Clinical Effects of Biling Weitong Granules in Combination with Quadruple Therapy on Refractory Helicobacter pylori Infection.

Objective: The prevalence of antimicrobial resistance in Helicobacter pylori (HP) infection has increased globally. This study aimed to compare the efficacy of Biling Weitong granules (BLWTG) combined with quadruple therapy in patients with refractory HP infection who had previously failed eradication therapy. Methods: This single-center prospective study enrolled patients with two or more consecutive failed HP treatments. A total of 122 patients with previously failed HP treatment from our hospital were recruited as participants and randomly (1:1) allocated to two eradication groups: patients treated with bismuth-containing quadruple therapy (esomeprazole 40 mg, amoxicillin 1.0 g, bismuth potassium citrate 220 mg, and clarithromycin 500 mg, twice daily [EACB group]) for 14 days. And those treated with BLWTG (5 g three times daily) combined with the EACB group for 14 days (BLWTG+EACB group). The therapeutic effects of the two treatment programs were comprehensively evaluated. Results: The study group had a significantly higher improvement rate in symptoms (dull stomach pain, nausea, gastric distension, loss of appetite, and belching) compared to the control group (P < .05). Eight weeks after drug withdrawal, the eradication rates in the control and study groups were 49.18% and 73.77%, respectively. The levels of interleukin-6, C-reactive protein, and tumor necrosis factor-α were significantly lower in both groups after treatment but were significantly lower in the study group than in the control group (P < .05). Conclusions: The combination of BLWTG and standard four-drug therapy had a high eradication rate and low recurrence rate in patients with refractory HP infection. Additionally, this combined therapy could regulate inflammatory reactions and reduce drug-related adverse reactions.

High-dose amoxicillin-proton pump inhibitor dual therapy as first-line treatment for Helicobacter pylori infection in Northwest China: A prospective, randomised controlled trial.

AIMS: We aimed to assess the eradication efficacy and factors that influencing it of high-dose dual therapy (HDDT) in Gansu region, Northwest China. METHODS: A total of 216 treatment-naive patients with Helicobacter pylori infection were randomly assigned to two groups for the 14-day eradication treatment: the HDDT group (amoxicillin 750 mg q.i.d. and esomeprazole 40 mg t.i.d.) and the amoxicillin and clarithromycin-containing bismuth quadruple therapy group (ACBQT: esomeprazole 20 mg, bismuth potassium citrate 2 g, amoxicillin 1 g, and clarithromycin 500 mg; b.i.d.). The eradication rates, adverse effects and patient compliance of these two groups were compared. Eradication efficacy was determined by 13 C urea breath test (13 C UBT) 4-8 weeks after finishing treatment. Antibiotic resistance was determined by the Epsilometer testing (E-test) method. RESULTS: The eradication rates for the HDDT and ACBQT groups were 71.0% and 74.7% (P = .552) by per-protocol analysis, and 65.7% and 68.5% (P = .664) by intention-to-treat analysis. The overall adverse event rates in the HDDT and ACBQT groups were 2.0% and 43.4% (P < .001), respectively. The resistance rates to amoxicillin, clarithromycin, tetracycline, levofloxacin and metronidazole were 15.2%, 42.0%, 5.4%, 35.7% and 83.0%, respectively. Amoxicillin resistance and delta over baseline (DOB) of 13 C UBT ≥ 20 before treatment significantly reduced the eradication rate in 112 participants with H. pylori cultured. CONCLUSION: The HDDT as first-line treatment for H. pylori was unsatisfactory in Gansu. Amoxicillin resistance and DOB of 13 C UBT ≥ 20 before treatment were significantly correlated with H. pylori eradication failure.

Effects of Quadruple Therapy Combined with Probiotics on Helicobacter Pylori-Related Peptic Ulcer.

