Chrysophanol alleviates acute lung injury caused by Klebsiella pneumoniae infection by inhibiting pro-inflammatory cytokine production.

Acute lung injury (ALI) caused by acute bacterial infection remains a common life-threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L., has various biological functions, including anti-inflammatory, anti-cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)-induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP-infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF-κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c-Jun N-terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD-like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr-alleviated ALI via inhibiting pro-inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP-induced ALI.

Contribution of Chinese herbal medicine in the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of randomized controlled trials.

Coronavirus disease 2019 (COVID-19) has become a global epidemic, and there is no specific treatment for anti-COVID-19 drugs. However, treatment of COVID-19 using Chinese herbal medicine (CHM) has been widely practiced in China. PubMed, Embase, Cochrane Library, CNKI, Wanfang and VIP databases were searched to evaluate the efficacy and safety of CHM in the treatment of COVID-19. Twenty-six studies were included in this meta-analysis. The included cases were all patients diagnosed with COVID-19 according to the "New Coronary Virus Pneumonia Diagnosis and Treatment Program," with a total of 2,407 cases. Patients were treated with CHM, including 36 prescriptions, and 105 flavors of CHM were included. The results of the meta-analysis showed that the CHM group improved in lung CT, clinical cure rate, clinical symptom score and time to negative for viral nucleic acid. However, this study still has many limitations due to the limited number of included studies. Therefore, high-quality RCT studies are needed to provide more reliable evidence for CHM treatment of COVID-19. In conclusion, CHM may significantly improve the clinical manifestations and laboratory indicators of patients with COVID-19. In addition, no serious adverse reactions were found after CHM treatment. Therefore, CHM may be used as a potential candidate for COVID-19. HIGHLIGHTS: COVID-19 has become a global epidemic, and there is no specific treatment for anti-COVID-19 drugs. CHM has made a new breakthrough in the treatment of COVID-19. CHM may relieve lung CT images of COVID-19 patients. CHM may improve clinical symptoms of COVID-19 patients. CHM may inhibit the expression of inflammatory factors in patients with COVID-19.

The effects of Ophiocordyceps sinensis combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Ophiocordyceps sinensis (OS), a medicinal fungus, has been made into OS preparations, which are frequently used as adjunctive therapy for patients with Diabetic Kidney Disease (DKD) in China. It is necessary to assess the efficacy and safety of OS preparations in the adjunctive treatment of DKD by conducting a systematic review and meta-analysis. OBJECTIVE: Ophiocordyceps sinensis preparations were evaluated for their efficacy and safety as adjunctive therapy to conventional drugs (angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)) for DKD. METHODS: We searched seven electronic literature databases for randomized controlled trials (RCTs) comparing ACEI/ARB and OS combined with ACEI/ARB from inception up to March 2022. Two reviewers extracted data and assessed the risk of bias independently. Evidence certainty was rated using the GRADE system. Standardized mean difference (SMD) or mean difference (MD) was pooled with random effects models and was reported with corresponding 95% confidence intervals (CIs). Meta-analysis, sensitivity analysis and Egger's test were performed using R software (version 14.2) (PROSPERO registration no. CRD42021248634). RESULTS: Thirty eight RCTs involving 3167 patients met the inclusion criteria. No trials were reported with outcomes about kidney disease progression and cardiovascular events. In meta-analysis, compared with the control group of ACEI/ARB alone, OS combined with ACEI/ARB can achieve better effects in the treatment of DKD on reducing serum creatinine (Scr) [MDScr =-11.48 95% CI [-15.78, -7.18], p < 0.01], blood urea nitrogen (BUN) [MDBUN= -1.00, 95% CI [-1.44, -0.55], p < 0.01], ß2-microglobulin (ß2-MG) [SMDß2-MG= -1.32, 95% CI [-2.27, -0.37], p < 0.01], cystatin C (CysC) [MDCysC=-0.64, 95% CI [-0.83, -0.45], p < 0.01], 24-h urine proteinuria (24hUP) [SMD24hUP= -1.99, 95% CI [-2.68; -1.31], p < 0.01], urine microalbumin (UALB) [MDUALB= -37.41, 95% CI [-44.76, -30.06], p < 0.01] and decreasing urinary albumin excretion rate (UAER) [MDUAER= -24.11, 95% CI [-30.54, -17.68], p < 0.01] and albumin creatinine ratio (ACR) [SMDACR = 1.01, 95% CI [-1.73, -0.29], p < 0.01]. The OS adjuvant treatment also improved outcomes of blood pressure, blood glucose, blood lipid, inflammation and oxidative stress. No significant change in fasting blood glucose (FPG), glycated hemoglobin (HbA1c), malondialdehyde (MDA), and transforming growth factor beta 1 (TGF-ß1) was detected. Yet, no significant difference was found about the adverse events between the two groups. CONCLUSIONS: Ophiocordyceps sinensis preparation combined with ACEI/ARB has beneficial influence on renal function, decrease proteinuria, dyslipidemia, and even oxidative stress and inflammation in DKD patients. However, there is no trial that evaluated outcomes of kidney disease progression and cardiovascular events. Future study should move beyond surrogate endpoints to actual cardiovascular or renal outcome benefits with an aim to explore effects of OS preparation in the long-term.

