Antibacterial micro/nanomotors: current research progress, challenges, and opportunities.

Bacterial infections remain a formidable threat to human health, a situation exacerbated by the escalating problem of antibiotic resistance. While alternative antibacterial strategies such as oxidants, heat treatments, and metal nanoparticles (NPs) have shown potential, they come with significant drawbacks, ranging from non-specificity to potential environmental concerns. In the face of these challenges, the rapid evolution of micro/nanomotors (MNMs) stands out as a revolutionary development in the antimicrobial arena. MNMs harness various forms of energy and convert it into a substantial driving force, offering bright prospects for combating microbial threats. MNMs' mobility allows for swift and targeted interaction with bacteria, which not only improves the carrying potential of therapeutic agents but also narrows the required activation range for non-drug antimicrobial interventions like photothermal and photodynamic therapies, substantially improving their bacterial clearance rates. In this review, we summarized the diverse propulsion mechanisms of MNMs employed in antimicrobial applications and articulated their multiple functions, which include direct bactericidal action, capture and removal of microorganisms, detoxification processes, and the innovative detection of bacteria and associated toxins. Despite MNMs' potential to revolutionize antibacterial research, the translation from laboratory to clinical use remains challenging. Based on the current research status, we summarized the potential challenges and possible solutions and also prospected several key directions for future studies of MNMs for antimicrobial purposes. Collectively, by highlighting the important knowns and unknowns of antimicrobial MNMs, our present review would help to light the way forward for the field of antimicrobial MNMs and prevent unnecessary blindness and detours.

Traditional Chinese medicine manipulative reduction combined with percutaneous vertebroplasty for treating type III Kummell's disease: A case report.

BACKGROUND: A patient with type III Kummell's disease had a ruptured posterior cortex of the fractured vertebral body, which caused spinal cord compression. An open surgery was considered the best choice of operation. However, the patient and her family refused open surgery and instead demanded a minimally invasive surgical treatment such as percutaneous vertebroplasty (PVP). After preoperative discussion, we finally adopted the novel therapy of traditional Chinese medicine manipulative reduction (TCMMR) combined with PVP. CASE SUMMARY: A patient with type III Kummell's disease exhibiting bone block-induced spinal cord compression was admitted to our hospital. She suffered from a variety of medical disorders but refused open surgery, and instead asked for PVP surgery. TCMMR, in parallel with PVP, was used to restore the height of the compressed vertebral body and reduce the symptoms of spinal cord compression by the bone block in order to strengthen the vertebral body and prevent further collapse. The surgery was very successful. The height of the compressed vertebra was restored, and the symptom of spinal cord compression by bone block was reduced successfully via TCMMR. The fractured vertebra was solidified by the PVP. The pain visual analog score declined from preoperative 7 scores to postoperative 2 scores, and the Frankel spinal cord scale increased from preoperative D degree to postoperative E degree. CONCLUSION: The new method has advantages in treating patients with type III Kummell's disease who cannot be treated with open surgery.

Transcriptome-based identification and expression characterization of RgABCC transporters in Rehmannia glutinosa.

ABCC multidrug resistance-associated proteins (ABCCs/MRPs), a subfamily of ABC transporters, are involved in multiple physiological processes. Although these proteins have been characterized in some plants, limited efforts have been made to address their possible roles in Rehmannia glutinosa, a medicinal plant. Here, we scanned R. glutinosa transcriptome sequences and identified 18 RgABCC genes by in silico analysis. Sequence alignment revealed that the RgABCCs were closely phylogenetically related and highly conserved with other plant ABCCs/MRPs. Subcellular localization revealed that most of the RgABCCs were deposited in vacuoles and a few in plasma membranes. Tissue-specific expression of the RgABCCs indicated significant specific accumulation patterns, implicating their roles in the respective tissues. Differential temporal expression patterns of the RgABCCs exhibited their potential roles during root development. Various abiotic stress and hormone treatment experiments indicated that some RgABCCs could be transcriptionally regulated in roots. Furthermore, the transcription of several RgABCCs in roots was strongly activated by cadmium (Cd), suggesting possible roles under heavy metal stresses. Functional analysis of RgABCC1 heterologous expression revealed that it may increase the tolerance to Cd in yeast, implying its Cd transport activity. Our study provides a detailed inventory and molecular characterization of the RgABCCs and valuable information for exploring their functions in R. glutinosa.

Integrated miRNA-mRNA analysis reveals the roles of miRNAs in the replanting benefit of Achyranthes bidentata roots.

