A review on microbes mediated resource recovery and bioplastic (polyhydroxyalkanoates) production from wastewater.

BACKGROUND: Plastic is widely utilized in packaging, frameworks, and as coverings material. Its overconsumption and slow degradation, pose threats to ecosystems due to its toxic effects. While polyhydroxyalkanoates (PHA) offer a sustainable alternative to petroleum-based plastics, their production costs present significant obstacles to global adoption. On the other side, a multitude of household and industrial activities generate substantial volumes of wastewater containing both organic and inorganic contaminants. This not only poses a threat to ecosystems but also presents opportunities to get benefits from the circular economy. Production of bioplastics may be improved by using the nutrients and minerals in wastewater as a feedstock for microbial fermentation. Strategies like feast-famine culture, mixed-consortia culture, and integrated processes have been developed for PHA production from highly polluted wastewater with high organic loads. Various process parameters like organic loading rate, organic content (volatile fatty acids), dissolved oxygen, operating pH, and temperature also have critical roles in PHA accumulation in microbial biomass. Research advances are also going on in downstream and recovery of PHA utilizing a combination of physical and chemical (halogenated solvents, surfactants, green solvents) methods. This review highlights recent developments in upcycling wastewater resources into PHA, encompassing various production strategies, downstream processing methodologies, and techno-economic analyses. SHORT CONCLUSION: Organic carbon and nitrogen present in wastewater offer a promising, cost-effective source for producing bioplastic. Previous attempts have focused on enhancing productivity through optimizing culture systems and growth conditions. However, despite technological progress, significant challenges persist, such as low productivity, intricate downstream processing, scalability issues, and the properties of resulting PHA.

Cisternostomy - As An Adjuvant Or Standalone Approach For Management Of Traumatic Brain Injury: A Systematic Review And Network Meta-Analysis.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of morbidity in all age groups worldwide. Decompressive craniectomy (DC) is a salvage procedure in patients with TBI. Outcome and quality of life following DC is questionable. Basal cisternostomy (BC) has been proposed to reduce edema and leads to brain relaxation. It was initially used as an adjunct in TBI patients, thereby improving outcome. With gaining popularity among the neurosurgeons, BC was used as a standalone approach in TBI patients. The aim of this network meta-analysis is to analyse the role of BC either as an adjunct or as a standalone approach in managing TBI patients. METHODS: A comprehensive search of electronic databases (PubMed and SCOPUS) was performed using the search strategy using the field terms and medical subheading terms (MeSH Terms) to retrieve studies describing the role of BC in patients with TBI either as an adjunct with DC or standalone treatment and their outcome. RESULTS: Thirty-one articles were selected for full text review and eighteen articles were selected for the final analysis. BC alone group were found to have minimum in-hospital mortality (odds ratio [OR], 0.348; 95% credible interval [CrI], 0.254 to 0.477) followed by DC combined with BC group (OR, 0.645; 95% CrI, 0.476 to 0.875). DC combined with BC group were found to have minimum duration of mechanical ventilation (OR, 0.114; 95% CrI, 0.005 to 2.451) followed by BC alone group (OR, 0.604; 95% CrI, 0.024 to 15.346). DC combined with BC group were found to have maximum Glasgow outcome scale (GOS) (OR, 1.661; 95% CrI, 0.907 to 3.041) followed by BC alone group (OR, 1.553; 95% CrI, 0.907 to 3.041). CONCLUSION: Our analysis showed that BC alone was associated with lower in-hospital mortality rates in TBI patients. DC with BC had decreased requirement of mechanical ventilation. However, larger multicentric studies from other parts of the world are required to confirm these findings.

The potential of genome editing to create novel alleles of resistance genes in rice.