Qizhi Kebitong Formula Ameliorates Streptozocin-Induced Diabetic Osteoporosis through Regulating the PI3K/Akt/NF-κB Pathway.

Background: Diabetic osteoporosis (DOP) is a progressive osteoblast dysfunction induced by high glucose, which has negative impacts on bone homeostasis. Qizhi Kebitong formula (QKF) is a traditional Chinese medicine (TCM) formula for treating DOP. However, its role in the protection of DOP has not been clarified yet. Here, we aimed to explore the potential mechanisms of QKF on DOP development via in vivo experiment. Methods: Network pharmacology was used to detect the key targets and signaling pathways of QKF on DOP. The effects of QKF on DOP were examined by the phenotypic characteristics, micro-CT, and hematoxylin-eosin (H&E) staining. The predicted targets and pathways were validated by a streptozocin- (STZ-) induced mouse model. Subsequently, the levels of the selected genes and proteins were analyzed using qRT-PCR and Western blot. Finally, AutoDock and PyMOL were used for molecular docking. Results: In this study, 90 active compounds and 2970 related disease targets have been found through network pharmacology. And QKF could improve the microstructures of femur bone mass, reduce inflammatory cell infiltration, and downregulate the levels of TNF-α, IKBKB, IL-6, and IL-1ß. Moreover, the underlying effect of PI3K/Akt/NF-κB pathways was also recommended in the treatment. Conclusion: Altogether, our findings suggested that QKF could markedly alleviate osteoblast dysfunction by modulating the key targets and PI3K/Akt/NF-κB signaling pathway.

Jiedu Tongluo Baoshen formula enhances podocyte autophagy and reduces proteinuria in diabetic kidney disease by inhibiting PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been applied to diabetic kidney disease (DKD). A large number of animal trials each year focus on TCM for DKD, but the evidence for these preclinical studies is not clear. AIM OF THE STUDY: The aim of this study was to study the therapeutic effect of Jiedu Tongluo Baoshen formula (JTBF) on DKD proteinuria and renal protection. At the same time, it is verified that JTBF can reduce podocyte injury by enhancing autophagy function, and then achieve the effect of proteinuria. MATERIALS AND METHODS: We use high performance liquid chromatography to detect and analyze the fingerprint of JTBF to find the chemical composition. Subsequently, we constructed a DKD rat model induced by high-fat diet and streptozocin (HFD + STZ). Urine and blood biochemical automatic analyzer were used to detect 24-h urine protein quantification (24 h-UP) and renal function. The renal pathological changes were observed by H&E and transmission electron microscopy (TEM), and the levels of autophagy-related proteins and mRNA in podocytes were detected by immunohistochemistry, RT-qPCR and Western Blot. The chemical composition of JTBF was screened from traditional Chinese medicine systems pharmacol (TCMSP) and PubChem databases, and the potential targets and associated pathways of JTBF were predicted using kyoto encyclopedia of genes and genomes (KEGG) and protein-protein interaction (PPI) network analysis in network pharmacology, and confirmed in animal experiments and histopathological methods. RESULTS: We discovered 77 active ingredients of JTBF. Through animal experiments, it was found that JTBF reduced 24 h-UP and promoted the expression of podocin, nephrin, and WT-1 in podocytes, thereby reducing podocyte damage. At the same time, JTBF activates the expression of podocyte autophagy-related proteins (beclin-1, LC3 and P62). Subsequently, through network pharmacology predictions, 208 compounds were obtained from JTBF, and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) was a potential signal pathway. JTBF was obtained in DKD rat kidney tissue to inhibit the expression of PI3K, Akt and mTOR related proteins. CONCLUSIONS: JTBF enhance podocyte autophagy to reduce podocyte damage, thereby effectively treating DKD proteinuria and protecting kidney function.

