Zinc finger protein 263 upregulates interleukin 33 and suppresses autophagy to accelerate the malignant progression of non-small cell lung cancer / La proteína 263 con dedos de zinc regula positivamente la interleucina 33 y suprime la autofagia para acelerar la progresión maligna del cáncer de pulmón de células no pequeñas

Purpose: Non-small cell lung cancer (NSCLC) is a complex disease that remains a major public health concern worldwide. One promising avenue for NSCLC treatment is the targeting of transcription factors that regulate key pathways involved in cancer progression. In this study, we investigated the role of the transcription factor ZNF263 in NSCLC and its impact on the regulation of IL33, apoptosis, and autophagy. Methods: Levels of ZNF263 in tissues and cell lines were identified, after which the effects of its knockdown on cellular malignant behaviors, apoptosis and autophagy were assessed. Based on bioinformatics analysis, ZNF263 was found to bind to IL33 promoter, their mutual relationship was confirmed, as well as the role of IL33 in the regulation of ZNF263. The involvement of ZNF263 in the growth of xenograft tumors was assessed using tumor-bearing nude mouse models. Results: Experimental results revealed that ZNF263 was upregulated in NSCLC tissue samples and cell lines. Its expression level is positively correlated with cellular malignant behaviors. We further demonstrated that ZNF263 upregulated IL33 expression, which, in turn, promoted the proliferation and migration, inhibited apoptosis and autophagy in NSCLC cells. Furthermore, ZNF263 knockdown reduced the growth of xenograft tumors in nude mice. Conclusion: This finding suggests that the inhibition of ZNF263 or IL33 may represent a novel therapeutic strategy for NSCLC. Importantly, our results highlight the crucial role of transcription factors in NSCLC and their potential as therapeutic targets.(AU)

Assessment of the feed additive consisting of Pediococcus pentosaceus DSM 14021 for all animal species for the renewal of its authorisation (Chr. Hansen A/S).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Pediococcus pentosaceus DSM 14021, a technological additive for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The Panel concluded that the additive remains safe for all animal species, consumers and the environment under the authorised conditions of use. Regarding user safety, the Panel considers that any exposure through skin and respiratory tract is considered a risk. The Panel cannot conclude on the eye irritation potential of the additive due to the lack of data. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Fungal-Bacterial Mutualism: Species and Strain-Dependent Simultaneous Modulation of Branched-Chain Esters and Indole Derivatives in Fermented Sausages through Metabolite Cross-Feeding.

The precise impact of species and strain diversity on fungal-bacterial interactions and the overall community functioning has remained unclear. First, our study revealed how Debaryomyces hansenii influences diverse bacteria to accumulate key metabolites in a simulated fermented food system. For flavor, D. hansenii promoted the accumulation of branched-chain esters in Staphylococcus xylosus by promoting growth and facilitating the precursor branched-chain acids transformations but hindered the accumulation of Staphylococcus equorum. Furthermore, fungal-bacterial interactions displayed diversity among S. equorum strains. For bioactive compounds, species and strain diversity of lactic acid bacteria (LAB) also influences the production of indole derivatives. Then, we investigated specific metabolic exchanges under reciprocal interaction. Amino acids, rather than vitamins, were identified as the primary drivers of the bacterial growth promotion. Moreover, precursor transformations by D. hansenii played a significant role in branched-chain esters production. Finally, a synthetic community capable of producing high concentrations of branched-chain esters and indole derivatives was successfully constructed. These results provide valuable insights into understanding and designing synthetic communities for fermented sausages.

[Correction to the Article "Hansen's Disease: An Unusual Manifestation of an Ancient Disease", Published on Acta Med Port 2024 Mar;37(3):215-219]. / Errata ao Artigo "Doença de Hansen: Apresentação Incomum de uma Doença Antiga", Publicado em Acta Med Port 2024 Mar;37(3):215-219.

On page 215, list of authors, where it reads (in red): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1 It should read (in bold): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1, Rita BOUCEIRO MENDES3, Pedro VASCONCELOS3 On the same page 215, footer (authors affiliation), where it reads (in red): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. It should read (in bold): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. 3. Serviço de Dermatologia. Hospital de Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisboa. Portugal. Article published with errors: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20599.

Na página 215, na linha de autoria onde se lê, (a vermelho): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1 Deverá ler-se (a negrito): Mário FERREIRA1, Carlos GRIJÓ2, Joana PAULO1, Marta FONSECA1, Zélia NEVES1, Rita BOUCEIRO MENDES3, Pedro VASCONCELOS3 Na mesma página 215, em rodapé (afiliação dos autores), onde se lê (a vermelho): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. Deverá ler-se (a negrito): 1. Medicina III. Hospital Fernando Fonseca. Amadora. Portugal. 2. Serviço de Medicina Interna. Centro Hospitalar Universitário de São João. Porto. Portugal. 3. Serviço de Dermatologia. Hospital de Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisboa. Portugal. Artigo publicado com erros: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/20599.

