Potential Anti-Mycobacterium tuberculosis Activity of Plant Secondary Metabolites: Insight with Molecular Docking Interactions

Tuberculosis (TB) is a recurrent and progressive disease, with high mortality rates worldwide. The drug-resistance phenomenon of Mycobacterium tuberculosis is a major obstruction of allelopathy treatment. An adverse side effect of allelopathic treatment is that it causes serious health complications. The search for suitable alternatives of conventional regimens is needed, i.e., by considering medicinal plant secondary metabolites to explore anti-TB drugs, targeting the action site of M. tuberculosis. Nowadays, plant-derived secondary metabolites are widely known for their beneficial uses, i.e., as antioxidants, antimicrobial agents, and in the treatment of a wide range of chronic human diseases (e.g., tuberculosis), and are known to “thwart” disease virulence. In this regard, in silico studies can reveal the inhibitory potential of plant-derived secondary metabolites against Mycobacterium at the very early stage of infection. Computational approaches based on different algorithms could play a significant role in screening plant metabolites against disease virulence of tuberculosis for drug designing.

Challenges of stem cell application in research and clinical practice – an update

There are multiple possible applications of stem cells in medicine, from cell-based therapies for degenerative and dystrophic conditions, through novel approaches in cancer treatment, to in vitro organ printing. However, there are still several challenges that need to be overcame before stem cells therapies can be successfully introduced worldwide on a large scale. These include sourcing of stem cells, preventing their aberrant progression and ethical concerns regarding their use in animals and humans. Among the multiple stem cell types present in the human organism from the period of embryonic development to adulthood, this review focuses on the three types that gain the most attention in relation to modern research: embryonic stem cells, induced pluripotent stem cells and adult stem cells. There are a number of obstacles that need to be removed before these cells can be widely applied in clinical practice, including the choice of the perfect source of stem cells, full elucidation of the mechanisms of stem cell differentiation and plasticity, and minimization of adverse side effect potential. Nonetheless, the focus of the scientific community on the topic of stem cells remains unhindered, bringing hope that all of the possible concerns will be addressed in the future.

Human Papillomavirus Vaccine Efficacy and Effectiveness against Cancer

Human papillomavirus (HPV) is the most common sexually transmitted infection, with 15 HPV types related to cervical, anal, oropharyngeal, penile, vulvar, and vaginal cancers. However, cervical cancer remains one of the most common cancers in women, especially in developing countries. Three HPV vaccines have been licensed: bivalent (Cervarix, GSK, Rixensart, Belgium), quadrivalent (Merck, Sharp & Dome (Merck & Co, Whitehouse Station, NJ, USA)), and nonavalent (Merck, Sharp & Dome (Merck & Co, Whitehouse Station, NJ, USA)). The current HPV vaccine recommendations apply to 9 years old and above through the age of 26 years and adults aged 27–45 years who might be at risk of new HPV infection and benefit from vaccination. The primary target population for HPV vaccination recommended by the WHO is girls aged 9–14 years, prior to their becoming sexually active, to undergo a two-dose schedule and girls ≥ 15 years of age, to undergo a three-dose schedule. Safety data for HPV vaccines have indicated that they are safe. The most common adverse side-effect was local symptoms. HPV vaccines are highly immunogenic. The efficacy and effectiveness of vaccines has been remarkably high among young women who were HPV seronegative before vaccination. Vaccine efficacy was lower among women regardless of HPV DNA when vaccinated and among adult women. Comparisons of the efficacy of bivalent, quadrivalent, and nonavalent vaccines against HPV 16/18 showed that they are similar. However, the nonavalent vaccine can provide additional protection against HPV 31/33/45/52/58. In a real-world setting, the notable decrease of HPV 6/11/16/18 among vaccinated women compared with unvaccinated women shows the vaccine to be highly effective. Moreover, the direct effect of the nonavalent vaccine with the cross-protection of bivalent and quadrivalent vaccines results in the reduction of HPV 6/11/16/18/31/33/45/52/58. HPV vaccination has been shown to provide herd protection as well. Two-dose HPV vaccine schedules showed no difference in seroconversion from three-dose schedules. However, the use of a single-dose HPV vaccination schedule remains controversial. For males, the quadrivalent HPV vaccine possibly reduces the incidence of external genital lesions and persistent infection with HPV 6/11/16/18. Evidence regarding the efficacy and risk of HPV vaccination and HIV infection remains limited. HPV vaccination has been shown to be highly effective against oral HPV type 16/18 infection, with a significant percentage of participants developing IgG antibodies in the oral fluid post vaccination. However, the vaccines’ effectiveness in reducing the incidence of and mortality rates from HPV-related head and neck cancers should be observed in the long term. In anal infections and anal intraepithelial neoplasia, the vaccines demonstrate high efficacy. While HPV vaccines are very effective, screening for related cancers, as per guidelines, is still recommended.