The yield and quality of the medicinal plant Achyranthes bidentata can be increased when it is replanted into a field cultivated previously with the same crop, however, fundamental aspects of its biology (so-called "replanting benefit") still remain to be elucidated. miRNAs are sRNA molecules involved in the post-transcriptional regulation of gene expression in plant biological processes. Here, 267 conserved and 36 novel miRNAs were identified in A. bidentata roots. We compared the miRNA content of the roots (R1) from first-year planting with that of the roots (R2) of second-year replanting, and screened 21 differentially expressed (DE) miRNAs. Based on in silico functional analysis, integrated miRNA-mRNA datasets allowed the identification of 10 miRNA-target family modules, which might participate in the benefit. The expression profiles of the miRNA-target modules were potentially correlated with the presence of the replanting benefit. The indication was that the miRNA-responsive continuous monoculture could reprogram miRNA-mRNA expression patterns, which possibly promote the root growth and development, enhance its transport activity and strengthen its tolerance to various stresses, thereby improving A. bidentata productivity as observed in the replanting benefit. Our study provides basic data for further research on the molecular mechanisms of the benefit in A. bidentata.

[Effects of saikosaponin b_2 on inflammation and energy metabolism in mice with acute liver injury induced by LPS/GalN].

To study the effects of saikosaponin b2( SS-b2) on inflammatory factors and energy metabolism against lipopolysaccharide/galactosamine( LPS/Gal N) induced acute liver injury in mice. Mice were randomly divided into normal group( equal amount of normal saline),model group( 100 g·kg~(-1) LPS and 400 mg·kg~(-1) Gal N),low,medium,high dose group of SS-b2( SS-b25,10,20 mg·kg~(-1)·d-1) and positive control group( dexamethasone,10 mg·kg~(-1)). All of the groups except for the normal group were treated with LPS/Gal N though intraperitoneally injection to establish the acute liver injury model. The organ indexes were calculated. The levels of serum transaminases( ALT and AST) and the activities of ATPase( Na+-K+-ATPase,Ca2+-Mg2+-ATPase) in liver were detected. The activity of tumor necrosis factor-α( TNF-α),interleukin-1ß( IL-1ß) and interleukin-6( IL-6) were determined by the enzyme-linked immunosorbent assay( ELISA). The contents of lactate dehydrogenase( LDH) in liver were determined by micro-enzyme method. HE staining was used to observe the histopathological changes of the liver. Histochemical method was used to investigate the protein expression of liver lactate dehydrogenase-A( LDH-A). The protein expressions of Sirt-6 and NF-κB in the liver were detected by Western blot. According to the results,compared with the model group,there were significant changes in organ indexes in the high-dose group of SS-b2( P<0. 05). The level of ALT,AST,TNF-α,IL-1ß,IL-6 and the activities of LDH in serum of mice with liver injury were significantly reduced in the medium and high dose groups of SS-b2( P<0. 01). With the increase of the concentration of SS-b2,the range of hepatic lesions and the damage in mice decreased. The activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in liver of mice were significantly enhanced in each dose group( P<0. 01). The expression of NF-κB in liver tissues was significantly down-regulated in the medium and high dose group( P<0. 01). Meanwhile,the expression of Sirt-6 protein in the liver of mice with acute liver injury was significantly increased in each dose group( P<0. 01).In summary,SS-b2 has a significant protective effect on LPS/Gal N-induced acute liver injury in mice,which may be related to the down-regulation of NF-κB protein expression and up-regulation of Sirt-6 protein expression to improve inflammatory injury and energy metabolism.

The root transcriptome of Achyranthes bidentata and the identification of the genes involved in the replanting benefit.

KEY MESSAGE: The transcriptome profiling in replanting roots revealed that expression pattern changes of key genes promoted important metabolism pathways, antioxidant and pathogen defense systems, adjusted phytohormone signaling and inhibited lignin biosynthesis. The yield of the medicinal plant Achyranthes bidentata could be significantly increased when replanted into a field cultivated previously for the same crop, but the biological basis of this so-called "replanting benefit" is unknown. Here, the RNA-seq technique was used to identify candidate genes responsible for the benefit. The analysis of RNA-seq libraries prepared from mRNA extracted from the roots of first year planting (normal growth, NG) and second year replanting (consecutive monoculture, CM) yielded about 40.22 GB sequencing data. After de novo assembly, 87,256 unigenes were generated with an average length of 1060 bp. Among these unigenes, 55,604 were annotated with public databases, and 52,346 encoding sequences and 2881 transcription factors were identified. A contrast between the NG and CM libraries resulted in a set of 3899 differentially transcribed genes (DTGs). The DTGs related to the replanting benefit and their expression profiles were further analyzed by bioinformatics and qRT-PCR approaches. The major differences between the NG and CM transcriptomes included genes encoding products involved in glycolysis/gluconeogenesis, glutathione metabolism and antioxidant defense, in aspects of the plant/pathogen interaction, phytohormone signaling and phenylpropanoid biosynthesis. The indication was that replanting material enjoyed a stronger level of defense systems, a balance regulation of hormone signals and a suppression of lignin formation, thereby promoting root growth and development. The study provides considerable significant insights for a better understanding of the molecular mechanism of the replanting benefit and suggests their possible application in developing methods to reinforce the effects in medicinal plants.

