Case analysis of brain abscesses caused by Nocardia asiatica: A case report / 中国热带医学

@#Abstract: Objective　To investigate the clinical characteristics and diagnosis key points of brain abscess caused by Nocardia asiatica, and provide a clinical basis for diagnosing and treating intracranial infection caused by Nocardia. Methods　A case of pulmonary Nocardia asiatica complicated with brain abscess diagnosed at the Second Affiliated Hospital of Hainan Medical University was selected to analyze the clinical manifestations, cerebrospinal fluid characteristics, pulmonary and cranial imaging features, and treatment plan, and to summarize the diagnosis and treatment experience. Results　The patient was an elderly woman with a history of diabetes, dry cough was the first symptom without fever or headache. At the beginning of the course, it was diagnosed as pulmonary infection and tuberculosis in the local hospital, and received conventional antimicrobial and anti-tuberculosis therapies, but showed no improvement. The patient developed progressive limb weakness, followed by consciousness disorders, and coma. Cerebrospinal fluid (CSF) adenosine deaminase and lactate dehydrogenase were not abnormal, CSF pressure, protein and white blood cells were high, mainly with multiple nuclear cells. CSF glucose and chloride were normal in the early stage of the disease, but decreased significantly in the later stage. Metagenomic analysis of cerebrospinal fluid indicated Nocardia asiatica with a specific sequence number of 537. Lung CT showed exudation, abscess, and cavity in the right lung. Skull MRI scan + enhancement suggested multiple scattered abscesses in both cerebral hemispheres. The abscesses were of different sizes and showed ring enhancement, with extensive surrounding edema, and ventricular compression. After treatment with meropenem, linezolid, and compound sulfamethoxazole tablets, the cerebrospinal fluid recovered, and the lesions in the lungs and intracranial structures improved. Conclusions　Brain abscess caused by Nocardia asiatica is similar to the tuberculous brain in clinical symptoms, cerebrospinal fluid examination, craniocerebral imaging, so we should be alert to the possibility of Nocardia infection in patients with diabetes. At the same time, metagenomic testing of the cerebrospinal fluid can help confirm the diagnosis. The mortality and disability rates of brain abscess caused by Nocardia are high. Early diagnosis and treatment can improve the prognosis.

Abietane-Type Diterpenoids From Nepeta bracteata Benth. and Their Anti-Inflammatory Activity.

Terpenes possess a wide range of structural features and pharmaceutical activities and are promising for drug candidates. With the aim to find bioactive terpene molecules, eight new compounds were isolated from the medicinal plant Nepeta bracteata Benth., including seven new abietane-type diterpenoids (1-7), along with a new ursane-type triterpenoid (8). The structures of compounds 1-8 were elucidated through the detailed spectroscopic analyses of their 1D and 2D NMR and MS data, and the absolute configurations of compounds 1-7 were determined by comparing their experimental and calculated ECD spectra. Compound 1 was a novel degraded carbon diterpene with the disappearing of methyl signal at C-19, while compound 7 possessed a new norabietane-type diterpenoid carbon skeleton with the presence of five-membered lactone arising from ring rearrangement. The anti-inflammatory of all obtained isolates were evaluated on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the results of anti-inflammatory activity screening showed that compared with the LPS model group, all compounds were significantly down-regulation the TNF-α inflammatory factor at the specific concentration, except for compound 6.

SIRT3-mediated mitochondrial unfolded protein response weakens breast cancer sensitivity to cisplatin.

BACKGROUND: Mitochondrial unfolded protein response plays an important role in the occurrence and development of breast cancer. However, the role of mitochondrial unfolded protein response (UPRmt) in the sensitivity of breast cancer to cisplatin chemotherapy has not yet been cleared. OBJECTIVES: The purpose of this study is to explore the role of mitochondrial unfolded protein response in breast cancer sensitivity to cisplatin. METHODS: In this study, qRT-PCR, Western blotting, Immunofluorescence, CCK-8, Colony formation, Transwell assay and TUNEL staining assay were used to confirm the role of UPRmt in breast cancer cells treated with cisplatin. RESULTS: Cisplatin increased the levels of UPRmt including CLPP, HSP60, LONP1 in MCF7 and MDA-MB-231 cells. UPRmt inducer Nicotinamide ribose (NR) could promote the proliferation and invasion of breast cancer cells treated with cisplatin. Importantly, SIRT3 was discovered to increase UPRmt in breast cancer cells and silencing of SIRT3 could inhibit the effect of NR in breast cancer. CONCLUSIONS: UPRmt regulated by SIRT3 could protect breast cancer cell from cisplatin. Controlling SIRT3-induced UPR may be a potential therapeutic target to increase the sensitivity of breast cancer chemotherapy.