The present study was designed to observe the effect of quadruple therapy combined with probiotics on Helicobacter pylori-related peptic ulcer. The patients in the control group (n = 90) were given regular quadruple therapy including proton pump inhibitor ilaprazole enteric-coated tablet + two antibiotics amoxicillin dispersible tablet and metronidazole tablet + colloidal bismuth pectin capsule for 2 weeks. Patients in the study group (n = 90) were given abovementioned quadruple therapy combined with probiotics live combined Bifidobacterium, Lactobacillus, and Enterococcus Capsules, oral for 2 weeks. Then Hp clearance rate, recurrence rate, levels of gastrointestinal hormone makers, and advance reactions between two groups were compared. At the 2nd week after the treatment, the Helicobacter pylori clearance rate in the study group (87.79%) was significantly higher than the control group (78.89%), and the total recurrence rate in the study group (6.67%) was significantly lower than the control group (13.33%) (P < 0.05). Serum gastrin and motilin expression were lower, and somatostatin expressions was significantly higher than those in the control group (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). In summary, quadruple therapy combined with probiotics in the treatment of Helicobacter pylori-related peptic ulcer can improve the Helicobacter pylori clearance rate, reduce the Helicobacter pylori recurrence rate, and is beneficial to improving the level of gastrointestinal hormones, with certain safety.

Tailoring bismuth-based nanoparticles for enhanced radiosensitivity in cancer therapy.

Achieving a complete response to cancer treatment is a severe challenge, and has puzzled humans for a long time. Fortunately, radiotherapy (RT) gives rise to a common clinical treatment method, during which the usage of radiosensitizers is essential. Among preclinical radiosensitizers, bismuth-based nanoparticles (Bi-based NPs) are widely explored in cancer diagnosis and treatment, because they share favourable properties, such as low toxicity, strong X-ray absorption and facile preparation. However, pure Bi alone cannot achieve both efficient and safe RT outcomes, mainly due to poor targeting of tumor sites, long retention-induced systemic toxicity and immune resistance. This work provides an overview of recent advances and developments in Bi-based NPs that are tailored to enhance radiosensitivity. For the fabrication process, surface modification of Bi-based NPs is essential to achieve tumor-targeted delivery and penetration. Moreover, the incorporation of other elements, such as Fe ions, can increase diagnostic accuracy with optimal theranostic efficacy. Meanwhile, the structure-activity relationship can also be manipulated to maximize the chemotherapeutic drug loading capability of Bi-based NPs, to enhance X-ray attenuation by means of a large surface area or to achieve safer metabolic routes with rapid clearance from the human body. In addition, Bi-based NPs exhibit synergistic antitumor potential when combined with diverse therapies, such as photothermal therapy (PTT) and high-intensity focused ultrasound (HIFU). To summarize, the latest research on Bi-based NPs as radiosensitizers is described in the review, including both their advantages and disadvantages for improving treatment, thus providing a useful guide for future clinical application.

A Bi2S3-embedded gellan gum hydrogel for localized tumor photothermal/antiangiogenic therapy.

An injectable gellan gum-based nanocomposite hydrogel (Bi2S3@GG) was designed for X-ray computed tomography (CT) imaging and photothermal/antiangiogenic therapy. The linear anionic polysaccharide gellan gum (GG) was used as a stabilizer, embedded with ultra-small bismuth sulfide (Bi2S3) nanodots (∼2 nm) through a one-pot synthesis method. The as-prepared Bi2S3@GG hydrogel displays excellent capability for both photothermal therapy (PTT) (with a photothermal conversion efficiency of 44.3%) and X-ray computed tomography (with an X-ray absorption coefficient of 51.5 HU L g-1), integrated with real-time monitoring drug retention and tunable therapeutic functions. After the incorporation of sorafenib (SF), the hydrogel shows a sustained release of SF over 15 days. A tumor suppression rate of 98.2% is shown at day 22 postinjection in the mice received the combined treatments of photothermal/antiangiogenic therapy. In contrast, tumor growth and recurrence are observed in the single treatment. Our work presents a new strategy to construct a multifunctional hydrogel platform for a safe and precise antitumor therapy.

