Microbial natural product is an important source for drug discovery. As more and more microbial genomes are sequenced, bioinformatics analysis shows that there are huge resources of novel natural products. Genome mining is a new strategy of natural product discovery based on gene cluster sequences and biosynthetic pathways. At the same time, it can directly associate the structures of natural products with synthetic pathways, and facilitate the study of biosynthesis and combinatorial biosynthesis. In this paper, the strategies of genome mining, including bioinformatics predictions, metabolomic comparisons and genetic manipulations, are reviewed, which shows a great advantage of this strategy in exploiting the potential of microbial natural products. With the development of genome mining methodology and techniques, it will be possible to realize rational exploitation of microbial natural product resources.
Acne vulgaris (AV) is the familiar chronic skin ailment affecting most of the individuals. This multifarious, disease involves the bacterium gram-positive, anaerobic Propionibacterium acnes (P. acnes) which resides on skin microflora, and participated in acne inflammation and acne lesions. The object of this review is to discuss presently available in vitro, ex vivo, and in vivo models to evaluate the cosmetic formulations that are developed for dealing and prevention of acne formation. These various available models offer new chances for further research on biologically active materials, drugs & pharmaceutical as well as cosmetics for acne treatment.
Plant invasion is one of the major threats to natural ecosystems. The alligator weed grows rapidly within a small span of time and is easily available all over the world. β-Carboline and quercetin are considered as excellent bioactive components of the alligator weed. In our study LC-MS/MS methods were performed for the detection and determination of the bioactive constituents, ꞵ-carboline and quercetin in leaves, in multiple reaction monitoring (MRM) mode. The effects of methanol extract on cardiomyocyte apoptosis induced by doxorubicin using H9c2 cells were evaluated by MTT assay and Annexin V-FITC/PI staining assay. A sensitive and selective liquid chromatography tandem mass spectrometry was developed and validated for the determination of ꞵ-carboline and quercetin in this plant. According to in vitro cell evaluation experiments, methanol extracts significantly prevented cardiomyocyte apoptosis induced by doxorubicin.
Controlled release microparticles in a sub-gram-scale batch were fabricated using a ball mill, dry coating technique, to coat the water-soluble core material. This process also guaranteed the maintenance of the containment's integrity during the dry coating process. Quinine (average diameter, ca. 10 μm) and carnauba wax were used as the core and coating material, respectively. We evaluated the influence of process time, milling speed, and quinine-to-carnauba wax ratio on the particle size of the coated particles and their in vitro drug release profiles. Scanning electron microscopic observations suggested that the small wax particles attached to the core (quinine) particles resulted in a smooth film during the dry coating process. The size distribution of the coated particles agreed with the theoretically estimated size distribution. The in vitro release test demonstrated that the coated particles released quinine over 2 h in a biphasic mode. These results suggest that dry coating of microparticles less than 50 µm (D99) is feasible on a several-grams-batch scale. This new ball mill-coating technique also enables a guaranteed containment, a prerequisite for the manufacturing of highly bioactive or biohazard substances.
Injury of the insect body wall, which enables environmental microorganisms to invade into insect tissues, induces innate immune responses including the induction of antimicrobial peptides (AMPs) in flies and silkworms. Here, house fly (Musca domestica) larvae and pupae were injured using a needle and the effects on the expression of genes encoding AMPs were examined. The expression of AMP genes including defensin, attacin, diptericin, and sarcotoxin II dramatically increased in both larvae and pupae after injury of the body wall, indicating that innate immune responses were induced. Furthermore, the injury-dependent expression of AMP genes was examined in larval tissues including fat bodies, hemocytes, salivary glands, and digestive tracts. Injury-dependent AMP gene expression was observed in salivary glands, hemocytes, and fat bodies, but not in digestive tracts. The degree of the transcriptional induction of each gene differed among tissues, suggesting that their expression is governed by complex regulatory machinery and that AMPs have tissue-specific functions. To further examine the properties of the AMPs, we examined the antimicrobial activities of partial synthetic peptides corresponding to portions of the predicted AMP proteins deduced from the AMP genes. A synthetic peptide exhibited antimicrobial activity, indicating that these injury-inducible genes are potential medicinal resources.