Rice, a staple food for a significant portion of the global population, faces persistent threats from various pathogens and pests, necessitating the development of resilient crop varieties. Deployment of resistance genes in rice is the best practice to manage diseases and reduce environmental damage by reducing the application of agro-chemicals. Genome editing technologies, such as CRISPR-Cas, have revolutionized the field of molecular biology, offering precise and efficient tools for targeted modifications within the rice genome. This study delves into the application of these tools to engineer novel alleles of resistance genes in rice, aiming to enhance the plant's innate ability to combat evolving threats. By harnessing the power of genome editing, researchers can introduce tailored genetic modifications that bolster the plant's defense mechanisms without compromising its essential characteristics. In this study, we synthesize recent advancements in genome editing methodologies applicable to rice and discuss the ethical considerations and regulatory frameworks surrounding the creation of genetically modified crops. Additionally, it explores potential challenges and future prospects for deploying edited rice varieties in agricultural landscapes. In summary, this study highlights the promise of genome editing in reshaping the genetic landscape of rice to confront emerging challenges, contributing to global food security and sustainable agriculture practices.

Surgical Management of Extradural Tumors at the Cranio-Vertebral Junction - Insights from a Tertiary Care Centre.

BACKGROUND: Craniovertebral junction tumors are challenging due to their unique anatomical location. This study aimed to evaluate the complexities in dealing with such precarious craniovertebral junction extradural lesions over the decade. METHODS: 27 patients of extradural CVJ tumors operated between 2009-2018 were included. The demographic details, neurological status, surgical approach, extent of resection, type of fixation, complications and outcome at final follow-up were recorded for each patient. RESULTS: The mean age of the patients was 39.5 +/- 20 years. Most (17/27) of the patients had involvement of a single level. Clivus was the most common (9/17) involved region followed by atlas (7/17) vertebrae. Majority of the patients (13/27) were operated through the posterior-only approach. About 15 patients (55.5%) had instability or extensive lesions that necessitated posterior fixation. None of the patients underwent anterior fixation. Gross and near total excision were achieved in 10 patients (37%) and 3 patients (11 %) respectively while 14 patients underwent subtotal excision of tumor. On histopathological analysis, clival chordoma (8/27) was found to be the most common pathology followed by giant cell tumor (6/27), plasmacytoma (4/27) and multiple myeloma (2/27). Most patients (13 out of 27) had the same neurological status after the surgery. Six patients (22%) improved post-operatively with decreased weakness and spasticity. Thirteen (48%) patients underwent adjuvant radiotherapy. CONCLUSION: This retrospective study provides valuable insights into managing extradural CVJ tumors and highlights the importance of individualized approaches for optimal outcome.

Outcomes of endoscopic ultrasound-guided gallbladder drainage: A multicenter study from India (with video).

BACKGROUND: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) offers a safe and minimally invasive alternative for percutaneous cholecystostomy (PCC) in acute cholecystitis patients with high-surgical risk. Additionally, EUS-GBD serves as a rescue biliary drainage in malignant distal biliary obstruction. Despite its widespread application, data within the Indian context remains sparse. This study aims to report the outcomes of EUS-GBD through the first multi-center study from India. METHODS: We retrospectively analyzed patients undergoing EUS-GBD at six tertiary care centers of India from March 2022 to November 2023. EUS-GBD was performed by free hand or over-the-guidewire technique with lumen-apposing metal stent (LAMS) or large caliber metal stent (LCMS). The primary outcome was technical success (defined as successful deployment of stent between gallbladder and stomach/duodenal lumen). The secondary outcomes were clinical success (defined as resolution of symptoms of acute cholecystitis and more than > 50% reduction in bilirubin level within two weeks in distal biliary obstruction), adverse event rate, 30-day mortality rate and 90-day reintervention rate. RESULTS: Total 29 patients (mean age 65.86 ± 12.91, 11 female) underwent EUS-GBD. The indication for EUS-GBD were acute cholecystitis (79.31%) and rescue biliary drainage for malignant distal biliary obstruction (20.69%). LAMS was deployed in 92.86%, predominantly by free-hand technique (78.57%). Technical and clinical success rates were 96.55% and 82.75%, respectively. Adverse events occurred in 27.59% patients, with severe adverse events (bile leak and bleeding) being uncommon (10%). Both 30-day mortality rate and 90-day reintervention rate were 13.79% in patients. Cholecysto-duodenal fistula facilitated cholecystoscopic intervention and stone removal in one patient and transgastric EUS-GBD did not hamper bilio-enteric anastomosis during Whipple surgery in two patients. CONCLUSION: EUS-GBD is a safe and effective technique for managing acute cholecystitis in high-risk patients and for biliary drainage in cases with malignant distal biliary obstruction.

