Immunotherapeutic targets in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5-year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in-depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signalling pathways. In this review, we discuss immunotherapeutic targets in NSCLC tumours and how the TME may influence patients' response to immunotherapy.     

Hand-arm vibration syndrome and its prevalence in the present status of private forestry enterprises in Japan

Summary Currently there are no limitations on age of employment on private forestries in Japan. Hence, it was hypothesized that in these kind of enterprises, elderly chain saw operators, or those with long-term exposure, might be at higher risk of developing hand-arm vibration syndrome (HAVS). We consequently investigated the prevalence of HAVS in 447 chain saw workers on private forestries in Gifu Prefecture, Japan, with particular reference to age and exposure period. Of this population, 43 (9.6%) had signs and symptoms of vibration-induced white finger (VWF), and among these workers the severity of finger blanching was significantly correlated (P < 0.01) with the exposure period. Classification of all subjects by exposure period showed that workers with 30 years' exposure had higher prevalences of VWF (20.9%) and numbness of the hands (25.4%) compared to other groups. Significant differences (P < 0.01) were found between the functional capacities of workers with VWF and those of control subjects. We concluded that (a) the elderly chain saw operators and those with longer exposure should be moved to other jobs with a lower or no risk of exposure to vibration, and (b) the results of screening tests, even without cold water immersion (which we did not employ, in order to protect workers' hands), could be helpful for the identification of workers with VWF.     

Combined effects of caffeine and malnutrition on the newborn rat's myocardium.

We hypothesized that the pathological effects on the neonatal rat heart could be aggravated by Cu deficiency due to the combined effects of caffeine exposure and malnutrition. Upon birth, pups were mixed and randomly picked; 8 pups were assigned to each dam and then divided into 4 groups. Group 1 dams received a normal diet containing 20% protein. Group 2 dams were fed 20% protein diet supplemented with caffeine (4 mg/100 g BW). Group 3 dams received 6% protein diet as a malnourished group, and group 4 dams received 6% protein diet supplemented with caffeine (4 mg/100 g BW). On postnatal day 10, dams and pups were killed. Group 2 tended to have a decrease in the Cu levels of dams' plasma and milk and in pups' plasma and heart tissue compared to those of group 1. This pattern was not observed consistently between groups 3 and 4. Transmission electron microscopy of group 2 pups' hearts revealed a degree of disruption in the mitochondria compared to normal mitochondria seen in group 1. There was no consistent change in the mitochondria of group 4 compared to group 3. The caffeine level observed in all categories of group 4 (dams' plasma and milk, pups' plasma and heart tissue) was lower than those in group 2. Although malnutrition affected body weight and heart weight, combined effects of caffeine and malnutrition on Cu content in the neonatal heart was relatively minor compared to the well nourished group. This well nourished group showed that the effects of caffeine on Cu were more consistent, resulting the changes of mitochondria.     

Spontaneous xenogeneic GvHD in Wilms' tumor Patient‐Derived xenograft models and potential solutions

Severely immunocompromised NOD.Cg‐Prkdc ^scid Il2rg ^tm1Sug (NOG) mice are among the ideal animal recipients for generation of human cancer models. Transplantation of human solid tumors having abundant tumor‐infiltrating lymphocytes (TILs) can induce xenogeneic graft‐versus‐host disease (xGvHD) following engraftment and expansion of the TILs inside the animal body. Wilms'' tumor (WT) has not been recognized as a lymphocyte‐predominant tumor. However, 3 consecutive generations of NOG mice bearing WT patient‐derived xenografts (PDX) xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention. In the initial generation, dermatitis, auto‐amputation of digits, weight loss, lymphadenopathy, hepatitis, and interstitial pneumonitis were observed. Despite antibiotic treatment, no response was noticed, and thus the animals were prematurely euthanized (day 47 posttransplantation). Laboratory and histopathologic evaluations revealed lymphoid infiltrates positively immunostained with anti‐human CD3 and CD8 antibodies in the xenografts and primary tumor, whereas no microbial infection or lymphoproliferative disorder was found. Mice of the next generation that lived longer (91 days) developed sclerotic skin changes and more severe pneumonitis. Cutaneous symptoms were milder in the last generation. The xenografts of the last 2 generations also contained TILs, and lacked lymphoproliferative transformation. The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD. While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts, this report for the first time documented serial xGvHD in consecutive passages of WT PDX‐bearing models and discussed potential solutions to prevent such an undesired complication.     

