Pseudomonas aeruginosa (P. aeruginosa) is a common pathogen isolated from patients with nosocomial infections. Due to its intrinsic and acquired antimicrobial resistance, limited classes of antibiotics can be used for the treatment of infection with P. aeruginosa. Of these, the carbapenems are very important; however, the occurrence of carbapenem-resistant strains is gradually increasing over time. Deficiency of the outer membrane protein OprD confers P. aeruginosa a basal level of resistance to carbapenems, especially to imipenem. Functional studies have revealed that loops 2 and 3 in the OprD protein contain the entrance and/or binding sites for imipenem. Therefore, any mutation in loop 2 and/or loop 3 that causes conformational changes could result in carbapenem resistance. OprD is also a common channel for some amino acids and peptides, and competition with carbapenems through the channel may also occur. Furthermore, OprD is a highly regulated protein at transcriptional and post-transcriptional levels by some metals, small bioactive molecules, amino acids, and efflux pump regulators. Because of its hypermutability and highly regulated properties, OprD is thought to be the most prevalent mechanism for carbapenem resistance in P. aeruginosa. Developing new strategies to combat infection with carbapenem-resistant P. aeruginosa lacking OprD is an ongoing challenge.

Background The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis. Methods A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected. Results On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells. Conclusions A sustained decrease in lymphocyte subsets, especially CD4+ T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.

Circulating procalcitonin (PCT) is a biomarker that can be used in diagnosing bacterial infections. We performed a quantitative meta-analysis of available randomized controlled trials to determine whether antibiotic therapy based on PCT measurements alters clinical outcomes and antibiotic use in patients with lower respiratory tract infections. We identified studies through MEDLINE (1996 to 2010), the ISI Web of Knowledge (1996 to 2010), and Ovid. Studies that met our criteria were prospective, randomized controlled trials involving patients with respiratory tract infections. Outcomes of mortality, intensive care unit (ICU) admission, length of hospital stay, number of antibiotic prescriptions, and duration of antibiotic treatment were evaluated. Eight studies randomizing 3,431 patients met our criteria for inclusion. Pooled analysis showed a significant reduction in number of antibiotic prescriptions and duration of antibiotic use in patients with PCT-guided antibiotic treatment compared to standard therapy. In addition, the use of PCT-guided antibiotic therapy did not impact mortality, ICU admission, or length of hospital stay in these studies. A high degree of heterogeneity was identified in 3 of 5 outcomes that were evaluated, and sensitivity analysis indicated that heterogeneity was decreased among studies using the same PCT-based treatment algorithm. In conclusion, PCT-guided antibiotic therapy in patients with respiratory tract infections appears to reduce antibiotic use without affecting overall mortality or length of stay in the hospital.