Recent advances in natural anti-HIV triterpenoids and analogs.

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic is one of the world's most serious health challenges. Although combination antiretroviral therapy provides effective viral suppression, current medicines used against HIV cannot completely eradicate the infectious disease and often have associated toxicities and severe side effects in addition to causing drug resistance. Therefore, the continued development of new antiviral agents with diverse structures and novel mechanisms of action remains a vital need for the management of HIV/AIDS. Natural products are an important source of drug discovery, and certain triterpenes and their analogs have demonstrated potential as pharmaceutical precursors for the treatment of HIV. Over the past decade, natural triterpenoids and analogs have been extensively studied to find new anti-HIV drugs. This review discusses the anti-HIV triterpenoids and analogs reported during the period of 2009-2019. The article includes not only a comprehensive review of the recent anti-HIV agent development from the perspective of medicinal chemistry, but also discusses structure-activity relationship analyses of the described triterpenoids.

A new steroidal saponin from Polygonatum sibiricum.

A new furostan type steroidal saponin, kingianoside Z (1), along with four known compounds (2-5), was isolated from the ethanolic extract of Polygonatum sibiricum Delar. ex Redoute. Their structures were determined by spectroscopical method and by comparison with previously reported spectroscopic data. Compounds 3-5 showed significant cytotoxicity against HepG2 cell lines with IC50 values of 14.2, 12.1 and 8.5 µM, respectively.

Triterpenoid saponins from Clinopodium chinense (Benth.) O. Kuntze and their biological activity.

Four new ursane-type triterpenoid saponins, clinopoursaponins A-D (1-4), six new oleanane-type triterpenoid saponins, clinopodiside VII-XII (5-10), as well as eight known triterpene analogues (11-18), were isolated from the aerial parts of Clinopodium chinense (Benth.) O. Kuntze. The structures of the new compounds were determined based on extensive spectral analyses, including 1D (1H and 13C) and 2D NMR experiments (COSY, NOESY, HSQC, 2D TOCSY, HSQC-TOCSY and HMBC), HR-ESI-MS and chemical methods. Compounds 1-18 were evaluated for their protective effects against anoxia/reoxygenation-induced apoptosis in H9c2 cells and cytotoxicities against murine mammary carcinoma cell line 4T1. Compounds 8, 9 and 18 exhibited significant protective effects, while compound 1 exhibited cytotoxic activity with IC50 value of 7.4 µm compared to 7.6 µm for the positive control 10-hydroxycamptothecin.

New Cassane Diterpenoids from Caesalpinia sappan and their Antiplasmodial Activity.

One new cassane diterpene possessing an unusual N bridge between C-19 and C-20 named caesalsappanin R (1), as well as another new diterpene caesalsappanin S (2), were isolated from the seeds of Caesalpinia sappanwith methanol extract. Their structures were determined by spectroscopic analysis and examined alongside existing data from prior studies. Their biological activities were profiled by their antiplasmodial activity.

[Studies on chemical constituents of Clinopodium chinense].