Unlocking the potential of flavonoid-based co-crystal and co-amorphous systems.

Flavonoids are polyphenolic compounds that have multiple benefits in treating various life-threatening diseases. Despite their diverse pharmacological activities, the market potential of flavonoids is hampered due to their poor solubility and low bioavailability after oral administration. The current review highlights the role of co-crystals and co-amorphous systems (CAMs) in enhancing the solubility, permeability, bioavailability, and therapeutic efficacy of flavonoids. It also explains the significance of flavonoid-based co-formers in the formation of co-crystals and CAMs with other APIs to improve their efficacy. Future perspectives, patented formulations, commercial medications (including their phases of clinical trials), and challenges associated with the use of flavonoid-based co-crystals and CAMs are also mentioned in the review.

Naringenin-Zinc Oxide Nanocomposites Amalgamated Polymeric Gel Augmented Drug Delivery and Attenuated Experimental Cutaneous Candidiasis in Balb/c Mice: In Vitro and In Vivo Studies.

Naringenin (NRG) inhibits the fungal 17ß-hydroxysteroid dehydrogenase accountable for ergosterol synthesis in Candida albicans (C. albicans), a causative agent for cutaneous candidiasis. In present research, NRG was complexed with ZnO nanomaterial (NRG-Zn2+) to synthesize NRG-Zn2+ nanocomposites. The particle size and ζ-potential of NRG-Zn2+ nanocomposites were respectively estimated to be 180.33 ± 1.22-nm and - 3.92 ± 0.35-mV. In silico data predicted the greater affinity of NRG-Zn2+ nanocomposite for 14α-demethylase and ceramide in comparison to NRG alone. Later, NRG-Zn2+ nanocomposites solution was transformed in to naringenin-zinc oxide nanocomposites loaded chitosan gel (NRG-Zn-CS-Gel) with viscosity and firmness of 854806.7 ± 52386.43 cP and 698.27 ± 10.35 g, respectively. The ex-vivo skin permeation demonstrated 70.49 ± 5.22% skin retention, significantly greater (P < 0.05) than 44.48 ± 3.06% of naringenin loaded chitosan gel (NRG-CS-Gel) and 31.24 ± 3.28% of naringenin solution (NRG Solution). NRG-Zn-CS-Gel demonstrated 6.71 ± 0.84% permeation of NRG with a flux value of 0.046 ± 0.01-µg/cm2/h. The MIC50 of NRG-Zn-CS-Gel against C. albicans was estimated to be 0.156-µg/mL with FICI (fractional inhibitory concentration index) of 0.018 that consequently exhibited synergistic efficacy. Further, NRG-Zn-CS-Gel demonstrated superior antifungal efficacy in C. albicans induced cutaneous candidiasis infection in Balb/c mice. The fungal burden in NRG-Zn-CS-Gel treated group was 109 ± 25 CFU/mL, significantly lower (P < 0.05) than positive control (2260 ± 446 CFU/mL), naringenin loaded chitosan gel (NRG-CS-Gel; 928 ± 127 CFU/mL) and chitosan gel (CS-Gel; 2116 ± 186 CFU/mL) treated mice. Further, histopathology examination and cytokine profiling of TNF-α, IL-1ß and IL-10 revealed the healing of skin and inflammation associated with cutaneous candidiasis infection. In conclusion, NRG-Zn-CS-Gel may be a potential candidate for translating in to a clinical viable topical nanotherapeutic.

Endobronchial Inflammatory Myofibroblastic Tumour Masquerading as a Ruptured Hydatid Cyst.

Inflammatory myofibroblastic tumours (IMTs) represent a rare group of neoplastic lesions characterized by a diverse clinical presentation. Endobronchial involvement is infrequently reported, and its manifestation mimicking the symptoms of a ruptured hydatid cyst adds an additional layer of complexity to the diagnostic challenge. This case report delves into an exceptional clinical scenario where an endobronchial IMT masqueraded as a ruptured hydatid cyst, initially confounding the diagnostic team. Through a detailed examination of the patient's clinical history, radiological imaging, bronchoscopy findings and subsequent histopathological analysis, we aim to contribute to the existing medical literature and shed light on the nuances encountered in accurately identifying and differentiating these two entities.