Invasive fungal infections (IFI) are commonly seen in immunosuppressed individuals but their epidemiology in critically ill patients has not been well described. The aim of this study was to determine the frequency, risk factors and outcome of invasive fungal infections in a medical intensive care unit. A prospective observational study was carried out between August 2016 and March 2018 in the medical intensive care unit. Patients above the age of 14 years with endotracheal intubation and/or central venous catheter for at-least three days and sepsis (not responding to 48 hours of intravenous antibiotic therapy) were included in the study. Suitable samples were collected and were subjected to fungal diagnostics. Invasive fungal disease was defined according to standard guidelines. Of the 100 recruited patients, a total of 11 patients had invasive aspergillosis, three patients had invasive candidiasis and one patient had both invasive aspergillosis and mucormycosis. IFI was more commonly seen in patients with auto-immune diseases (p = 0.002, odds ratio-10.13 (95% CI: 2.3-44)). A mortality of 73% was observed in patients with IFI. In conclusion, IFI, especially aspergillosis is grossly under-reported in critical settings. Early suspicion, thorough investigation and timely diagnosis may alleviate patients of significant mortality and morbidity.
We aimed to investigate the efficacy and safety of combination of sofosbuvir with ombitasvir, paritaprevir, and ritonavir ± ribavirin as a retreatment option for experienced Egyptian patients who failed previous sofosbuvir, daclatasvir ± ribavirin therapy. A total of 75 treatment-experienced patients were allocated for the completion of their treatment period according to criteria formed by the national committee for control of viral hepatitis. The enrolled patients were followed up throughout treatment, at the end of treatment and 3 months after the end of the treatment by clinical evaluation and laboratory investigations. 27 patients were treated with sofosbuvir with ombitasvir, paritaprevir, and ritonavir plus ribavirin for 12 weeks while 48 patients were treated with sofosbuvir with ombitasvir, paritaprevir, and ritonavir without ribavirin for 24 weeks. The per-protocol sustained virological response at week 12 (SVR12) rate was 100% in both groups while the intention-to-treat SVR12 was 93.4% in all patients, 97.9% in the 24 weeks group and 85.2% in the 12 weeks group. The regimen was well tolerated and the most common adverse effects observed across treatment and during follow-up period included fatigue (38.6%) and headache (29.3%), withdrawal due to adverse effects occurred in 6.6%. We can conclude that retreatment with sofosbuvir with ombitasvir, paritaprevir, and ritonavir ± ribavirin is well tolerated and achieved high SVR12 rates in chronic HCV Egyptian patients with previous sofosbuvir plus daclatasvir treatment failure. Ribavirin free regimen for 24 weeks exerted significant lesser adverse effects.
Mucormycosis is an uncommon aggressive fungal infection usually seen in immunocompromised hosts or patients with burns and trauma. The common presentations include rhino-orbital-cerebral and pulmonary involvement. Osteoarticular involvement is a rare presentation of this disease. We present two cases of osteoarticular mucormycosis of pelvis and long bones of the lower limb, one in a patient with burn injury and other one in a patient with chronic granulomatous disease, hitherto a rarely reported association. Delayed diagnosis in a setting where tuberculosis is a common cause of chronic osteomyelitis, challenges in medical and surgical management of these patients are discussed in this report.
Apremilast is used as a systemic therapy for the treatment of psoriasis and psoriatic arthritis. This drug is considered relatively safe with a very low incidence of serious side effects. Common side effects are diarrhea, nausea, headache, nasopharyngitis, upper respiratory tract infections which are mild to moderate in severity. Diarrhea tends to occur within 2 weeks of starting treatment and resolve spontaneously within 4 weeks without dose adjustment or discontinuation of therapy. Chronic diarrhea and malnutrition due to apremilast have not been reported yet. We report a case of apremilast induced chronic diarrhea leading to malnutrition, necessitating discontinuation of therapy.
The Fukushima research has examined data form a cohort study of 10,000 Japanese children under 18 years old with influenza during three months to demonstrate that the relative risk of A-type abnormal behavior of patients with oseltamivir was 30 times greater than without oseltamivir. By contrast, our research group found that patients who had been administered no neuraminidase inhibitors (NI) or those administered peramivir had higher risk of abnormal behavior than those administered oseltamivir, zanamivir, or laninamivir. A plausible explanation for this gap is that the two studies specifically examined different criteria to report abnormal behavior. In actually, some A-type abnormal behavior might not be life-threatening. Our definition of severe abnormal behavior is better matched to public health concerns and comparison among incidents according to the administered drug is more appropriate as an analytical procedure.