Effects of Evodiamine on the Pharmacokinetics of Dapoxetine and Its Metabolite Desmethyl Dapoxetine in Rats.

The objective of this work was to investigate the effect of orally administered evodiamine on the pharmacokinetics of dapoxetine and its active metabolite desmethyl dapoxetine in rats. Twelve healthy male Sprague-Dawley rats were randomly divided into 2 groups: the control group (received oral 10 mg/kg dapoxetine alone) and the combination group (10 mg/kg dapoxetine orally co-administered with 100 mg/kg evodiamine). The plasma concentration of dapoxetine and desmethyl dapoxetine were estimated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and different pharmacokinetic parameters were calculated using the Drug and Statistics 2.0 software. Compared to the control group, the pharmacokinetic parameter of t1/2, AUC(0-∞) and Tmax of dapoxetine in combination group was significantly increased by 63.3% (p < 0.01), 44.8% (p < 0.01) and 50.4% (p < 0.01), respectively. Moreover, evodiamine had significantly decreased the pharmacokinetic parameter of t1/2 and AUC(0-∞) of desmethyl dapoxetine. This study demonstrated that evodiamine inhibits the metabolism of dapoxetine. Henceforth, the pharmacodynamic influence of this interaction should be taken into consideration while prescribing dapoxetine to the patients already taking evodiamine.

[Effect of radix sophorae flavescentis (RSF) mixture on mast cells in jejunal mucosa of mice infected by Cryptosporidium].

OBJECTIVE: To elucidate the role of mast cells (MC) activation in the jejunal mucous membrane in the pathogenesis of cryptosporidiosis (CPS) and explore the mechanism of prevention and treatment of radix sophorae flavescetis(RSF) mixture on CPS. METHODS: A total of 30 healthy male BALB/c mice were randomly divided into a normal control group, CPS model control group and RSF mixture experimental group. The mice of CPS model were inoculated intragastrically with 1 x 10(5) Cryptosporidium oocyst (CSO). The mice in the RSF mixture experimental group were treated with inoculation of RSF mixture (0.2 ml doses) twice one week for three weeks continuously after CPS models were established. Pathological changes of the jejunal mucosa membrane were observed by a light microscope. The MCs were stained by toluidine blue, the number of mast cells was recorded and the changes of degranulation were observed. RESULTS: The HE staining showed inflammatory pathological changes in the jejunal mucosa membrane of the CPS model control group. After three-week treatment of RSF mixture, the small intestine epithelium was integrated on the whole. The toluidine blue stain showed the number of mast cell in submucosa and muscular layer of the jejunal mucous membrane increased significantly in the model control group (12.80 +/- 0.84) compared with those of the normal control group (1.60 +/- 0.89) (P < 0.01) and an obvious degranulation was seen in the CPS model control group. The number of mast cells of the mice in the RSF mixture experimental group decreased significantly (P < 0.01) and the number (2.00 +/- 0.71) and morphous were closed to the normal after administration for three weeks. CONCLUSIONS: MC activation is involved in the intestinal inflammatory response caused by Cryptosporidium. RSF mixture could decline the number of MC, inhibit the activation and degranulation of MC in the jejunal mucosa membrane of CPS mice to reduce inflammation and repair the damaged intestinal mucosa, which may realize the purpose of treatment of CPS.

[Protective effect of radix sophorae flavescentis mixture on intestinal mucosa in mice infected with Cryptosporidium parvum].