Anthocyanin Extract from Purple Sweet Potato Exacerbate Mitophagy to Ameliorate Pyroptosis in Klebsiella pneumoniae Infection.

Given the rise of morbidity and mortality caused by Klebsiella pneumoniae (KP), the increasing number of strains resistant to antibiotics, and the emergence of hypervirulent Klebsiella pneumonia, treatment of KP infection becomes difficult; thus, novel drugs are necessary for treatment. Anthocyanins, or natural flavonoids, have an extensive effect against bacterial infection. However, few studies on anti-KP are identified. Here, we evaluated the therapeutic effect of purple sweet potato anthocyanins (PSPAs) on KP, containing 98.7% delphinidin 3-sambubioside. Results showed that KP-infected mice after PSPAs treatment manifested decreased mortality, weakened lung injury, dampened inflammatory responses, and reduced bacterial systemic dissemination in vivo. In Vitro, PSPAs significantly suppressed pyroptosis and restricted NLRP3 inflammasome activation in alveolar macrophages infected with KP. As for the mechanism, PSPAs promote mitophagy by recruiting Parkin to the mitochondria. PSPAs-conferred mitophagy increased mitochondrial membrane potential and decreased mitochondrial reactive oxygen species and mitochondrial DNA, resulting in impaired NLRP3 inflammasome activation. In addition, the promotion of mitophagy by PSPAs required the Nrf2 signaling pathway. Collectively, these findings suggest that PSPAs are a potential option for the treatment of KP infection.

Cochlioquinone derivative CoB1 induces cytostatic autophagy in lung cancer through miRNA-125b and Foxp3.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide, yet no effective medication for this disease is available. Cochlioquinone B derivative (CoB1), purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana, affects the defense against pulmonary pathogens by regulating inflammatory responses. However, the effect of CoB1 on lung cancer and the underlying molecular mechanisms remain unknown. In the present study, we investigate the protective effects of CoB1 on lung cancer and explore its underlying mechanism. METHOD: We examined the inhibitory effect of CoB1 on lung cancer cells (A549 cells) by MTT and colony formation assay. The effect of CoB1 on cytostatic autophagy in lung cancer cells was verified by Western blot, transmission electron microscopy, and confocal microscopy. The differentially expressed miRNAs were identified using quantitative RT-PCR. Luciferase assay and Northern blot were performed to verify the correlation between miRNA-125b and Foxp3. Protein expression in autophagy-related pathways was detected by Western blot. Xenograft tumor models were constructed to explore the inhibitory effect of CoB1 and the role of miRNA-125b as a suppressor in lung cancer in vivo. RESULT: CoB1 inhibited lung cancer cell proliferation by inducing cytostatic autophagy both in vitro and in vivo. CoB1-induced autophagy was related to blocking of the PI3K/Akt1/mTOR signaling pathway. In addition, CoB1 induced miR-125b expression via activating the TAK1/MKK4/JNK/Smad axis, thereby reducing Foxp3 expression and further inducing autophagy. CONCLUSION: This study is the first to report the specific inhibitory function of CoB1 purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana in lung cancer, which may be due to the induction of autophagy. This study provides evidence and novel insights into the anticancer efficacy of CoB1.

Taxonomic importance of pollen morphology in Veratrum L. (Melanthiaceae) using microscopic techniques.

Previous studies reported that intrageneric relationships of genus Veratrum of family Melanthiaceae are controversial and hard to delimit. Therefore, we observed the pollen morphological features of six species in the genus Veratrum in detail using both light microscopy and scanning electron microscopy and investigated their significance for Veratrum taxonomy. Among them, five were studied for the first time. The results demonstrated that pollen grains of Veratrum are medium in size with P/E being 0.31-0.60. Three types of shape in polar view have been observed elliptic, long-elliptic, or wide-elliptic with blunt or rounded at both ends. Two types of width of colpus reported narrow or wide, two types of depth of colpus reported deep or flat, and two types of length of colpus reported extend almost or do not extend to the ends, whereas two types of colpus membranes reported absent or obvious. One type of surface ornamentation was noted as reticulate. These results support species Veratrum album and Veratrum lobelianum as well as Veratrum grandiflorum and Veratrum oxysepalum as two independent species, respectively, rather than classifying Veratrum into two sections. Overall, we demonstrated that the ratio of polar axis length to equatorial axial length, pollen characteristics at the polar view, the colpus morphology, and the surface ornamentation of pollen grains of genus Veratrum have important systematic significance in identification and delimitation of species.