Assessing Consumer Willingness to Pay for Nutritional Information Using a Dietary App

A healthy society is the foundation of development in every country, and one way to achieve a healthy society is to promote healthy nutrition. An unbalanced diet is one of the leading causes of noncommunicable diseases globally. If food was correctly selected and correctly consumed, both the problems of overeating and lack of nutrition could be largely solved while also decreasing public health costs. Interventions such as presenting necessary information and warning labels would help consumers make better food choices. Hence, providing nutritional information to consumers becomes essential. The present study investigates the importance of nutrition information labels on consumers’ preferences by estimating their willingness to pay for features and information provided by a dietary software program (app). An application can easily display the information to the consumers and help them make informed food choices. A discrete choice experiment investigated consumers’ preferences and willingness to pay to receive nutritional information. Mixed multinomial logit and latent class analysis were applied. The results showed the existence of heterogeneity in consumer preferences for different nutritional information provided by the application. Consumers are willing to pay more for salt and fat alerts. The results of this study allow for the analysis of consumers’ interest in nutritional information. Such results are essential for the industry for future investments in similar applications that potentially could help consumers make better informed choices.     

Social Contact Patterns Associated With Tuberculosis: A Case-control Study in Southwest Iran

ObjectivesTuberculosis (TB) is a major public health concern worldwide. Social contact patterns can affect the epidemiology and risk of airborne diseases such as TB. This study was designed to investigate the social contact patterns associated with TB.MethodsIn this case-control study, groups of participants with and without TB were matched by age and sex. Participants reported the nature, location, frequency, and average duration of social contacts over 1 month. The duration and number of social and spatial contacts were compared between groups using the chi-square test and the t-test. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantify the relationship between social contact time and TB status. Data were analyzed using Stata version 11 statistical software. A p-value of <0.05 was considered to indicate statistical significance.ResultsIn this study, 80 patients with TB and 172 control participants were included, and a total of 3545 social contacts were registered. Social contact with family members (OR, 1.72; 95% CI, 1.10 to 2.40), contact with a person with TB (OR, 1.53; 95% CI, 1.16 to 2.01), and contact at the participant’s home (OR, 1.42; 95% CI, 1.19 to 1.82) were significantly associated with TB status.ConclusionsThe duration of long-term social contact, rather than the number of contacts, may be the main contact-related factor associated with TB transmission in this population. The focus of contact-tracing efforts should be on finding and treating both family members and long-term contacts in non-household settings.     

Retraction: Design of 1-methylimidazolium tricyanomethanide as the first nanostructured molten salt and its catalytic application in the condensation reaction of various aromatic aldehydes,amides and β-naphthol compared with tin dioxide nanoparticles

Retraction of ‘Design of 1-methylimidazolium tricyanomethanide as the first nanostructured molten salt and its catalytic application in the condensation reaction of various aromatic aldehydes, amides and β-naphthol compared with tin dioxide nanoparticles’ by Mohammad Ali Zolfigol et al., RSC Adv., 2015, 5, 45027–45037, https://doi.org/10.1039/C5RA02718G.

The Royal Society of Chemistry hereby wholly retracts this RSC Advances article as the synthesis of 1-methylimidazolium tricyanomethanide reported in the article, whereby tricyanomethane is used as a starting material, is not reproducible. The authors stated that they did not report the synthesis of tricyanomethane in the published paper as they purchased this compound from a commercial center and used it in the synthesis of ionic liquids, molten salts and various kinds of catalysts. The authors thought the reaction between tricyanomethane and organic bases is a simple acid–base reaction, therefore they did not cite the previously reported literature and its related history for the preparation of tricyanomethane. However, according to papers by Banert et al.,^1,2 and based on their obtained analysis of the chemical sold to them as tricyanomethane, it became clear to the authors that this purchased compound was not tricyanomethane as there were differences in the ¹H NMR and ¹³C NMR chemical shift between the purchased compound and the reports of Banert et al.¹ According to these documents, the authors believe that the compound sold to them as tricyanomethane was fake. While the authors have now re-prepared 1-methylimadazolium tricyanomethanide, by synthesising potassium tricyanomethanide as a starting material for the synthesis,^3–5 the synthesis reported in this article is not accurate. Therefore, this article is being retracted to avoid misleading readers and to protect the accuracy and integrity of the scientific record.Mohammad Ali Zolfigol, Saeed Baghery and Ahmad Reza Moosavi-Zare oppose the retraction. Seyed Mohammad Vahdat, Heshmatollah Alinezhad and Mohammad Norouzi were contacted but did not respond.Signed: Laura Fisher, Executive Editor, RSC AdvancesDate: 17^th August 2022     