Emerging In Vitro and In Vivo Models: Hope for the Better Understanding of Cancer Progression and Treatment.

Various cancer models have been developed to aid the understanding of the underlying mechanisms of tumor development and evaluate the effectiveness of various anticancer drugs in preclinical studies. These models accurately reproduce the critical stages of tumor initiation and development to mimic the tumor microenvironment better. Using these models for target validation, tumor response evaluation, resistance modeling, and toxicity comprehension can significantly enhance the drug development process. Herein, various in vivo or animal models are presented, typically consisting of several mice and in vitro models ranging in complexity from transwell models to spheroids and CRISPR-Cas9 technologies. While in vitro models have been used for decades and dominate the early stages of drug development, they are still limited primary to simplistic tests based on testing on a single cell type cultivated in Petri dishes. Recent advancements in developing new cancer therapies necessitate the generation of complicated animal models that accurately mimic the tumor's complexity and microenvironment. Mice make effective tumor models as they are affordable, have a short reproductive cycle, exhibit rapid tumor growth, and are simple to manipulate genetically. Human cancer mouse models are crucial to understanding the neoplastic process and basic and clinical research improvements. The following review summarizes different in vitro and in vivo metastasis models, their advantages and disadvantages, and their ability to serve as a model for cancer research.

SPACe (Swift Phenotypic Analysis of Cells): an open-source, single cell analysis of Cell Painting data.

Phenotypic profiling by high throughput microscopy has become one of the leading tools for screening large sets of perturbations in cellular models. Of the numerous methods used over the years, the flexible and economical Cell Painting (CP) assay has been central in the field, allowing for large screening campaigns leading to a vast number of data-rich images. Currently, to analyze data of this scale, available open-source software ( i.e. , CellProfiler) requires computational resources that are not available to most laboratories worldwide. In addition, the image-embedded cell-to-cell variation of responses within a population, while collected and analyzed, is usually averaged and unused. Here we introduce SPACe ( S wift P henotypic A nalysis of Ce lls), an open source, Python-based platform for the analysis of single cell image-based morphological profiles produced by CP experiments. SPACe can process a typical dataset approximately ten times faster than CellProfiler on common desktop computers without loss in mechanism of action (MOA) recognition accuracy. It also computes directional distribution-based distances (Earth Mover's Distance - EMD) of morphological features for quality control and hit calling. We highlight several advantages of SPACe analysis on CP assays, including reproducibility across multiple biological replicates, easy applicability to multiple (∼20) cell lines, sensitivity to variable cell-to-cell responses, and biological interpretability to explain image-based features. We ultimately illustrate the advantages of SPACe in a screening campaign of cell metabolism small molecule inhibitors which we performed in seven cell lines to highlight the importance of testing perturbations across models.

Outcomes of Decompressive Surgery for Patients With Severe Cerebral Venous Thrombosis: DECOMPRESS2 Observational Study.

BACKGROUND: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort. METHODS: DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression. RESULTS: A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery. CONCLUSIONS: Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation.

Novel treatment with double scope technique for disconnected pancreatic duct syndrome with external pancreatic fistula.

Background and study aims External pancreatic fistula in association with disconnected pancreatic duct syndrome is a common sequelae of the percutaneous step-up approach for infected pancreatic necrosis and is associated with significant morbidity. The present study aimed to report the initial outcome of a novel technique of two-scope guided tractogastrostomy for management of this condition. Patients and methods The present study was a retrospective analysis of data from patients with external pancreatic fistula and disconnected pancreatic duct syndrome, who underwent two-scope-guided tractogastrostomy. All the patients had a 24F or larger drain placed in the left retroperitoneum. Transgastric echo endoscopy and sinus tract endoscopy were performed simultaneously to place a stent between the gastric lumen and the sinus tract. Technical success was defined as placement of the stent between the tract and the stomach. Clinical success was defined as successful removal of the percutaneous drain without the occurrence of pancreatic fluid collection, ascites, external fistula, or another intervention 12 weeks after the procedure. Results Three patients underwent two scope-guided tractogastrostomy. Technical and clinical success were achieved in all the patients. No procedure-related side effects or recurrence occurred in any of the patients. Conclusions Two-scope-guided tractogastrostomy for treatment of external pancreatic fistula due to disconnected pancreatic duct syndrome is a feasible technique and can be further evaluated.