Twenty-eight compounds were isolated and purified from Clinopodium chinense by Sephedax LH-20, ODS, MCI and preparative HPLC. Their structures were identified as apigenin (1), apigenin-7-O-ß-D-glucopyranoside (2), apigenin-7-O-ß-D-glucuronopyranoside (3), thellungianol (4), apigenin-7-O-ß-D-rutinoside (5), luteolin (6), luteolin-4'-O-ß-D-glucopyranoside (7), apigenin-7-O-ß-D-pyranglycuronate butyl ester (8), luteolin-7-O-ß-D-rutinoside (9), luteolin-7-O-ß-D-noehesperidoside (10), acacetin (11), acacetin-7-O-ß-D-glucuronopyranoside (12), buddleoside (13), naringenin (14), pruning (15), nairutin (16), isosakuranetin (17), isosakuranin (18), didymin (19), hesperidin (20), kaempferol (21), quercetin (22), kaempferol-3-O-α-L-rahmnoside (23), p-hydroxycinnamic acid (24), caffeic acid (25), cis-3-[2-[1-(3,4-dihydroxy-phenyl)-1 -hydroxymethyl]-1,3-ben-zodioxol-5-yl]-(E)-2-propenoic acid (26), mesaconic acid (27), gentisic acid 5-O-ß-D-(6'-salicylyl)-glucopyranoside (28). Among them, compounds 7, 9-10, 12, 23, 26-28 were isolated from the Clinopodium for the first time. The protective effects of compounds 1-6, 8-17 and 19 against H2O2-induced H9c2 cardiomyocyte injury were tested, compounds 15 exhibited significantly protective effects. Compared with the cell viability of (62.12±6.18)% in the model, pruning exhibited viabilities of (84.25±7.36)% at 25.0 mg•L⁻¹, respectively, using quercetin as a positive control [cell viability of (84.55±8.26)%, 20 mg•L⁻¹].

Soulieoside O, a new cyclolanostane triterpenoid glycoside from Souliea vaginata.

A new cyclolanostane triterpenoid glycoside, soulieoside O (1), together with 25-O-acetylcimigenol-3-O-ß-d-xylopyranoside (2) and cimigenol-3-O-ß-d-xylopyranoside (3), was isolated from the rhizomes of Souliea vaginata. Their structures were characterized by spectroscopic analysis and chemical methods. The new compound showed moderate inhibitory activity against three human cancer cell lines with IC50 values of 9.3-22.5 µM.

A new cycloartane triterpenoid glycoside from Souliea vaginata.

One new cycloartane triterpenoid glycoside, soulieoside Q (1), together with four known compounds (2-5) were isolated from the ethanolic extract of the rhizomes of Souliea vaginata Maxim. The structure of the new compound was determined by extensive spectroscopic analysis including 1D and 2D NMR and HRESIMS, as well as chemical methods. Compound 1 was evaluated for its cytotoxic activities against HepG2 and A549 cancer cell lines.

Effect of Smo SiRNA-mediated Hedgehog Signaling Pathway Inhibition on Palatal Fusion.

We used Smo siRNA to inhibit hedgehog signaling pathway in embryonic day (E) 13 palatal shelves in organ culture. SiRNA 4 was chosen as the most efficient from four synthesized Smo siRNAs. Palatal shelf fusion rate of 4 µg/mL cyclopamine group was the lowest and significantly lower than that of blank control group (P<0.05), and that of siRNA 4 group was also lower than that of blank control group (P=0.183). At 48 h after transfection, Smo protein level of siRNA 4 group was 64.8% lower than that of blank control group (P<0.05), and Gli1 protein level of 4 µg/mL cyclopamine group was 68.9% lower than that of blank control group (P<0.05). Hedgehog signaling pathway inhibition decreased palatal fusion in organ culture, probably owing to downregulation of Smo and Gli1 proteins.

A new cycloartane triterpene glycoside from Souliea vaginata.

A new cycloartane-type triterpene glycoside, namely soulieoside M (1), and one known compound, beesioside I (2), were isolated from the ethanolic extract of the rhizomes of Souliea vaginata. Their structures were determined spectroscopically and compared with previously reported spectral data. Compounds 1 and 2 were evaluated for their cytotoxic activities against three human cancer cell lines.

SRPK2 promotes the growth and migration of the colon cancer cells.

Colon cancer is one of the major causes of cancer-related death in the world. Understanding the molecular mechanism underlying this malignancy will facilitate the diagnosis and treatment. Serine-arginine protein kinase 2 (SRPK2) has been reported to be upregulated in several cancer types. However, its expression and functions in colon cancer remains unknown. In this study, it was found that the expression of SRPK2 was up-regulated in the clinical colon cancer samples. Overexpression of SRPK2 promoted the growth and migration of colon cancer cells, while knocking down the expression of SRPK2 inhibited the growth, migration and tumorigenecity of colon cancer cells. Molecular mechanism studies revealed that SRPK2 activated ERK signaling in colon cancer cells. Taken together, our study demonstrated the tumor promoting roles of SRPK2 in colon cancer cells and SRPK2 might be a promising therapeutic target for colon cancer.