OBJECTIVE: To investigate the protective effect of radix sophorae flavescentis (RSF) mixture on intestinal mucosa in mice infected with Cryptosporidium parvum. METHODS: Thirty BALB/c male mice were randomly divided into control group, infection group and RSF mixture treatment group. Mice of the posterior two groups were inoculated intragastrically with 1 x 10(5) C. parvum oocysts, immunosuppressed with dexamethasone (5 microg/ml) and gentamycin sulfate (40 microg/ml) in drinking water. At the 8th day post-infection, mice in RSF mixture treatment group were treated with 0.2 ml dose of RSF mixture twice a week (three-day intervals) for three weeks. The mice in infection group and RSF mixture treatment group were monitored for oocyst shedding in fecal pellets every two days after treatment. At 28 days after infection, experimental mice were sacrificed, jejunal tissue was removed for preparation of paraffin-embedded sections. The changes of CD3+, CD4+, CD8+ T lymphocytes and IgA plasmocytes in intestinal mucosa were determined by immunohistochemistry. In addition, jejunum of infected mice and treated mice were collected, and ultrastructural changes were observed under electron microscopy. RESULTS: Compared with infection group, the level of oocyst shedding was obviously lower and the time of the oocyst discharging was significantly shorter in RSF mixture treatment group. The proportion of CD3+, CD4+ T lymphocyte and CD4+/CD8+ T cell ratio in infection group (49.7% +/- 2.4%, 25.7% +/- 2.2%, 1.1 +/- 0.3) were significantly lower than that of treatment group (62.4% +/- 1.4%, 37.5% +/- 3.1%, 1.5 +/- 0.3) and control group (66.5% +/- 1.9%, 40.1% +/- 1.8%, 1.5 +/- 0.2) (P < 0.01). CD8+ T lymphocytes showed no significant difference in each group (P > 0.05). The number of IgA plasmocytes in treatment group (52.7 +/- 3.5) was significantly higher than that of control group (8.3 +/- 2.3) and infection group (33.7 +/- 2.6) (P < 0.01). After administration for three weeks, the damaged C. parvum parasites were seldom seen in mouse jejunum, and lysosomes appeared in large number, RSF mixture treatment improved mitochondrial structure and repaired microvilli. In infection group, mitochondria ridges were significantly broken and microvilli surrounding C. parvum oocysts were shed, resulting in the appearance of crater-like lesions on the surface, the oocyst wall and host cell membrane fused together. CONCLUSION: RSF mixture is effective against Cryptosporidium parvum. The damage of intestinal mucosa in infected mice can be repaired after treatment.

[Apoptotic mechanism of gecko crude peptides on human liver carcinoma cell line HepG2].

OBJECTIVE: To investigate the effect of Gecko crude peptides (GCPS) on human liver carcinoma HepG2 cells and its mechanism. METHODS: MTT assay was used to analyze the effect of the GCPS on the proliferation of HepG2 Cell; Nucleus change of HepG2 treated with GCP was observed by Hoechst33258 fluorescence staining, and BAX and BCL-2 were detected with western-blot assay. RESULTS: GCPS could inhibit the proliferation of HepG2 Cell in a time and dosage dependent way, and its half-maximal inhibitory concentration (IC50) was 1.2 mg/mL; HepG2 pretreated with GCPS showed apoptotic morphological changes. GCPS (1.6 mg/mL, 0.8 mg/mL) could decrease the expression of BCL-2 protein, and increase the expression of BAX protein. CONCLUSION: GCPS can inhibit the proliferation of HepG2 cell. The mechanism may be related to the induction apoptosis of HepG2.

[Effect of Cornus officinalis fruit core extract on the cardiac hypertrophy induced by two kidney two clip].

OBJECTIVE: To observe the effect of Cornus officinalis fruit core extract on cardiac hypertrophy induced by two kidney two clip (2K2C) and its mechanism. METHODS: Male Sprague-Dawley rats were randomly divided into 4 groups: sham-operated group, model group and treatment groups (300, 600 mg/kg). Rats were intragastric administered medicine for 4 weeks from the fourth week after surgery. Sham-operated and 2K2C rats were given vehicle for 4 weeks. Blood pressure and hemodynamic parameters were measured. Left ventricular weight to body weight (LVM/BM) ratio was calculated. Paraffin-embedded hearts were cut into 5 microm slices, which were stained with hematoxylin-eosin (HE) and Masson for morphological analysis; Western-blot analysis was performed to investigate the effects of Cornus officinalis fruit core extract on the expression of P47phox, Nox4 in myocardium. RESULTS: Compared with sham-operated group, the blood pressure and LVM/BM ratios were markedly elevated in model groups. Meanwhile cardiomyocyte cross sectional areas was markedly increased and myocardial fibers showed disordered arrangement while these parameters were markedly reversed after treatment with Cornus officinalis fruit core extract for 4 weeks. At 8th weeks after operation, model rats developed obvious LV hypertrophy. Cornus officinalis fruit core extract, more significant in high dose, decreased the blood pressure and LVM/BM ratios and reversed the cardiomyocyte hypertrophy and myocardial fibrosis. Moreover, Cornus officinalis fruit core extract decreased the expression of P47phox and Nox4 which elevated in LV in model rats. CONCLUSION: Cornus officinalis fruit core extract could significantly decrease the blood pressure, reverse cardiac hypertrophy and improve the function of heart which is possibly associated with the down-regulation of P47phox and Nox4.