High mobility group box 1 cytokine targeted topical delivery of resveratrol embedded nanoemulgel for the management of atopic dermatitis.

Resveratrol is a polyphenolic compound showing anti-inflammatory activity by inhibition of high mobility group box 1 cytokine responsible for the activation of nuclear factor-κB pathway in atopic dermatitis. To evaluate the efficacy of resveratrol through topical route we have developed resveratrol-loaded nanoemulgel for the effective management of atopic dermatitis in mice model. The resveratrol-loaded nanoemulsion (0.5%, 0.75% and 1% w/w) was optimized by spontaneous nano-emulsification. The optimized resveratrol-loaded nanoemulsions showed average globule size in the 180-230 nm range and found to be monodispersed. The resveratrol nanoemulgel was prepared with a SEPINEO™ P 600 gel base and propylene glycol. Ex vivo permeation and retention study resulted in significantly higher skin retention of resveratrol from resveratrol-loaded nanoemulgel than free resveratrol-loaded gel. Preclinical efficacy of resveratrol nanoemulgel displayed promising therapeutic outcomes where, western blotting of skin tissues disclosed a significant reduction in the relative expression of high mobility group box 1, the receptor for advanced glycation end products, toll-like receptor-4 and phosphorylated nuclear factor-κB. Further, real-time polymerase chain reaction also disclosed a significant reduction in pro-inflammatory cytokines such as thymic stromal lymphopoietin, interleukin-4, interleukin-13, interleukin-31, tumor necrosis factor-α and interleukin-6. The histopathological examination of skin sections showed improvement in the skin condition. Collectively, the findings from our study showcased the significant improvement in the atopic dermatitis skin condition in mice model after topical application of resveratrol loaded nanoemulgel.

Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2-SP1-SAT1 axis.

The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP-seq and RNA-seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated acetylation of SP1 at the lysine 19 residue that increased SP1 protein stability and transcriptional activity. Genetic or pharmacologic inhibition of the ACSS2-SP1-SAT1 axis diminished the tumour burden in mouse models. These results reveal that the metabolic flexibility imparted by the stroma-derived acetate enabled cancer cell survival under acidosis via the ACSS2-SP1-SAT1 axis.

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta.

The initial step in estrogen-regulated transcription is the binding of a ligand to its cognate receptors, named estrogen receptors (ERα and ERß). Phytochemicals present in foods and environment can compete with endogenous hormones to alter physiological responses. We screened 224 flavonoids in our engineered biosensor ERα and ERß PRL-array cell lines to characterize their activity on several steps of the estrogen signaling pathway. We identified 83 and 96 flavonoids that can activate ERα or ERß, respectively. While most act on both receptors, many appear to be subtype-selective, including potent flavonoids that activate ER at sub-micromolar concentrations. We employed an orthogonal assay using a transgenic zebrafish in vivo model that validated the estrogenic potential of these compounds. To our knowledge, this is the largest study thus far on flavonoids and the ER pathway, facilitating the identification of a new set of potential endocrine disruptors acting on both ERα and ERß.

The MUC1-HIF-1α signaling axis regulates pancreatic cancer pathogenesis through polyamine metabolism remodeling.