A new phenylethanoid glycoside from Incarvillea compacta.

A new phenylethanoid glycoside, 3'''-O-methylcampneoside I (1), was isolated from the 90% ethanolic extract of the roots of Incarvillea compacta, together with three known compounds, campneoside I (2), ilicifolioside A (3), and campneoside II (4). Their structures were determined spectroscopically and compared with previously reported spectral data. Compound 1 existed as epimers and displayed better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-free radical scavenging activity using di-tert-butyl-4-methylphenol (BHT) as the positive control. In addition, pretreatment of human HepG2 cells with compound 1 significantly increased the viability on CCl4-induced cell death.

Two new abietane diterpenoid glycosides from Clinopodium chinense.

Two new abietane diterpenoid glycosides, named clinopoditerpenes B (1) and C (2), were isolated from Clinopodium chinese. The structures of the new compounds were determined on the basis of extensive spectral analysis. Compound 1 exhibited cardioprotective effect against H2O2-induced apoptosis in H9c2 cells.

A new sesquiterpenoid quinone with cytotoxicity from Abelmoschus sagittifolius.

A new sesquiterpenoid quinone, Acyl hibiscone B (1), together with five known compounds, (R)-lasiodiplodin (2), (R)-de-O-methyllasiodiplodin, (3) dibutyl phthalate (4), (R)-9-phenylnonan-2-ol (5) and hibiscone B (6), was obtained from the stem tuber of Abelmoschus sagittifolius. The structure of compound 1 was elucidated by analysing its (1)H and (13)C NMR, (1)H-(1)H COSY, HSQC, HMBC, NOESY and HR-ESI-MS values. Compound 1 showed significant cytotoxicity against Hela and HepG-2 human cancer cell lines.

A new labdane diterpene from the rhizomes of Alpinia officinarum.

A new labdane diterpene, (Z)-12,14-labdadien-15(16)-olide-17-oic acid (1), and a new natural cadinane sesquiterpene, 4-isopropyl-6-methyl-1-naphthalenemethanol (2), were isolated from the ethanolic extract of the rhizomes of Alpinia officinarum, together with three other products, galangin (3), kaempferol (4) and quercetin (5). Their structures were elucidated by using extensive spectroscopic methods. Compounds 1 and 2 showed no remarkable cytotoxic activity against HeLa and HepG2 cancer cell lines with IC50>50 µg mL(- 1).

Four new phenolic acid with unusual bicycle [2.2.2] octane moiety from Clerodendranthus spicatus and their anti-inflammatory activity.

Four new phenolic acids, clerodens A-D (1-4) possessing an unusual bicycle [2.2.2] octane moiety were isolated from the whole plants of Clerodendranthus spicatus. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and ECD data. All isolates were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7, and compound 4 showed significant inhibitory activities with IC50 value of 6.8 µM.

Effect of radiation on cytotoxicity, apoptosis and cell cycle arrest of human osteosarcoma MG-63 induced by a ruthenium(II) complex.

Radiation has large influence on the cytotoxicity, apoptosis and cell cycle arrest. The bioactivity of ruthenium(II) complex [Ru(dmb)2(DBHIP)](ClO4)2 (Ru1) (DBHIP=2-(3,5-dibromo-4-hydroxylphenyl)imidazo[4,5-f][1,10]phenanthroline) was investigated in the absence and presence of radiation. The cytotoxicity of Ru1 against MG-63 cells was evaluated by CCK-8 method. Ru1 shows high cytotoxicity upon radiation. Radiation can enhance the cytotoxicity of Ru1 on MG-63 cells. The apoptosis was studied by Hoechst 33258 staining method and flow cytometry. The reactive oxygen species, mitochondrial membrane potential, cell cycle arrest and western blot analysis were investigated in detail. The complex induces the apoptosis in MG-63 cells through ROS-mediated mitochondrial dysfunction pathway.