Pnictogens in medicinal chemistry: evolution from erstwhile drugs to emerging layered photonic nanomedicine.

Pnictogens (the non-metal phosphorus, metalloids arsenic and antimony, and metal bismuth) possess diverse chemical characteristics that support the formation of extended molecular structures. As witnessed by the centuries-old (and ongoing) clinical utilities, pnictogen-based compounds have secured their places in history as "magic bullet" therapeutic drugs in medicinal contexts. Moreover, with the development of recent metalloproteomics and bio-coordination chemistry, the pnictogen-based drugs functionally binding to proteins/enzymes in biological systems have been underlaid for "drug repurposing" with promising opportunities. Furthermore, advances in the modern materials science and nonotechnology have stimulated a revolution in other newly discovered forms of pnictogens-phosphorene, arsenene, antimonene, and bismuthine (layered pnictogens). Based on their favorable optoelectronic properties, layered pnictogens have shown dramatic superiority as emerging photonic nanomedicines for the treatment of various diseases. This tutorial review outlines the history and mechanism of action of ancient pnictogen-based drugs (e.g., arsenical compounds in traditional Chinese medicine) and their repurposing into modern therapeutics. Then, the revolutionary use of emerging layered pnictogens as photonic nanomedicines, alongside assessments of their in vivo biosafety, is discussed. Finally, the challenges to further development of pnictogens are set forth and insights for further exploration of their appealing properties are offered. This tutorial review may also provide some deep insights into the fields of integrated traditional Chinese and Western medicines from the perspective of materials science and nanotechnology.

Effects of bismuth subsalicylate and encapsulated calcium-ammonium nitrate on enteric methane production, nutrient digestibility, and liver mineral concentration of beef cattle.

Two randomized block designs were performed to evaluate the effects of bismuth subsalicylate (BSS) and encapsulated calcium-ammonium nitrate (eCAN) on enteric methane production, nutrient digestibility, liver mineral concentration, and performance of beef cattle consuming bahiagrass hay (Paspalum notatum; ad libitum) and sugar cane molasses [1.07 kg/d; dry matter basis]. Experiment 1, used 25 crossbred steers [335 ± 46 kg of initial body weight (BW)] with a 2 × 2 + 1 factorial arrangement of treatments for two 20 d periods. Factors were nonprotein nitrogen (NPN) source (350 mg/kg BW of nitrate or 182 mg/kg BW of urea), BSS (0 or 58.4 mg/kg BW), and a negative control (NCTRL; bahiagrass hay and molasses only). Steers were re-randomized for a second period (n = 10/treatment total). Intake, apparent total tract digestibility and enteric methane were evaluated. Experiment 2 used 75 crossbred heifers in 25 pens (3 heifers/pen; 279 ± 57 kg of initial BW), consuming the same diet and treatments as experiment 1, to determine liver mineral concentration and growth performance over 56 d. Orthogonal contrasts were used to evaluate the effects of NPN (NCTRL vs. others), source of NPN (NS; urea vs. eCAN), BSS, and NS × BSS. For experiment 1, no interactions were observed for any variables, nor were there any effects of NPN on total tract digestibility of nutrients, except for crude protein. Digestibility of all nutrients was reduced (P ≤ 0.021) for steers consuming eCAN compared with urea. There was no effect (P > 0.155) of BSS on digestibility of nutrients; however, BSS reduced (P = 0.003) apparent S retention. Enteric CH4 emission (g/kg BW0.75) was decreased (P = 0.051) by 11% with the addition of eCAN compared with urea. For experiment 2, no NS × BSS interactions (P ≥ 0.251) were observed to affect liver mineral concentration; however, the addition of BSS decreased liver concentration of Cu (P = 0.002) while increasing Fe concentration (P = 0.016). There was an NS × BSS interaction (P = 0.048) where heifers consuming eCAN and BSS had lesser final BW compared with heifers consuming urea and BSS. While eCAN may be a viable resource for mitigating enteric CH4 production of forage-fed cattle, the negative effects on digestibility should be considered. Furthermore, BSS, at the amount provided, appears to have no negative effects on digestibility of nutrients in forage-fed cattle; however, there may be deleterious impacts on performance depending upon what nitrogen source is supplied.