[Inhibitory effects of Gecko alcohol extract on human esophageal squamous carcinoma cell line EC-109 proliferation and associated mechanism].

OBJECTIVE: To explore the proliferation inhibition effects of Gecko alcohol extract (GAE) on human esophageal squamous carcinoma cell line EC-109 and its mechanism. METHODS: The inhibitory effects of GAE on proliferation of EC-109 cells were measured by MTT. Nucleolus change of apoptotic cells was observed by Hoechest33342 fluorescence staining. Apoptosis rate of EC-109 cells was detected by flow cytometry. The expressions of apoptosis protein Caspase-3 and FAS in EC-109 cells were investigated by immunohistochemistry. RESULTS: GAE had the inhibition effects on the proliferation of esophageal carcinoma cell EC-109. The apoptosis rate of EC-109 cell treated with GAE(3.0 mg/mL, 4.0 mg/mL) for 48h was 20.63% and 39.73%, respectively. Compared with control group,the expression of Fas and Caspase-3 was significantly up-regulated in GAE treated group. CONCLUSION: GAE can inhibit the proliferation of esophageal carcinoma EC-109 cells and induce them apoptosis which may be correlated with increasing expression of protein Fas and Caspase-3.

[Study on the antitumor effects and synergism and attenuation effects of gecko alcohol extract].

OBJECTIVE: To investigate the antitumor effects of Gecko alcohol extract and its synergism and attenuation effects on CTX. METHOD: S180-bearing mice were given Gecko alcohol extract via intravenous injection,the tumor inhibitory rate and the levels of serum TNF-alpha of mice were detected. After inoculation of S180 tumor, the synergism and attenuation effects of Gecko alcohol extract on CTX were observed. After 12 days treatment, the tumor inhibitory rate, the count of peripheral white blood cells, index of thymus and spleen were calculated. RESULTS: Gecko alcohol extract in different dose (0.6, 1.2, 2.4 g/kg) inhibited the growth of S180 sarcoma in KM mice. The tumor inhibitory rates of 0.6, 1.2, 2.4 g/kg Gecko alcohol extract were 44.88%, 63.94%, 69.53%, respectively. However, the levels of serum TNF-alpha of mice not changed. The tumor inhibitory rates of intravenous administration of 0.6, 1.2, 2.4 g/ kg Gecko alcohol extract combined with CTX (20 mg/kg) were 56.93%, 67.15%, 70.24%, which were higher than that of CTX administration alone (41.71%). Compared with those in CTX group, the count of WBC (P < 0.01), the indexes of thymus and spleen (P < 0.05) were significantly elevated in all Gecko alcohol extract and CTX combination groups. CONCLUSION: Gecko alcohol extract has anti-tumor effects in vivo and attenuation effects on CTX.

[Regulation of telomerase activity and cell cycle of K562 cells by oridonin].

AIM: To investigate the effect of oridonin (ORI) on telomerase activity and cell cycle of human leukemic cell line K562 cells. METHODS: Immunohistochemistry (IHC) technique was used to determine the expression of hTERT or C-myc. Telomerase activity was detected with TRAP-PCR-ELISA assay. In addition, the percentages of K562 cells in different cell cycle were determined by flow cytometry (FCM) at 24th and 48th hours separately after adding the different concentrations of ORI. RESULTS: After the K562 cells were treated with ORI at 3.43 micromol x L(-1) for 48 h, the expression of hTERT and C-myc decreased obviously. There was statistical significant (P < 0.05) difference between experimental groups and the normal controls. In addition, the telomerase activity of K562 cells was significantly inhibited by ORI at the dose of 3.43 micromol x L(-1) for 48 h. At the same time, the cell cycle distribution changed, the percentage of G0/G1 or G2/M stages cells increased and that of the S stage cells decreased after ORI was added. CONCLUSION: ORI can effectively inhibit telomerase activity in K562 cells. Arresting cell cycle and decreasing the expression of hTERT and C-myc may be the mechanism of action.