Mitigating postharvest quantitative and qualitative losses in mango fruits through the application of biocontrol agents: An in-vivo and in-vitro assessment.

Mango is a commercial fruit crop of India that suffers huge postharvest losses every year. The application of biocontrol agents (BCAs) bears a vast potential for managing the same, which is yet to be exploited to its fullest extent. Hence, studies were conducted for BCAs application of Debaryomyces hansenii, Bacillus subtilis and Pseudomonas fluorescens strains on mango fruit under in-vitro, in-vivo conditions to know the efficacy of these BCAs on the postharvest pathogen, shelf life and quality retention of mango fruit. The 'poisoned food technique' was attempted for in-vitro studies. For the in-vivo studies, fruit of the commercial cultivar 'Amrapali' were un-inoculated and pre-inoculated with major postharvest pathogens (anthracnose: Colletotrichum gloeosporioides and stem-end rot: Botryodiplodia theobromae) were treated with BCA, followed by ambient storage at (24 ± 4 °C, 75 ± 5 % RH). From the results, it has been observed that under in vitro studies, BCA Debaryomyces hansenii (Strain: KP006) and Bacillus subtilis (Strain: BJ0011) at the treatment level 108 CFU mL-1 while, the Pseudomonas fluorescens at 109 CFU mL-1 (Strain: BE0001) were significantly effective for pathogen inhibition. However, under the in vivo studies, the BCA Debaryomyces hansenii (Strain: KP006) at 108 CFU mL-1 treatment level was found to significantly reduce the pathogen's decay incidence while positively influencing the shelf life and biochemical (quality) attributes. This treatment increased the storage life of mango fruit by more than three days over control fruit. Therefore, BCA Debaryomyces hansenii (Strain: KP006) at 108 CFU mL-1 can be used to control the postharvest pathological loss of mango fruit without affecting its internal quality.

Localised erythema nodosum leprosum-A rare entity managed with thalidomide.

Leprosy is caused by Mycobacterium leprae. The condition primarily affects the skin and peripheral nerves. There are two types of leprosy reactions, Type 1 and Type 2 or erythema nodosum leprosum (ENL). ENL is a severe multi-system, immune-mediated complication of lepromatous leprosy. It is characterised by widespread painful cutaneous nodules, fever and peripheral oedema. This report discusses the unusual case of a 29-year-old woman who developed a localised form of ENL which required thalidomide to induce remission.

Should prophylaxis against Pneumocystis jirovecii pneumonia be considered in selected patients with leprosy reactions?

Leprosy reactions often require prolonged high-dose steroids or immunosuppressive drugs, putting patients at risk of Pneumocystis jirovecii pneumonia (PJP). However, no PJP cases are reported, possibly due to dapsone treatment for leprosy. In patients with leprosy reactions not receiving dapsone because of toxicity or resistance and requiring long-term immunosuppression, PJP prophylaxis should be considered.

Spatial-temporal trends in leprosy burden and its associations with socioeconomic and physical geographic factors: results from the Global Burden of Disease Study 2019.

OBJECTIVES: The purpose of our study was to assess the multiscalar changes in leprosy burden and its associated risk factors over the last three decades. STUDY DESIGN: We conducted an in-depth examination of leprosy's spatial-temporal trends at multiple geographical scale (global, regional, and national), utilizing information from Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2019). METHODS: Incidence and the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) of leprosy were determined, with countries categorized based on leprosy incidence changes. We examined socioeconomic and physical geography influences on leprosy incidence via Spearman correlation analysis, using ternary phase diagrams to reveal the synergetic effects on leprosy occurrence. RESULTS: Globally, incident cases of leprosy decreased by 27.86% from 1990 to 2019, with a reduction in ASIR (EAPC = -2.53), yet trends were not homogeneous across regions. ASIR and EAPC correlated positively with sociodemographic index (SDI), and an ASIR growth appeared in high SDI region (EAPC = 3.07). Leprosy burden was chiefly distributed in Tropical Latin America, Oceania, Central Sub-Saharan Africa, and South Asia. Negative correlations were detected between the incidence of leprosy and factors of SDI, GDP per capita, urban population to total population, and precipitation, whereas the number of refugee population, temperature, and elevation showed opposite positive results. CONCLUSIONS: Despite a global decline in leprosy over the past three decades, the disparities of disease occurrence at regional and national scales still persisted. Socioeconomic and physical geographic factors posed an obvious influence on the transmission risk of leprosy. The persistence and regional fluctuations of leprosy incidence necessitate the ongoing dynamic and multilayered control strategies worldwide in combating this ancient disease.