Effects of bismuth subsalicylate and encapsulated calcium ammonium nitrate on ruminal fermentation of beef cattle.

A replicated 5 × 5 Latin square design with a 2 × 2 + 1 factorial arrangement of treatments was used to determine the effects of bismuth subsalicylate (BSS) and encapsulated calcium ammonium nitrate (eCAN) on ruminal fermentation of beef cattle consuming bahiagrass hay (Paspalum notatum) and sugarcane molasses. Ten ruminally cannulated steers (n = 8; 461 ± 148 kg of body weight [BW]; average BW ± SD) and heifers (n = 2; 337 ± 74 kg of BW) were randomly assigned to one of five treatments as follows: 1) 2.7 g/kg of BW of molasses (NCTRL), 2) NCTRL + 182 mg/kg of BW of urea (U), 3) U + 58.4 mg/kg of BW of BSS (UB), 4) NCTRL + 538 mg/kg of BW of eCAN (NIT), and 5) NIT + 58.4 mg/kg of BW of BSS (NITB). With the exception of NCTRL, all treatments were isonitrogenous. Beginning on day 14 of each period, ruminal fluid was collected and rectal temperature was recorded 4× per day for 3 d to determine ruminal changes every 2 h from 0 to 22 h post-feeding. Ruminal gas cap samples were collected at 0, 3, 6, 9, and 12 h on day 0 of each period followed by 0 h on days 1, 2, 3, and 14. Microbial N flow was determined using Cr-Ethylenediaminetetraacetic acid, YbCl3, and indigestible neutral detergent fiber for liquid, small particle, and large particle phases, respectively. Data were analyzed using the MIXED procedure of SAS. Orthogonal contrasts were used to evaluate the effects of nonprotein nitrogen (NPN) inclusion, NPN source, BSS, and NPN source × BSS. There was no treatment effect (P > 0.05) on concentrations of H2S on day 0, 1, 2, or 14; however, on day 3, concentrations of H2S were reduced (P = 0.018) when NPN was provided. No effect of treatment (P = 0.864) occurred for ruminal pH. There was an effect of NPN source on total concentrations of VFA (P = 0.011), where a 6% reduction occurred when eCAN was provided. There were effects of NPN (P = 0.001) and NPN source (P = 0.009) on the concentration of NH3-N, where cattle consuming NPN had a greater concentration than those not consuming NPN, and eCAN reduced the concentration compared with urea. Total concentrations of VFA and NH3-N were not affected (P > 0.05) by BSS. There was an effect of BSS (P = 0.009) on rectal temperature, where cattle not consuming BSS had greater temperatures than those receiving BSS. No differences for NPN, NPN source, nor BSS (P > 0.05) were observed for microbial N flow. In conclusion, eCAN does not appear to deliver equivalent ruminal fermentation parameters compared with urea, and BSS has limited effects on fermentation.

Effects of addition of probiotic and/or bismuth to triple therapy of H. pylori and analysis of genetic variation of 23S rRNA gene between patients with clarithromycin sensitivity and resistance.

