iodine combined exposure is a significant higher risk of disease than normal.

Natural essential oils efficacious in internal organs fibrosis treatment: Mechanisms of action and application perspectives.

Internal organs fibrosis (IOF) is the leading cause of morbidity and mortality in most chronic inflammatory diseases, which is responsible for 45% of deaths due to disease. However, there is a paucity of drugs used to treat IOF, making it urgent to find medicine with good efficacy, low toxic side effects and good prognosis. Essential oils (EOs) extracted from natural herbs with a wide range of pharmacological components, multiple therapeutic targets, low toxicity, and broad sources have unique advantages and great potential in the treatment of IOF. In this review, we summarized EOs and their monomeric components with anti-IOF, and found that they work mainly through inhibiting TGF-ß-related signaling pathways, modulating inflammatory cytokines, suppressing NF-κB, and anti-oxidative stress. The prognostic improvement of natural EOs on IOF was further discussed, as well as the quality and safety issues in the current development of natural EOs. This review hopes to provide scientific basis and new ideas for the development and application of natural medicine EOs in anti-IOF.

Macrophage membrane modified baicalin liposomes improve brain targeting for alleviating cerebral ischemia reperfusion injury.

Baicalin (BA) has a good intervention effect on encephalopathy. In this study, macrophage membrane was modified on the surface of baicalin liposomes (BA-LP) by extrusion method. Macrophage membrane modified BA-LP (MM-BA-LP) was characterized by various analytical techniques, and evaluated for brain targeting. The results presented MM-BA-LP had better brain targeting compared with BA-LP. Pharmacokinetic experiments showed that MM-BA-LP improved pharmacokinetic parameters and increased the residence time of BA. Pharmacodynamic of middle cerebral artery occlusion (MCAO) rat model was studied to verify the therapeutic effect of MM-BA-LP on cerebral ischemia reperfusion injury (CIRI). The results showed that MM-BA-LP could significantly improve the neurological deficit, cerebral infarction volume and brain pathological state of MCAO rats compared with BA-LP. These results suggested that MM-BA-LP could significantly enhance the brain targeting and improve the circulation of BA in blood, and had a significantly better neuroprotective effect on MCAO rats than BA-LP.

Borneol in cardio-cerebrovascular diseases: Pharmacological actions, mechanisms, and therapeutics.

With the coming acceleration of global population aging, the incidence rate of cardio-cerebrovascular diseases (CVDs) is increasing. It has become the leading cause of human mortality. As a natural drug, borneol (BO) not only has anti-inflammatory, anti-oxidant, anti-apoptotic, anti-coagulant activities and improves energy metabolism but can also promote drugs to enter the target organs or tissues through various physiological barriers, such as the blood-brain barrier (BBB), mucous membrane, skin. Thus, it has a significant therapeutic effect on various CVDs, which has been confirmed in a large number of studies. However, the pharmacological actions and mechanisms of BO on CVDs have not been fully investigated. Hence, this review summarizes the pharmacological actions and possible mechanisms of BO, which provides novel ideas for the treatment of CVDs.

Natural volatile oils derived from herbal medicines: A promising therapy way for treating depressive disorder.

Depression is a common global mental disorder that seriously harms human physical and mental health. With the development of society, the increase of pressure and the role of various other factors make the incidence of depression increase year by year. However, there is a lack of drugs that have a fast onset, significant effects, and few side effects. Some volatile oils from traditional natural herbal medicines are usually used to relieve depression and calm emotions, such as Lavender essential oil and Acorus tatarinowii essential oil. It was reported that these volatile oils, are easy to enter the brain through the blood-brain barrier and have good antidepressant effects with little toxicity and side effects. In this review, we summarized the classification of depression, and listed the history of using volatile oils to fight depression in some countries. Importantly, we summarized the anti-depressant natural volatile oils and their monomers from herbal medicine, discussed the anti-depressive mechanisms of the volatile oils from natural medicine. The volatile oils of natural medicine and antidepressant drugs were compared and analyzed, and the application of volatile oils was explained from the clinical use and administration routes. This review would be helpful for the development of potential anti-depressant medicine and provide new alternative treatments for depressive disorders.

Feasibility and efficacy of microwave ablation for treating breast fibroadenoma.