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The coronavirus disease 2019 is a new type of pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. COVID-19 is affecting millions of patients, and the infected number keeps increasing. SARS-CoV-2 is highly infectious, has a long incubation period, and causes a relatively high death rate, resulting in severe health problems all over the world. Currently there is no effective proven drug for the treatment of COVID-19; therefore, development of effective therapeutic drugs to suppress SARS-CoV-2 infection is urgently needed. In this review, we first summarize the structure and genome features of SARS-CoV-2 and introduce its infection and replication process. Then, we review the clinical symptoms, diagnosis, and treatment options of COVID-19 patients. We further discuss the potential molecular targets and drug development strategies for treatment of the emerging COVID-19. Finally, we summarize clinical trials of some potential therapeutic drugs and the results of vaccine development. This review provides some insights for the treatment of COVID-19.The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now affecting millions of patients all over the world as of May 30, 2020. 1,2 According to World Health Organization (WHO) statistics on March 3, the mortality rate among confirmed COVID-19 cases was 3.4%. As of May 22, according to Worldometer, the mortality rate is nearly 5.9%. In Italy, however, the mortality rate is more than 13%. The SARS-CoV-2 coronavirus is a type of single-stranded RNA virus that belongs to the coronaviruses family. [2][3][4] Coronaviruses can be divided into four genera: Alphacoronavirus (aCoV), Betacoronavirus (bCoV), Gammacoronavirus (gCoV), and Deltacoronavirus (dCoV). 5 Currently, seven coronaviruses are known to infect human, including two alphacoronaviruses (HCoV-229E and HKU-NL63) and five betacoronaviruses (HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2). During the past two decades, three previously unknown betacoronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2) have emerged. 6 These deadly coronaviruses cause lower respiratory tract infections, resulting in acute pneumonia, respiratory distress, cytokine storms, multiple organ dysfunctions, and even patient death. 1,7,8 In this review, we highlight the pandemic of the emerging COVID-19, review the key molecular and clinical characteristics of SARS-CoV-2, and discuss the potential options for developing drugs for the treatment of COVID-19. Genomic Structure and Viral Protein Characteristics of SARS-CoV-2The genome of SARS-CoV-2 contains 29,903 nt (NCBI: NC_045512.2), of which the GC content is 38%. The SARS-CoV-2 genome encodes about 9,860 aa. Similar to other coronaviruses, the SARS-CoV-2 genome consists of two flanked untranslated regions (UTRs), a 5 0 long open reading frame (ORF1a/b) that encodes polyproteins, and several structural protein-encoding ORFs (Figure 1). [9][10][11] The polyprotein encoded by 5 0 ORF1a/b is cleaved...

miR-101–3p may play a therapeutic role in various tumours. However, its anti-tumour mechanism remains unclear, and a definitive strategy to treat tumour cells in vivo is lacking. The objective of this study was to investigate the inhibitory mechanism of miR-101–3p on tumour cells and to develop relevant nanomedicines for in vivo therapy. The expression levels of miR-101–3p and its target protein TBLR1 in tumour tissues and cells were detected, and their relationship with ferroptosis was clarified. Furthermore, the efficacy of nanocarriers in achieving in vivo therapeutic gene delivery was evaluated. Nanomedicine was further developed, with the anti-proliferative in vivo therapeutic effect validated using a subcutaneous xenograft cancer model. The expression level of miR-101–3p negatively correlated with clinical tumour size and TNM stage. miR-101–3p restores ferroptosis in tumour cells by directly targeting TBLR1, which in turn promotes apoptosis and inhibits proliferation. We developed nanomedicine that can deliver miR-101–3p to tumour cells in vivo to achieve ferroptosis recovery, as well as to inhibit in vivo tumour proliferation. The miR-101–3p/TBLR1 axis plays an important role in tumour ferroptosis. Nanopharmaceuticals that increase miR-101–3p levels may be effective therapies to inhibit tumour proliferation.

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Previous studies indicated that Campylobacter has developed several mechanisms that confer resistance to florfenicol, which is used in food animal production. This study describes the coexistence of optrA and fexA in Campylobacter jejuni and Campylobacter coli isolates from pigs and poultry. Moreover, whole-genome sequencing data showed that the two genes are located in various multidrug resistance genomic islands within different regions of the Campylobacter genomes. The emergence of optrA and fexA may support the spread of florfenicol-resistant Campylobacter strains of animal origin. IMPORTANCE Florfenicol is widely used for the treatment of respiratory infections and as a feed additive in food animal production. As a foodborne pathogen, Campylobacter is constantly exposed to florfenicol, and resistance to this antimicrobial agent has increased in recent years. Previous studies indicated that Campylobacter has developed several mechanisms that confer resistance to florfenicol. This study describes for the first time the coexistence of the florfenicol exporter FexA and the ribosomal protective protein OptrA in Campylobacter jejuni isolated from pigs. The two genes were located in various multidrug resistance genomic islands within different regions of the Campylobacter genomes. Although phenicols are not commonly used for the treatment of Campylobacter infections, the extensive use of florfenicol in food animals may play a role in the coselection of multidrug resistance genomic island (MDRGI)-carrying Campylobacter isolates which also exhibited resistance to critically important antimicrobial agents (macrolides, aminoglycosides, and tetracyclines) commonly used for the treatment of human campylobacteriosis.