The aim of the study was to compare the effects of three treatment regimens for H. pylori in patients sensitive to clarithromycin and analyze the polymorphism of 23S rRNA gene between patients who were sensitive or resistant to clarithromycin in a Chinese Han population. 204 H. pylori sensitive cases and 45 H. pylori resistant Han patients were selected as subjects of the research. All H. pylori sensitive cases were divided into three groups based on their different therapies. The polymerase chain reaction-ligase detection reaction (PCR) was used to identify the genotype at the A2143G of the 23S rRNA gene. SPSS18.0 software was applied to analyze the data statistically. The success rate of H. pylori eradication in the TTP (TT + probiotic) group was higher when compared with the triple therapy (TT) group, and the difference was statistically significant. The incidence of abdominal pain, headache and diarrhea in TTP group was significantly lower than that in the TT group and the TTB (TT+ bismuth) group. Moreover, patients in the TTP group suffered less taste impairment than patients in the other two groups. In addition, there was significant difference in genotype frequency distribution between the clarithromycin-resistant group and the clarithromycin-sensitive group. It was suggested in the results of Chinese Han population that the TTP regimen was significantly superior to the other two regimens in the treatment of clarithromycin-sensitive H.PYLORI infection. In addition, potential genotypic differences between clarithromycin-sensitive and drug-resistant patients provided a theoretical basis for gene therapy in patients with clarithromycin resistance.

Facile green synthesis of bismuth sulfide radiosensitizer via biomineralization of albumin natural molecule for chemoradiation therapy aim.

High atomic number Z, nanoparticles are able to enhance the photoelectric and Compton effects under X-Ray irradiation resulting the increase of radiation therapy efficacy. To achieve enhanced radiation therapy, Bi2S3 biocompatible particles coated with bovine serum albumin (BSA) (Bi2S3@BSA HNPs) were prepared through a BSA-mediated biomineralization procedure under green conditions. Then, to achieve improved chemo-radiation therapy against HT-29 cancer cells, curcumin (CUR) as natural anti-cancer therapy agent loaded on the Bi2S3@BSA (Bi2S3@BSA@CUR HNPs). Next, this synthesized nanodrug was evaluated for physical and chemical properties and in vitro cytotoxicity studies. Here, in vitro enhanced chemo-radiation combination therapy power was evaluated against HT-29 cell line under 2 Gy and 6 Gy X-ray irradiation doses. The Bi2S3@BSA HNPs without irradiation rarely affect cell viability which shown the non-toxicity of Bi2S3@BSA HNPs. The result of this study proved that Bi2S3@BSA@CUR HNPs can be used as both proficient vehicles for effective delivery of CUR and radiosensitizer in the treatment of cancer. In addition, the result of this study confirmed that the combination of high Z-element nanoradiosensitizer, Bi2S3@BSA HNPs, with a natural anti-cancer drug, CUR, enhanced therapeutic power against HT-29 cells.

Platelet-membrane-camouflaged bismuth sulfide nanorods for synergistic radio-photothermal therapy against cancer.

Bismuth-containing nanoparticles (BNPs) are potential enhancers for tumor radiotherapy. Improving the bioavailability and developing synergistic therapeutic regimens benefit the drug transformation of BNPs. In the present study, we prepare a mesoporous silica-coated bismuth nanorod (BMSNR) camouflaged by a platelet membrane (PM). This biomimetic material is termed BMSNR@PM. The PM camouflage enhances the immune escape of the BMSNRs by lowering endocytosis by macrophages in the reticuloendothelial system. Additionally, the PM camouflage strengthens the material tumor-targeting capacity and leads to better radiotherapeutic efficacy compared with bare BMSNRs. Owing to the photothermal effect, BMSNR@PMs alters the cell cycle of 4T1 cancer cells post-treatment with 808 nm near-infrared irradiation (NIR). The proportions of S phase and G2/M phase cells decrease and increase, respectively, which explains the synergistic effect of NIR on BMSNR@PM-based radiotherapy. BMSNR@PMs efficiently eradicates cancer cells by the combined action of photothermal therapy (PTT) and radiotherapy in vivo and markedly improves the survival of 4T1-tumor-bearing mice. The synergistic therapeutic effect is superior to the outcomes of PTT and radiotherapy performed alone. Our study demonstrates a versatile bismuth-containing nanoplatform with tumor-targeting, immune escape, and radiosensitizing functionalities using an autologous cell membrane biomimetic concept that may promote the development of radiotherapy enhancers.

