Infantile orbital abscess: clinical presentation, microbiological profile, and management outcomes.

PURPOSE: Orbital abscesses in children are not uncommon. Unless managed in a timely fashion, they can potentially lead to vision-threatening as well as life-threatening complications. The objective of this study is to report the clinical and microbiological profile and management outcomes in infants presenting with orbital abscesses. MATERIALS AND METHODS: A retrospective review of electronic medical records of children younger than 1 year with a diagnosis of an orbital abscess was done. The data was collected from a time period of 12 years (2007-2019). The data collected included mode of presentation, radiological, microbiological and histopathological features, and the final outcome. RESULTS: A total of nine patients met the inclusion criteria. The mean age at presentation was 19 weeks. Three patients had upper respiratory tract infection, one had a congenital nasolacrimal duct obstruction, two had sinusitis, and one patient had neonatal sepsis. All patients underwent imaging following which abscess drainage was performed. Methicillin-sensitive Staphylococcus aureus was the most common organism, which was isolated in five patients, Methicillin-resistant S. aureus was isolated in three, while one patient had Entomophthorales fungal infection. The median follow-up period was 10 months (range 5 days to 89 months). There was no recurrence in the cohort. At least one patient had visual impairment at the last follow up. CONCLUSION: Orbital abscesses in infants are rare. Imaging and prompt drainage of the abscess supplemented by appropriate antimicrobial regimen leads to a successful outcome.

A rare case of congenital piloleiomyoma of the eyelid.

Cutaneous leiomyoma is an infrequently occurring benign smooth muscle neoplasm of skin. Piloleiomyoma, angioleiomyoma, and genital leiomyoma are the three forms of the cutaneous leiomyoma. Piloleiomyoma arises from arrector pili muscle and is commonly seen in the adult population. Congenital piloleiomyoma is extremely rare and has never been reported to arise from the eyelid. We report a case of a neonate presenting with upper eyelid mass lesion since birth causing mechanical ptosis. Incisional biopsy followed by histopathology and immunohistochemistry established the diagnosis of piloleiomyoma. There was associated cryptorchidism in our case, a systemic association that has never been reported. Considering the benign nature of the lesion the child was kept under regular follow up without attempting any further removal.

Inhibition of JNK-Mediated Autophagy Promotes Proscillaridin A- Induced Apoptosis via ROS Generation, Intracellular Ca+2 Oscillation and Inhibiting STAT3 Signaling in Breast Cancer Cells.

Breast cancer is the most heterogenous cancer type among women across the world. Despite concerted efforts, breast cancer management is still unsatisfactory. Interplay between apoptosis and autophagy is an imperative factor in categorizing therapeutics for cancer treatment. Proscillaridin A (PSD-A), a well-known cardiac glycoside used for cardiac arrest and arrythmias, has been unveiled in many cancer types but the underlying mechanism for apoptosis and autophagy in breast cancer is not fully understood. In our study, PSD-A restricted cell growth, inhibited STAT3 activation and induced apoptosis and autophagy in breast cancer cells via ROS generation and Ca+2 oscillation. Pretreatment of NAC and BAPTA-AM restored PSD-A induced cellular events in breast cancer cells. PSD-A induced apoptosis via DNA fragmentation, caspase-cascade activation, PARP cleavage, mitochondrial dysfunction, Bax/Bcl-2 proteins modulation and ER chaperone GRP78 inhibition along with decreased phosphorylation of ERK1/2. Inhibition of STAT3 activation was found to be associated with decreased phosphorylation of SRC. Moreover, PSD-A induced events of autophagy i.e. conversion of LC3-I to LC3-II, and Atg3 expression via JNK activation and decreased mTOR and AKT phosphorylation. In this study, pretreatment of SP600125, a JNK inhibitor, reduced autophagy and enhanced STAT3 inhibition and apoptosis. Additionally, SB203580, a commercial p38 inhibitor, stimulated STAT3 activation and improved autophagic events rate in breast cancer cells, displaying the role of the MAPK signaling pathway in interplay between apoptosis and autophagy. Our data suggest that the rate of apoptotic cell death is improved by blocking JNK-induced autophagy in PSD-A treated MCF-7 and MDA-MB-231 breast cancer cells.

Latcripin-7A, derivative of Lentinula edodes C91-3, reduces migration and induces apoptosis, autophagy, and cell cycle arrest at G1 phase in breast cancer cells.

Due to the high mortality rate and an increase in breast cancer incidence, it has been challenging for researchers to come across an effective chemotherapeutic strategy with minimum side effects. Therefore, the need for the development of effective chemotherapeutic drugs is still on the verge. Consequently, we approached a new mechanism to address this issue. The naturally available peptide named latcripin-7A (LP-7A), extracted from a mushroom called Lentinula edodes, provided us promising results in terms of growth arrest, apoptosis, and autophagy in breast cancer cells (MCF-7 and MDA-MB-231). Expressions of protein markers for apoptosis, autophagy, and cell cycle were confirmed via Western blot analysis. Migration and invasion assays were performed to analyze the anti-migratory and anti-invasive properties of LP-7A, while cell cycle analysis was performed via flow cytometry to evaluate its affect over cell growth. Supportive assays were performed like acridine orange, Hoechst 33258 stain, DNA fragmentation, and mitochondrial membrane potential (MMP) to further confirm the anticancer effect of LP-7A on breast cancer cell lines. It is concluded that LP-7A effectively reduces migration and promotes apoptosis as well as autophagy in MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell growth arrest at G0/G1 phase and decreasing mitochondrial membrane potential without adverse effects on MCF-10A normal breast cells. KEY POINTS: • In this study, we have investigated the anti-cancer activity of novel latcripin-7A (LP-7A), a protein extracted as a result of de novo characterization of Lentinula edodes C91-3. • We conclude in our research work that LP-7A can initiate diverse cell death-related events, i.e., apoptosis and autophagy in both triple-positive and triple-negative breast cancer cell lines by interacting with different nodes of cellular signaling that can further be investigated in vivo to gain a better understanding.