Pollen morphology of Aletris L. (Nartheciaceae) and its systematic significance.

In this paper, we studied pollen morphologies of seven species in genus Aletris in detail by light microscopy and scanning electron microscopy. Of these, six species were reported for the first time. The palynological characteristics do not support the infrageneric classification into two clades. The results indicated that pollen grains of Aletris are small or medium with the P/E ratio of 0.36-0.59. They are elliptic or long-elliptic in the polar view with blunt, round or acute ends and bilateral symmetric with a monosulcate, narrow or wide, deep colpus that has length extending to the ends of pollen grains, obvious or absent colpus membranes. The pollen ornamentation is gemmate, perforated, or reticulate. The sexine is slightly or quite thicker than the nexine.

[Review on skin temperature of acupoints].

We retrieve and analyze the articles on body surface temperature of acupoints in the recent 50 years. Surface temperatures have been compared between acupoints and nonacupoints, and among acupoints in different states. The impacts of interventions for acupoint temperature are explored, including acupuncture,moxibustion and cupping, etc. We summarize the features and the rules of acupoint skin temperature. It is considered that there exists distribution rule for healthy people's acupoint skin temperature. That means acupoints have higher surface temperature than nonacupoints. In the same meridian the nearer acupoints close to the head and trunk, the higher the temperature is. The difference in symmetrical acupoints temperatures between the left and right side is about 0.5℃. In the different meridians the skin temperatures of adjacent acpoints are similar. The changes of acupoint's skin temperature in illness can be used as the auxiliary diagnosis. Acupuncture, moxibustion and cupping can produce acupoints stimulating, metabolism improving, yin-yang balance, acupoint temperature regulating. Thus,diseases are relieved. The specificity and regularity that acupoint's skin temperature presents may be one of the manifestations of the acupoint specificity, also it is an important starting point of the research on acupoint sensitization. The further studies should consider different diseases and modern biological engineering techniques, so that more rules of acupoints temperature can be found by more sensitive and objective temperature measurements as well as experimental and the mathematical models.

Bone uptake of Tc-99m MIBI in patients with hyperparathyroidism.

OBJECTIVE: The study aimed to investigate the incidence of bone uptake of tracer on Tc-99m MIBI imaging and explore its influencing factors and significance for diagnosis of metabolic bone disease (MBD) in patients with hyperparathyroidism (HPT). METHODS: Seventy-nine consecutive patients with histopathologically confirmed HPT (63 primary and 16 secondary) who had preoperative Tc-99m MIBI imaging were retrospectively evaluated. Serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) were measured for all patients, and serum alkaline phosphatase (ALP) was measured for 62 patients. Of the 79 patients, 50 underwent bone mineral density (BMD) examination and 30 underwent bone scintigraphy. The incidence and characteristics of abnormal bone uptake of MIBI were recorded. Mann-Whitney test was performed to determine if serum iPTH, Ca, P, ALP, and BMD were different between the patients with and without MIBI bone uptake. Logistic regression analysis was used to analyze the factors that influence the bone uptake of MIBI. The concordance rate between Tc-99m MIBI imaging and bone scintigraphy in delineating MBD was calculated. RESULTS: Tc-99m MIBI imaging disclosed the abnormal bone uptake of tracer in 22 (27.8 %) patients. Of them, 19 showed diffusely increased activity in skeleton, 2 showed focal uptake in brown tumors, and one showed both above patterns. Patients with bone uptake MIBI had higher level of serum iPTH (Z = -4.34, P < 0.001) and ALP (Z = -3.50, P < 0.001) than those without bone uptake. Logistic regression analysis also showed that bone uptake of MIBI was correlated with serum iPTH (OR = 4.42, P < 0.001) and ALP (OR = 3.21, P = 0.002). Among the 30 patients that underwent bone scintigraphy, 76.7 % patients showed signs of MBD, and the concordance rate between Tc-99m MIBI imaging and bone scintigraphy was 60 % for detecting MBD. CONCLUSIONS: Bone uptake of MIBI in patients with HPT is commonly related to a high level of iPTH and ALP; it probably reflects an active stage of MBD, and it should be monitored during the conventional Tc-99m MIBI scintigraphy.