Antimicrobial and anti-biofilm activities of Bi subnitrate and BiNPs produced by Delftia sp. SFG against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis.

In the present study Delftia sp. Shakibaie, Forootanfar, and Ghazanfari (SFG), was applied for preparation of biogenic Bi nanoparticles (BiNPs) and antibacterial and anti-biofilm activities of the purified BiNPs were investigated by microdilution and disc diffusion methods. Transmission electron micrographs showed that the produced nanostructures were spherical with a size range of 40-120 nm. The measured minimum inhibitory concentration of both the Bi subnitrate and BiNPs against three biofilms producing bacterial pathogens of Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis were found to be above 1280 µg/ml. Addition of BiNPs (1000 µg/disc) to antibiotic discs containing tobramycin, nalidixic acid, ceftriaxone, bacitracin, cefalexin, amoxicillin, and cefixime significantly increased the antibacterial effects against methicillin-resistant S. aureus (MRSA) in comparison with Bi subnitrate (p < 0.05). Furthermore, the biogenic BiNPs decreased the biofilm formation of S. aureus, P. aeruginosa, and P. mirabilis to 55, 85, and 15%, respectively. In comparison to Bi subnitrate, BiNPs indicated significant anti-biofilm activity against P. aeruginosa (p < 0.05) while the anti-biofilm activity of BiNPs against S. aureus and P. mirabilis was similar to that of Bi subnitrate. To sum up, the attained results showed that combination of biogenic BiNPs with commonly used antibiotics relatively enhanced their antibacterial effects against MRSA.

Risk factors of rescue bismuth quadruple therapy failure for Helicobacter pylori eradication.

BACKGROUND AND AIM: Failure of bismuth quadruple therapy for Helicobacter pylori eradication is frequently observed. To increase the eradication rate, comprehensive analyses need to be performed regarding risk factors of bismuth quadruple therapy failure based on complete standard culture and antimicrobial susceptibility testing results. METHODS: Patients with history of failed first therapy who had H. pylori colonies isolated from culture and successful minimum inhibitory concentration (MIC) test were enrolled. Esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapies for 7 or 14 days were given. Eradication rate, treatment compliance, adverse events, and risk factors for the failure of bismuth quadruple therapy were analyzed. RESULTS: A total 54 patients were enrolled. Overall eradication rate in the present study was 88.8%. The eradication rate for cases with metronidazole resistance such as MIC 8-16 µg/mL or 16-32 µg/mL was 92.8% (13/14). For cases with high level metronidazole resistance (MIC > 32 µg/mL), the eradication rate was only 60% (6/10). Multivariate analysis regarding compliance, treatment duration, age > 60, three kinds of metronidazole MICs, tetracycline MIC > 4 µg/mL, adverse events and any other parameters, "metronidazole resistance, high level (MIC > 32 µg/mL)" was the only independent risk factor for eradication failure (P = 0.007). CONCLUSION: For cases with metronidazole resistance at MIC > 32 µg/mL, rescue therapy other than bismuth-containing quadruple therapy is needed.

Iron oxide/bismuth oxide nanocomposites coated by graphene quantum dots: "Three-in-one" theranostic agents for simultaneous CT/MR imaging-guided in vitro photothermal therapy.