BACKGROUND: To investigate the safety, efficacy, and follow-up outcomes of microwave ablation (MWA) in patients with breast fibroadenoma. METHODS: An institutional review board-approved this study of patients treated with MWA for breast fibroadenoma from October 2017 to March 2019. Clinical features of patients and breast fibroadenoma were analyzed. At follow-up all patients received physical examination and ultrasound imaging. RESULTS: In total, 171 patients with 271 lesions were enrolled. The mean lesion diameter was 1.35 ± 0.47 cm. The results revealed differential lesion states, including stability, enlargement, reduction, and complete regression, at 1-6, 6-12, and >12 months of follow-up. The size was reduced in 22.14% (31/140), 26.36% (29/110), and 36.36% (16/44) of the lesions at 1-6, 6-12, and >12 months of follow-up, respectively. The proportion of lesions with complete regression was 24.29% (34/140) at 1-6 months, 45.45% (50/110) at 6-12 months, and 40.91% (18/44) at >12 months of follow up. There was no significant relationship between the curative effect and age, lesion location, and blood flow in patients with breast fibroadenoma after MWA (p > .05), but there was statistically significant relationship with lesion diameter (categorized as <1.5 cm and ≥1.5 cm) (p < .05). CONCLUSIONS: The current evidence indicates that MWA is a safe and effective method for treating breast fibroadenoma. Nevertheless, further large-scale prospective trials and well-designed future studies are warranted to validate our findings.

Geniposide-Loaded Liposomes for Brain Targeting: Development, Evaluation, and In Vivo Studies.

Geniposide (GE) possesses excellent neuroprotective effects but with poor brain targeting and short half-life. Liposome was considered to have great potential for brain diseases. Therefore, this research aimed to develop a geniposide liposome (GE-LP) as a brain delivery system for cerebral ischemia reperfusion injury (CIRI) therapy and evaluate its characterization, pharmacokinetics, brain targeting, and neuroprotective effects in vivo. Then, a reverse-phase evaporation method was applied to develop the GE-LP and optimize the formulation. Notably, the GE-LP had suitable size, which was 223.8 nm. Subsequently, the pharmacokinetic behavior of GE solution and GE-LP in mice plasma was investigated, and the brain targeting was also researched. The results showed that GE in plasma of GE-LP displayed three folds longer distribution half-life and a higher bioavailability and brain targeting compared to GE solution. In vivo neuroprotective effects was evaluated through the middle cerebral artery occlusion (MCAO) rat model, and GE-LP exhibited a stronger tendency in preventing the injury of CIRI, which can significantly improve neurological deficits. Overall, this study demonstrates GE-LP as a new formulation with ease of preparation, sustained release, and high brain targeting, which has significant development prospects on CIRI; this is expected to improve the efficacy of GE and reduce the frequency of administration.

[Detection method of nonlinear magnetized harmonic signal of medical magnetic nanoparticles].

Medical magnetic nanoparticles are nano-medical materials with superparamagnetism, which can be collected in the tumor tissue through blood circulation, and magnetic particle imaging technology can be used to visualize the concentration of magnetic nanoparticles in the living body to achieve the purpose of tumor imaging. Based on the nonlinear magnetization characteristics of magnetic particles and the frequency characteristics of their magnetization, a differential detection method for the third harmonic of magnetic particle detection signals is proposed. It was modeled and analyzed, to study the nonlinear magnetization response characteristics of magnetic particles under alternating field, and the spectral characteristics of magnetic particle signals. At the same time, the relationship between each harmonic and the amount of medical magnetic nanoparticle samples was studied. On this basis, a signal detection experimental system was built to analyze the spectral characteristics and power spectral density of the detected signal, and to study the relationship between the signal and the excitation frequency. The signal detection experiment was carried out by the above method. The experimental results showed that under the alternating excitation field, the medical magnetic nanoparticles would generate a spike signal higher than the background sensing signal, and the magnetic particle signal existed in the odd harmonics of the detected signal spectrum. And the spectral energy was concentrated at the third harmonic, that is, the third harmonic magnetic particle signal detection that meets the medical detection requirement could be realized. In addition, the relationship between each harmonic and the particle sample volume had a positive growth relationship, and the detected medical magnetic nanoparticle sample volume could be determined according to the relationship. At the same time, the selection of the excitation frequency was limited by the sensitivity of the system, and the detection peak of the third harmonic of the detection signal was reached at the excitation frequency of 1 kHz. It provides theoretical and technical support for the detection of medical magnetic nanoparticle imaging signals in magnetic particle imaging research.

Programmable Synthesis of Multimetallic Phosphide Nanorods Mediated by Core/Shell Structure Formation and Conversion.