Dysregulation of polyamine metabolism has been implicated in cancer initiation and progression; however, the mechanism of polyamine dysregulation in cancer is not fully understood. In this study, we investigated the role of MUC1, a mucin protein overexpressed in pancreatic cancer, in regulating polyamine metabolism. Utilizing pancreatic cancer patient data, we noted a positive correlation between MUC1 expression and the expression of key polyamine metabolism pathway genes. Functional studies revealed that knockdown of spermidine/spermine N1-acetyltransferase 1 (SAT1), a key enzyme involved in polyamine catabolism, attenuated the oncogenic functions of MUC1, including cell survival and proliferation. We further identified a regulatory axis whereby MUC1 stabilized hypoxia-inducible factor (HIF-1α), leading to increased SAT1 expression, which in turn induced carbon flux into the tricarboxylic acid cycle. MUC1-mediated stabilization of HIF-1α enhanced the promoter occupancy of the latter on SAT1 promoter and corresponding transcriptional activation of SAT1, which could be abrogated by pharmacological inhibition of HIF-1α or CRISPR/Cas9-mediated knockout of HIF1A. MUC1 knockdown caused a significant reduction in the levels of SAT1-generated metabolites, N1-acetylspermidine and N8-acetylspermidine. Given the known role of MUC1 in therapy resistance, we also investigated whether inhibiting SAT1 would enhance the efficacy of FOLFIRINOX chemotherapy. By utilizing organoid and orthotopic pancreatic cancer mouse models, we observed that targeting SAT1 with pentamidine improved the efficacy of FOLFIRINOX, suggesting that the combination may represent a promising therapeutic strategy against pancreatic cancer. This study provides insights into the interplay between MUC1 and polyamine metabolism, offering potential avenues for the development of treatments against pancreatic cancer.

eEF1A2 promotes PTEN-GSK3ß-SCF complex-dependent degradation of Aurora kinase A and is inactivated in breast cancer.

The translation elongation factor eEF1A promotes protein synthesis. Its methylation by METTL13 increases its activity, supporting tumor growth. However, in some cancers, a high abundance of eEF1A isoforms is associated with a good prognosis. Here, we found that eEF1A2 exhibited oncogenic or tumor-suppressor functions depending on its interaction with METTL13 or the phosphatase PTEN, respectively. METTL13 and PTEN competed for interaction with eEF1A2 in the same structural domain. PTEN-bound eEF1A2 promoted the ubiquitination and degradation of the mitosis-promoting Aurora kinase A in the S and G2 phases of the cell cycle. eEF1A2 bridged the interactions between the SKP1-CUL1-FBXW7 (SCF) ubiquitin ligase complex, the kinase GSK3ß, and Aurora-A, thereby facilitating the phosphorylation of Aurora-A in a degron site that was recognized by FBXW7. Genetic ablation of Eef1a2 or Pten in mice resulted in a greater abundance of Aurora-A and increased cell cycling in mammary tumors, which was corroborated in breast cancer tissues from patients. Reactivating this pathway using fimepinostat, which relieves inhibitory signaling directed at PTEN and increases FBXW7 expression, combined with inhibiting Aurora-A with alisertib, suppressed breast cancer cell proliferation in culture and tumor growth in vivo. The findings demonstrate a therapeutically exploitable, tumor-suppressive role for eEF1A2 in breast cancer.

Metabolomic Investigations into Hypoxia-Mediated Metabolic Reprogramming of Pancreatic Cancer Cells.

Hypoxia is a crucial microenvironmental factor that defines tumor cell growth and aggressiveness. Cancer cells adapt to hypoxia by altering their metabolism. These alterations impact various cellular and physiological functions, including energy metabolism, vascularization, invasion and metastasis, genetic instability, cell immortalization, stem cell maintenance, and resistance to chemotherapy (Li et al. Technol Cancer Res Treat 20:15330338211036304, 2021). Hypoxia-inducible factor-1α (HIF-1α) is known to be a critical regulator of glycolysis that directly regulates the transcription of multiple key enzymes of the glycolysis pathway. Moreover, HIF-1α stabilization can be directly modulated by TCA-derived metabolites, including 2-ketoglutarate and succinate (Infantino et al, Int J Mol Sci 22(22), https://doi.org/10.3390/ijms22115703 , 2021). Overall, the molecular mechanisms underlying the adaptation of cellular metabolism to hypoxia impact the metabolic phenotype of cancer cells. Such adaptations include increased glucose uptake, increased lactate production, and increased levels of other metabolites that stabilize HIF-1α, leading to a vicious circle of hypoxia-induced tumor growth.