On the Morphological Deviation in Additive Manufacturing of Porous Ti6Al4V Scaffold: A Design Consideration

Additively manufactured Ti scaffolds have been used for bone replacement and orthopaedic applications. In these applications, both morphological and mechanical properties are important for their in vivo performance. Additively manufactured Ti6Al4V triply periodic minimal surface (TPMS) scaffolds with diamond and gyroid structures are known to have high stiffness and high osseointegration properties, respectively. However, morphological deviations between the as-designed and as-built types of these scaffolds have not been studied before. In this study, the morphological and mechanical properties of diamond and gyroid scaffolds at macro and microscales were examined. The results demonstrated that the mean printed strut thickness was greater than the designed target value. For diamond scaffolds, the deviation increased from 7.5 μm (2.5% excess) for vertical struts to 105.4 μm (35.1% excess) for horizontal struts. For the gyroid design, the corresponding deviations were larger, ranging from 12.6 μm (4.2% excess) to 198.6 μm (66.2% excess). The mean printed pore size was less than the designed target value. For diamonds, the deviation of the mean pore size from the designed value increased from 33.1 μm (−3.0% excess) for vertical struts to 92.8 μm (−8.4% excess) for horizontal struts. The corresponding deviation for gyroids was larger, ranging from 23.8 μm (−3.0% excess) to 168.7 μm (−21.1% excess). Compressive Young’s modulus of the bulk sample, gyroid and diamond scaffolds was calculated to be 35.8 GPa, 6.81 GPa and 7.59 GPa, respectively, via the global compression method. The corresponding yield strength of the samples was measured to be 1012, 108 and 134 MPa. Average microhardness and Young’s modulus from α and β phases of Ti6Al4V from scaffold struts were calculated to be 4.1 GPa and 131 GPa, respectively. The extracted morphology and mechanical properties in this study could help understand the deviation between the as-design and as-built matrices, which could help develop a design compensation strategy before the fabrication of the scaffolds.     

Anti-inflammatory and analgesic properties of Heracleum persicum essential oil and hydroalcoholic extract in animal models

Ethnopharmacological relevance

Fruits of Heracleum persicum (Apiaceae) are used as pain killer in Iranian folkloric medicine.

Aims of study

To evaluate the anti-inflammatory and analgesic effects of the hydroalcoholic extract and essential oil of the plant fruits and analyzing the essential oil.

Materials and methods

Essential oil and hydroalcoholic extracts of the fruits were prepared according to standard methods and the components of essential oil were identified using GC–MS method. The acetic acid-induced writhing response and formalin test were used in male mice to assess analgesic activity. For evaluation of anti-inflammatory effect, carrageenan-induced rat paw edema was used.

Results

Hexyl butyrate (56.5%), octyl acetate (16.5%), hexyl 2-methylbutanoate (5.2%) and hexyl isobutyrate (3.4%) were identified as the major constituents of the oil. Oral or intraperitoneal administration of Heracleum persicum essential oil (HPEO) at doses of 50–200 mg/kg and Heracleum persicum hydroalcoholic extract (HPHE) at doses of 250 and 500 mg/kg significantly reduced acetic acid-induced abdominal constrictions. HPEO and HPHE also significantly attenuated the pain response of the second phase of formalin test.In carrageenan test HPEO at doses of 100 and 200 mg/kg and HPHE at a dose of 400 mg/kg induced a significant reduction of paw edema.

Conclusions

These results clearly show the analgesic and anti-inflammatory effects of the plant essential oil and hydroalcoholic extract. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.