BACKGROUND: The all-in-one nanoprobes (NPs) have drawn biomedical attention in the cancer therapy field due to simultaneously combing the capabilities of therapeutic and diagnostic methods into a single nanoprobe. METHOD: In this study, we developed a theranostic probe based on superparamagnetic iron oxide (SPIO) and bismuth oxide (Bi2O3) with graphene quantum dots (GQDs) coating to investigate the physical properties for in vitro CT/MR dual-modal biomedical imaging and cancer-specific photothermal therapy (PTT). RESULT: The GQDs-Fe/Bi nanocomposites showed strong light absorbance profile with wide-band in the near-infrared region, without any sharp peak or decline. The highest photo-to-thermal conversion efficacy (η), was found to be 31.8% with the high photostability upon the irradiation of NIR 808-nm laser. The results of in vitro photothermal ablation of cancerous cells demonstrated that the cells significantly killed in the presence of NPs (∼53.4%) with a dose-dependent manner in comparison to only laser group (3.0%). In GQDs-Fe/Bi nanocomposites, Bi with a high atomic number (Z = 83) exhibited a superior X-ray attenuation capability (175%) than the clinical CT agent-used dotarem, also, SPIO with excellent magnetization property showed strong T2-relaxation shortening capability (r2 = 62.34 mM-1.s-1) as a contrast agent for CT/MR imaging. CONCLUSION: Our results demonstrate that the developed NPs can incorporate dual-modality imaging capability into a photo absorber for CT/MR imaging-guided tumor PTT.

Antimicrobial effect of bioceramic cements on multispecies microcosm biofilm: a confocal laser microscopy study.

OBJECTIVES: To assess the viability of multispecies microcosm biofilm after contact with NeoMTA Plus, Biodentine, and MTA Angelus. MATERIALS AND METHODS: Fifty-four human dentin blocks (4 × 5 × 4 mm) were allocated to Hawley retainers, worn by six volunteers for 72 h. The blocks were then individually incubated in BHI broth for 21 days at 37 °C. At the end of experimental time for biofilm growth, the samples were randomly divided into four groups (n = 12): NeoMTA Plus, Biodentine, MTA Angelus, and negative control. The materials were placed in contact with the blocks. All samples were placed in cell-culture plate wells and incubated in BHI broth for 7 days at 37 °C. One sample from each volunteer (n = 6) was analyzed by SEM to describe the biofilm morphology. CLSM was performed to determine the percentage of viable biofilm biovolume. The data were statistically analyzed by one-way ANOVA and Tukey's multiple comparison test (α = 5%). RESULTS: SEM showed biofilm formed by spherical and rod-shaped bacteria surrounded by an extracellular matrix. No material was able to kill all biofilm cells, and all groups had more than 50% of viable bacteria. NeoMTA Plus was significantly different from the negative control group (P < .05). CONCLUSIONS: All tested materials were not effective against multispecies microcosm biofilm. CLINICAL RELEVANCE: NeoMTA Plus, Biodentine, and MTA Angelus were not effective against multispecies microcosm biofilm. It is essential to understand that these bioceramic cements are indicated for infected clinical situations. Thus, complementary disinfection procedures should be conducted prior to filling with these materials.

Laser-Induced Transformable BiS@HSA/DTX Multiple Nanorods for Photoacoustic/Computed Tomography Dual-Modal Imaging Guided Photothermal/Chemo Combinatorial Anticancer Therapy.

Suboptimal intratumor accumulation and poorly controllable release of encapsulated drugs remain unresolved challenges hampering further advancement of nanomedicines in cancer therapy. Herein, we conceived near-infrared (NIR) laser-triggered transformable BiS@HSA/DTX multiple nanorods (mNRs), which were made of small bundles of bismuth sulfide nanorods (BiS NRs) coated with docetaxel (DTX)-inlaid human serum albumin (HSA). The BiS@HSA/DTX mNRs had a lateral size of approximately 100 nm and efficiently accumulated in the tumor microenvironment upon systemic administration in tumor-bearing nude mice. NIR laser irradiation of the tumor area caused rapid disassembly of the BiS@HSA/DTX mNRs into individual HSA-coated BiS nanorods (BiS@HSA iNRs) and triggered the release of DTX from the HSA corona, due to the local temperature increase generated by BiS NRs via the photothermal effect. The laser-induced transformation into BiS@HSA iNRs facilitated their penetration and increased the retention time in tumor. The spatiotemporal delivery behavior of the BiS@HSA/DTX mNRs could be monitored by photoacoustic/computed tomography dual-modal imaging in vivo. Furthermore, because of the excellent photothermal conversion properties of BiS NRs and laser-triggered DTX release from BiS@HSA/DTX mNRs, efficient tumor combinatorial therapy was achieved via concurrent hyperthermia and chemotherapy in mice treated with BiS@HSA/DTX mNRs upon NIR laser irradiation.