Assessment of bio-contaminants during COVID-19 outbreak from the indoor environment of Hail city, Kingdom of Saudi Arabia.

Biocontaminants are minute particles derived from different biological materials. Indoor biocontaminants are associated with major public health problems. In Gulf countries, it is more precarious due to the harsh climatic conditions, including high ambient temperatures and relative humidity. In addition, due to COVID-19 pandemic, most of the time public is inside their home. Therefore, the aim of the study was to determine the load of biocontaminants in the indoor environment of Hail city. The results showed that most of the bacteria are gram-positive and higher in polymicrobial (87.1%) than monomicrobial (62.7%) association. There was no significant association with sample collection time and types of isolates. The most abundant microbes found in all samples were Staphylococcus aureus followed by Bacillus spp. Among Gram-negative bacterial isolates, E. coli was most common in tested indoor air samples. The study will be useful to find the biocontaminants associated with risk factors and their impact on human health in indoor environment, especially during the COVID-19 pandemic. These results indicate the need to implement health care awareness programs in the region to improve indoor air quality.

Correction to: Taurine Ameliorates High Glucose Induced Apoptosis in HT-22 Cells.

Affiliations of authors Muhammad Shahbaz and Shahid Alam were incorrect in the published book. This has now been corrected as below.

Taurine Ameliorates High Glucose Induced Apoptosis in HT-22 Cells.

Diabetes causes memory loss. Hippocampus is responsible for memory and increased apoptosis was found in diabetes patients. Taurine improved memory in diabetes condition. However, mechanism is unclear. In current study, hippocampal cell line HT-22 cells were subjected to analysis as five groups i.e. Control, High glucose (HG) at concentration of 150 mM, HG + 10 mM (T1), 20 mM (T2) and 40 mM (T3) taurine solution. TUNEL assay showed that HG increased the number of apoptotic cell significantly while taurine reduced apoptosis. Taurine increased phosphorylation of Akt in HT-22 cell treated with HG, and increased phosphorylation of Bad (p-Bad) was seen suggesting involvement of Akt/Bad signaling pathway. Expression of Bcl-2 was reduced in HG group but taurine improved this. Bax expression showed opposite trend. This indicated that taurine may reduce apoptosis by controlling balance of Bcl-2 and Bax. When the activation of Akt was blocked by using of perifosine, the effect of taurine disappears either partially or altogether. Thus, it was clear that taurine reduces apoptosis via Akt/Bad pathway in HT-22 cells exposed to HG which further improves downstream balance of Bcl-2 and Bax. This mechanism may be involved in apoptosis of hippocampus cells in diabetic condition.

Up-regulated cathepsin C induces macrophage M1 polarization through FAK-triggered p38 MAPK/NF-κB pathway.

Increasing evidence indicates that in response to environmental changes, macrophages can dynamically change into two main functional phenotypes, namely M1 and M2. Depending on these different phenotypes, macrophages can produce either pro-inflammatory or anti-inflammatory factors which may affect the outcome of inflammation. Mastering the switching of M1/M2 phenotypes may provide therapeutic approaches to chronic inflammatory disease, such as atherosclerosis, rheumatoid arthritis, even the metabolic disorders. Cathepsin C (CTSC), as a member of the papain family of cysteine proteases, is a key enzyme in the activation of granule serine proteases thereby involved in modulating the inflammatory responses. Moreover, abundant expression of CTSC has been found in M1 macrophages in plaques of atherosclerosis and related to the progression of disease. However, whether CTSC can regulate macrophage activation status in inflammatory responses has not been fully investigated. In the present study, using peritoneal macrophages (PMs) and mouse macrophage cell line RAW264.7 treated with LPS and active monomer of CTSC, we found that CTSC was not only expressed in macrophages in M1 activation status, but also facilitated macrophages towards M1 phenotype, suggesting a self-activation mechanism involved in this process which may lead to a vicious circle in chronic inflammation. Then we attempted to explore the underlying molecular mechanisms of CTSC resulting in M1 activation. Focal adhesion kinase (FAK) is one of the non-receptor cytoplasmic protein tyrosine kinases, serving as an upstream mediator that leads to transcription of many pro-inflammatory factors. We found FAK expression was up-regulated at both mRNA and protein levels following CTSC stimulation, and FAK phosphorylation level was also significantly increased. The p38MAPK/NF-κB pathway, as the downstream of FAK, were also found activated in CTSC-treated macrophages, suggesting that CTSC may promote macrophage towards M1 activation status through FAK-induced p38MAPK/NF-κB signaling pathway activation. Our study provides a new therapeutic target in the treatment of chronic inflammatory diseases.

A rare case of giant multicystic solitary fibrous tumor of the orbit.

Solitary fibrous tumor (SFT) is a rare spindle cell tumor of the orbit of mesenchymal origin. Though these tumors are mostly solid, partial or complete cystic changes can rarely occur. Only six such previous cases of cystic fibrous tumor of the orbit have been mentioned in the literature. We report a case of an elderly male who presented with a huge left sided medial orbital mass. Magnetic resonance imaging showed a predominant cystic orbital mass separated by septae and suggested a diagnosis of Hydatid cyst. The patient underwent complete excision of the mass and histopathology and immunohistochemistry were suggestive of cystic SFT. Cystic degeneration in SFT is extremely rare and can be a harbinger of malignancy, and pose risk of recurrence. Close follow up and monitoring is required for all such cases.