Micro Electrical Discharge Machining Thermal Effect on Micro-Cracks Generation on Silicon Material

Various novel 3D micro machining technologies were researched and developed for silicon micro mechanical system fabrication. Micro EDM is one of them. The material removal mechanism is thermal sparking erosion and is completely independent with regards to the crystalline orientation of silicon, therefore there is no orientation constraint in processing the complex 3D geometry of silicon wafers. As thermal sparking implied, the process features local area high temperature melting and evaporating, and this characteristic has an adverse side-effect on the sparked surface integrity. One important concern is the generation of micro cracks, which would provide an adverse effect on the fatigue life of the micro feature element made of silicon. For this consideration, in this paper, with the experiment and SEM picture analysis approach, the author explored the micro crack generation characteristics on mono crystalline silicon wafers under micro EDM with available sparking energies and on the different crystal orientation surface machining. The generation of micro cracking is not only related with the sparking energy but also related with the crystalline orientation. The {100} orientation is the strongest surface to resist crack generation. For a strong-doped P type silicon wafer, there exists a maximum crack energy threshold. If single sparking energy is over this threshold, micro cracks unavoidably would be generated on any orientation surface. Two types of chemical etching post processes that can remove cracks on sparked surfaces are also tested and discussed.

Memantine Protects against Paclitaxel-Induced Cognitive Impairment through Modulation of Neurogenesis and Inflammation in Mice

Chemotherapy-induced cognitive impairment (CICI) is an adverse side effect of cancer treatment with increasing awareness. Hippocampal damage and related neurocognitive impairment may mediate the development of CICI, in which altered neurogenesis may play a role. In addition, increased inflammation may be related to chemotherapy-induced hippocampal damage. Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that may enhance neurogenesis and modulate inflammation, may be useful for treating CICI. To test this hypothesis, paclitaxel was administered to eight-week-old male B6 mice to demonstrate the relationship between CICI and impaired neurogenesis, and then, we evaluated the impact of different memantine regimens on neurogenesis and inflammation in this CICI model. The results demonstrated that both the pretreatment and cotreatment regimens with memantine successfully reversed impaired neurogenesis and spatial memory impairment in behavior tests. The pretreatment regimen unsuccessfully inhibited the expression of peripheral and central TNF- and IL-1 and did not improve the mood alterations following paclitaxel treatment. However, the cotreatment regimen led to a better modulatory effect on inflammation and restoration of mood disturbance. In conclusion, this study illustrated that impaired neurogenesis is one of the mechanisms of paclitaxel-induced CICI. Memantine may serve as a potential treatment for paclitaxel-induced CICI, but different treatment strategies may lead to variations in the treatment efficacy.

Tissue Damage in Radiation-Induced Oral Mucositis Is Mitigated by IL-17 Receptor Signaling

Oral mucositis (OM) is a treatment-limiting adverse side effect of radiation and chemotherapy. Approximately 80% of patients undergoing radiotherapy (RT) for head and neck cancers (HNC) develop OM, representing a major unmet medical condition. Our understanding of the immunopathogenesis of OM is limited, due in part to the surprising paucity of information regarding healing mechanisms in the oral mucosa. RNAseq of oral tissue in a murine model that closely mimics human OM, showed elevated expression of IL-17 and related immune pathways in response to head and neck irradiation (HNI). Strikingly, mice lacking the IL-17 receptor (IL-17RA) exhibited markedly more severe OM. Restoration of the oral mucosa was compromised in Il17ra−/− mice and components associated with healing, including matrix metalloproteinase 3, 10 and IL-24 were diminished. IL-17 is typically associated with recruitment of neutrophils to mucosal sites following oral infections. Unexpectedly, in OM the absence of IL-17RA resulted in excessive neutrophil recruitment and immunopathology. Instead, neutrophil activation was IL-1R-driven in Il17ra−/− mice. Blockade of IL-1R and depletion of neutrophils lessened the severity of damage in these mice. Overall, we show IL-17 is protective in OM through multiple mechanisms including restoration of the damaged epithelia and control of the neutrophil response. We also present a clinically relevant murine model of human OM to improve mechanistic understanding and develop rational translational therapeutics.