Fabrication of PEGylated Fe@Bi2S3 nanocomposites for dual-mode imaging and synergistic thermoradiotherapy.

Nanocomposites for integrating imaging and therapy have attracted tremendous attention for biomedical applications. Herein, Fe@Bi2S3 nanocomposites modified with polyethylene glycol (PEG) molecules are fabricated for synergistic thermoradiotherapy. For such nanocomposites, Bi2S3 exhibits a strong absorbance in the near-infrared (NIR) region, which allows Bi2S3 to convert energy from light into heat for effective photothermal therapy (PTT), whereas Bi can also significantly enhance radio-mediated cell death induction as a radiotherapy sensitizer due to its high atomic number (high-Z). Most importantly, it is found that the combination of PTT and radiation therapy (RT), using PEGylated Fe@Bi2S3 nanocomposites, can bring a strong synergistic effect for the tumor treatment in in vitro and in vivo experiments. Besides, the magnetic Fe core and the Bi2S3 shell components endow this nanocomposite with an ability to serve as both a magnetic resonance imaging (MRI) and computed tomography (CT) contrast agent. Therefore, our work presents a new type of multifunctional nanocomposite with the potential for synergistic thermoradiotherapy and simultaneously MRI/CT imaging.

Rapid synthesis of Bi2O3 nano-needles via 'green route' and evaluation of its anti-fungal activity.

Here, the authors report a rapid, simple, and eco-friendly process for synthesis of Bi2O3 nano-needles. Dioscorea alata tuber extract was used as both reducing and capping agent for the first time. These nanoparticles were characterised by X-ray diffraction, field emission scanning electron microscope, and Fourier transform infrared (FTIR) spectrometry, the nano-structured Bi2O3 needles have an average diameter of 158 nm with the lengths in the range of 1-3 µm. CLSI M27-A2 standard was followed for evaluation of anti-fungal activity. Bi2O3 nano-needles show remarkable activity against Candida albicans. It exhibits four time greater activity than bulk Bi2O3 powder and two time greater activity than itraconazole, which makes it a potent anti-fungal drug.

Bismuth antimicrobial drugs serve as broad-spectrum metallo-ß-lactamase inhibitors.

Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-ß-lactamases (MBLs), e.g., New Delhi metallo-ß-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.

One-pot synthesis of AIE based bismuth sulfide nanotheranostics for fluorescence imaging and photothermal therapy.

Photothermal therapy (PTT) has been widely investigated as a minimally invasive strategy for cancer therapy due to its favorable biosafety. Nevertheless, there is only limited success in the exploration of nanotheranostics composing of both fluorescent dyes and PTT agents since their fluorescence would always be quenched. Herein, a facile one-pot synthesis approach of Aggregation Induced Emission (AIE) based Bi2S3 nanotheranostics is described, and their effectiveness for fluorescence imaging and simultaneous PTT has been demonstrated. AIE incorporated BSA was employed for the biomineralization synthesis of Bi2S3 nanoparticles (NPs), which endowed as-prepared BSA-PhENH2-Bi2S3 NPs with excellent biocompatibility and ultrasmall size. Moreover, the resulted NPs also exhibited remarkable photothermal effect and photostability. Importantly, BSA-PhENH2-Bi2S3 NPs could efficiently get into HepG2 cells, and light their cytoplasm region with bright fluorescence owning to the superb fluorescence property of AIE, which could simultaneously prompt cancer cells death under an 808nm laser irradiation. This work provides a universal approach for the fabrication of AIE based nanotheranostics via albumin-mediated biomineralization method, and the as-prepared BSA-PhENH2-Bi2S3 NPs possess great potential for cancer theranostics.