Generalized synthetic strategies for nanostructures with well-defined physical dimensions and broad-range chemical compositions are at the frontier of advanced nanomaterials design, functionalization, and application. Here, we report a composition-programmable synthesis of multimetallic phosphide CoMPx nanorods (NRs) wherein M can be controlled to be Fe, Ni, Mn, Cu, and their binary combinations. Forming Co2P/MPx core/shell NRs and subsequently converting them into CoMPx solid-solution NRs through thermal post-treatment are essential to overcome the obstacle of morphology/structure inconsistency faced in conventional synthesis of CoMPx with the different M compositions. The resultant CoMPx with uniform one-dimensional (1-D) structure provides us a platform to unambiguously screen the M synergistic effects in improving the electrocatalytic activity, as exemplified by the oxygen evolution reaction. This new approach mediated by core/shell nanostructure formation and conversion can be extended to other multicomponent nanocrystal systems (metal alloy, mixed oxide, and chalcogenide, etc.) for diverse applications.

A multimode, broadband and all-inkjet-printed absorber using characteristic mode analysis.

In this paper, we demonstrate a multimode and broadband absorber that is fabricated directly on PET substrate using a commercial direct-to-garment (DTG) inkjet printer. A design procedure of this kind of absorber is presented. Based on the theory of characteristic mode, the underlying modal behaviors of the absorber structure are firstly analyzed to guide the design of multimode absorber. Two modes on the absorber structure are designed to resonate around 1.83 GHz and 4.28 GHz to cover the working frequency range. Simulation and measurement results show that the multimode absorber with a total thickness of 0.0883λL at the lowest operating frequency can achieve broadband microwave absorption with efficiency over 90% in the frequency band of 1.0 ∼ 4.5 GHz (127.3% in fractional bandwidth) through deliberate design. Both the simulated and experimental results demonstrate the validity of the proposed method and indicate that the method can be applied to other microwave and millimeter-wave regions.

Nose to brain drug delivery - A promising strategy for active components from herbal medicine for treating cerebral ischemia reperfusion.

Cerebral ischemia reperfusion injury (CIRI), one of the major causes of death from stroke in the world, not only causes tremendous damage to human health, but also brings heavy economic burden to society. Current available treatments for CIRI, including mechanical therapies and drug therapies, are often accompanied by significant side-effects. Therefore, it is necessary to discovery new strategies for treating CIRI. Many studies have confirmed that the herbal medicine has the advantages of abundant resources, good curative effect and little side effects, which can be used as potential drug for treatment of CIRI through multiple targets. It's known that oral administration commonly has low bioavailability, and injection administration is inconvenient and unsafe. Many drugs can't delivery to brain through routine pathways due to the blood-brain-barrier (BBB). Interestingly, increasing evidences have suggested the nasal administration is a potential direct route to transport drug into brain avoiding the BBB and has the characteristics of high bioavailability for treating brain diseases. Therefore, intranasal administration can be treated as an alternative way to treat brain diseases. In the present review, effective methods to treat CIRI by using active ingredients derived from herbal medicine through nose to brain drug delivery (NBDD) are updated and discussed, and some related pharmacological mechanisms have also been emphasized. Our present study would be beneficial for the further drug development of natural agents from herbal medicines via NBDD.

Baicalin Liposome Alleviates Lipopolysaccharide-Induced Acute Lung Injury in Mice via Inhibiting TLR4/JNK/ERK/NF-κB Pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are challenging diseases with the high mortality in a clinical setting. Baicalin (BA) is the main effective constituent isolated from the Chinese medical herb Scutellaria baicalensis Georgi, and studies have proved that it has a protective effect on ALI induced by lipopolysaccharide (LPS) due to the anti-inflammatory efficacy. However, BA has low solubility which may limit its clinical application. Hence, we prepared a novel drug delivery system-Baicalin liposome (BA-LP) in previous research-which can improve some physical properties of BA. Therefore, we aimed to explore the effect of BA-LP on ALI mice induced by LPS. In pharmacokinetics study, the values of t 1/2 and AUC0- t in the BA-LP group were significantly higher than that of the BA group in normal mice, indicating that BA-LP could prolong the duration time in vivo of BA. The BA-LP group also showed a higher concentration in lung tissues than the BA group. Pharmacodynamics studies showed that BA-LP had a better effect than the BA group at the same dosage on reducing the W/D ratio, alleviating the lung injury score, and decreasing the proinflammatory factors (TNF-α, IL-1ß) and total proteins in bronchoalveolar lavage fluids (BALF). In addition, the therapeutic effects of BA-LP showed a dose-dependent manner. Western blot analysis indicated that the anti-inflammatory action of BA could be attributed to the inhibition of the TLR4-NFκBp65 and JNK-ERK signaling pathways. These results suggest that BA-LP could be a valuable therapeutic candidate in the treatment of ALI.