A comparative study on the detection of Mycobacterium leprae DNA in urine samples of leprosy patients using Rlep-PCR with other conventional samples.

BACKGROUND: Mycobacterium leprae causes leprosy that is highly stigmatized and chronic infectious skin disease. Only some diagnostic tools are being used for the identification M. leprae in clinical samples, such as bacillary detection, and histopathological tests. These methods are invasive and often have low sensitivity. Currently, the PCR technique has been used as an effective tool fordetecting M. leprae DNA across different clinical samples. The current study aims to detect M. leprae DNA in urine samples of untreated and treated leprosy patients using the Rlep gene (129 bp) and compared the detection among Ridley-Jopling Classification. METHODS: Clinical samples (Blood, Urine, and Slit Skin Smears (SSS)) were collected from leprosy and Non-leprosy patients. DNA extraction was performed using standard laboratory protocol and Conventional PCR was carried out for all samples using Rlep gene target and the amplicons of urine samples were sequenced by Sanger sequencing to confirm the Rlep gene target. RESULTS: The M. leprae DNA was successfully detected in all clinical samples across all types of leprosy among all the study groups using RLEP-PCR. Rlep gene target was able to detect the presence of M. leprae DNA in 79.17% of urine, 58.33% of blood, and 50% of SSS samples of untreated Smear-Negative leprosy patients. The statistical significant difference (p = 0.004) was observed between BI Negative (Slit Skin Smear test) and RLEP PCR positivity in urine samples of untreated leprosy group. CONCLUSION: The PCR positivity using Rlep gene target (129 bp) was highest in all clinical samples among the study groups, across all types of leprosy. Untreated tuberculoid and PNL leprosy patients showed the highest PCR positivity in urine samples, indicating its potential as a non-invasive diagnostic tool for leprosy and even for contact screening.

Audiological Evaluation of Leprosy Patients in an Endemic Area of Central India: A Case-Control Pilot Study.

There are discrepancies in the literature about the specific influence of leprosy on auditory functions. In routine clinical practice regular hearing screening of leprosy patients is not done. Due to conflicting reports of auditory system involvement in the literature, we conducted this case control study to evaluate the need of regular hearing screening in leprosy patients. A complete otological examination of thirty leprosy patients was conducted. Thirty age and sex matched healthy individual attending ear, nose and throat outpatient department were enrolled as control. Ten cases (33.3%) out of the thirty leprosy patients were found to have high frequency (4 and 8 kHZ) sensorineural hearing loss. The results of this study suggest that leprosy patients require routine monitoring for auditory functions for early identifications of sensorineural hearing loss. As our study is a case-control study with small sample size, in future large prospective studies are required to evaluate the correlation of hearing loss with leprosy and to see the progression hearing loss. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04381-1.

A novel method of assessing intraoperative surgical margins in patients with dermatofibrosarcoma protuberans: A specimen radiography system.

Background Dermatofibrosarcoma protuberans (DFSP) is one of the most challenging cutaneous cancers in surgical clinic practice. Excision with negative margins is essential for effective disease control. However, wide surgical margins and maximal tissue conservation are mutually exclusive. Mohs micrographic surgery conserves tissue but is time-consuming. Thus, we developed a novel specimen radiography system that can be used intraoperatively. Aims To introduce a specimen radiography system for evaluating intraoperative surgical margins in patients with dermatofibrosarcoma protuberans. Methods Since September 2017, we have treated seven biopsy-proven cases of local DFSPs via local excision with surgical margins of 2-4 cm. During operations, the operative specimens were screened using the specimen radiography system. All surgical specimens were pathologically examined intraoperatively. Results Five patients were men and two were women, of median age 36 years. The mean radiographic screening time was 9.7 ± 2.3 min. Radiographically negative margins were confirmed intraoperatively. The minimal margin width ranged from 5.0 to 35.4 mm (mean width 16.9 ± 10.4 mm). The intraoperatively negative radiographic margins were consistent with those revealed by postoperative pathology. The minimal pathological margin width ranged from 4.0 to 34.5 mm (mean 16.6 ± 10.1 mm) and was not significantly different from the intraoperative data. Limitations The sample size was small and positive or negative predictive values were not calculated. Conclusions We introduce a novel method of intraoperative surgical margin assessment for DFSP patients. It may find broad clinical and research applications during oncoplastic surgery.