Essential Oils from the Leaves of Ocimum Basilicum L., Persicaria Odorata and Coriandrum Sativum L. In Malaysia: Antiurolithic Activity Study Based On Calcium Oxalate Crystallisation

Calcium oxalate is one of the most common components in urolithiasis. Its treatment includes the use of synthetic drugs, ultrasound and surgery. However, cheaper alternative treatment using herbal medicine with less adverse side effect is preferred. Essential oils from Thai basil (Ocimum bacilicum L.), Vietnamese coriander (Persicaria odorata) and Chinese parsley (Coriandum sativum L.) were extracted and investigated for antiurolithic activity based on calcium oxalate crystallisation. Most of the crystals formed in control sample were hexagonal calcium oxalate monohydrate with sizes ranging between 3 to 4 m. The size of the crystals was found to be slightly reduced in O. bacilicum oil (2-4 m) at high concentration with less aggregation of crystals. Samples with P. odorata oil gave smaller crystal size (3 m) mainly in dehydrate form and the oil was also found to inhibit the aggregation of the crystals at high concentration. C. sativum oil enhanced crystallisation (5-6 m) with increased concentration and showed high aggregation of the crystals. This preliminary study shows the therapeutic potential of these medicinal plants to be used in traditional anti-urolithic therapy.

Differences in the quasi-biennial oscillation response to stratospheric aerosol modification depending on injection strategy and species

A known adverse side effect of stratospheric aerosol modification (SAM) is the alteration of the quasi-biennial oscillation (QBO), which is caused by the stratospheric heating associated with an artificial aerosol layer. Multiple studies found the QBO to slow down or even completely vanish for point-like injections of SO2 at the Equator. The cause for this was found to be a modification of the thermal wind balance and a stronger tropical upwelling. For other injection strategies, different responses of the QBO have been observed. A theory which is able to explain those differences in a comprehensive manner has not yet been presented. This is further complicated by the fact that the simulated QBO response is highly sensitive to the used model even under identical boundary conditions. Therefore, within this study we investigate the response of the QBO to SAM for three different injection strategies (point-like injection at the Equator, point-like injection at 30∘ N and 30∘ S simultaneously, and areal injection into a 60∘ wide belt along the Equator). Our simulations confirm that the QBO response significantly depends on the injection location. Based on the thermal wind balance, we demonstrate that this dependency is explained by differences in the meridional structure of the aerosol-induced stratospheric warming, i.e., the location and meridional extension of the maximum warming. Additionally, we also tested two different injection species (SO2 and H2SO4). The QBO response is qualitatively similar for both investigated injection species. Comparing the results to corresponding results of a second model, we further demonstrate the generality of our theory as well as the importance of an interactive treatment of stratospheric ozone for the simulated QBO response.

Oxaliplatin-related interstitial pneumonia with high-grade fever and relative bradycardia as the presenting signs: a case report

Background Although drug-induced interstitial pneumonia is a well-known adverse side-effect of cancer chemotherapy, the disease is difficult to detect in the early phase. We report a case of oxaliplatin-induced interstitial pneumonia in which eosinophilia and high-grade fever with relative bradycardia were useful presenting signs for the early diagnosis. Case presentation A 76-year-old Japanese woman with postoperative recurrent rectal cancer (peritoneal dissemination and liver metastasis) was admitted to our hospital because of productive cough and consolidation on thoracic computed tomography (CT) images. Two months prior to the consultation, she had started chemotherapy (fluorouracil, oxaliplatin, and bevacizumab). After finishing three courses of chemotherapy, she developed fever and was noted to have relative bradycardia. After another two courses of chemotherapy, she developed productive cough, chest discomfort, and high-grade fever. At this time, thoracic CT revealed patchy areas of consolidation distributed predominantly in the periphery. Despite the administration of tazobacterium/piperacillin, the consolidation seen on CT scans gradually worsened. Fiberoptic bronchoscopy was performed, and bronchoalveolar lavage fluid analysis showed increased lymphocytes, eosinophils, and total cell count but a low CD4/ CD8 ratio. No specific pathogen was identified. With a diagnosis of interstitial pneumonia, prednisolone was started and chemotherapy was temporarily discontinued. Her productive cough gradually decreased, and the infiltrative shadows on the thoracic CT scans improved. Conclusion Although cases of oxaliplatin-related pneumonia with complicating relative bradycardia are not uncommon, drug-induced interstitial pneumonia should be taken into account in the differential diagnosis. In this case, an increased circulating eosinophil count and high-grade fever with relative bradycardia were the first signs of drug-induced interstitial pneumonia.

LDH-doped electrospun short fibers enable dual drug loading and multistage release for chemotherapy of drug-resistant cancer cells

Conventional cancer chemotherapy is facing difficulties in improving the bioavailability, overcoming the severe adverse side effect of chemotherapeutics and reversing the multidrug resistance of cancer cells. To address these challenges,...