Mitochondria are one of the most crucial components of the cell. Aging has a critical impact on mitochondria. Various studies have shown that the relationship between aging and mitochondria is multifaceted. In this review, we focused on mitochondrial DNA mutations and their impact on the cardiovascular system during aging and oxidative stress. While mitochondria contain their own DNA, part of their proteome is encoded by nuclear DNA, which further complicates the inheritance of mitochondrial diseases, making almost all methods of transmission of various pathologies possible. We provide a discussion on mitochondrial DNA mutagenesis and the most common problems associated with mitochondrial DNA mutations.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was introduced into cytopathology practice more than 5 years ago. It classifies the salivary gland lesion into 6 diagnostic categories and provides the risk of malignancy (ROM) and clinical management guidelines for each category. More than 100 articles have confirmed the applicability of this reporting system in routine practice and its important role in providing a uniform reporting system for salivary gland fine-needle aspiration. At the same time, new questions and feedback for improvement have emerged, as well as opportunities for clarification. For example, questions related to the non-diagnostic category are multiple-fold. First, although the cytologic criterion of the non-diagnostic category is currently defined as “<60 lesional cells or normal salivary gland tissue within the clinical setting of an evident mass”, this has not been established or validated in the literature. Second, the ROM for the non-diagnostic category is high. Another question surrounds the interesting topic of sub-classifying current MSRSGC categories, as the risk of malignancy could vary in tumors of the same category. The last one concerns the incorporation of the ever-increasing number of molecular markers and antibody detection of gene re-arrangements, so-called next-generation immunohistochemistry (IHC) markers, into routine cytopathology practice. The quick application of next-generation sequencing into pathology practice provides an exciting opportunity for salivary gland cytopathology diagnosis.

Artificial intelligence (AI) with machine learning tools are used to search, store, and analyze medical data to benefit both physicians and the health of patients in various ways. With the advancement in machine learning algorithms and bioinformatics techniques, AI has become an essential part of modern healthcare society. AI algorithms and deep learning applications support clinicians with managing health records, making diagnoses and clinical decisions, prescribing medication, determining mental health, and imaging analysis. Clinicians gain rapid access to information and research relevant to the needs of the patients. As some algorithms compete with and sometimes outperform clinicians, it is necessary to fully integrate this technology into daily medical practices. However, we must recognize the strengths and weaknesses of AI, and obtain the perspectives of experts outside the medical field to enable the inclusion of the ethical, philosophical, sociological, psychological, behavioral, and economical aspects of machine behavior when understanding the evolving interaction of machines with humans, so that it can be used for advantageous purposes. AI technology cannot be considered a replacement for physicians, rather it can act as multiple task-oriented device support to ease the burden on clinicians so that they can provide better care of life to patients at every level.

Hepatitis B virus (HBV) is a widely prevalent liver infection that can cause acute or chronic hepatitis. Although current treatment modalities are highly effective in the suppression of viral levels, they cannot eliminate the virus or achieve definitive cure. This is a consequence of the complex nature of HBV-host interactions. Major challenges to achieving sustained viral suppression include the presence of a high viral burden from the HBV DNA and hepatitis B surface antigen (HBsAg), the presence of reservoirs for HBV replication and antigen production, and the HBV-impaired innate and adaptive immune response of the host. Those therapeutic methods include cell entry inhibitors, HBsAg inhibitors, gene editing approaches, immune-targeting therapies and direct inhibitors of covalently closed circular DNA (cccDNA). Novel approaches that target these key mechanisms are now being studied in preclinical and clinical phases. In this review article, we provide a comprehensive review on mechanisms by which HBV escapes elimination from current treatments, and highlight new agents to achieve a definitive HBV cure.

Traditional Chinese Medicine has been implemented in clinical practice for thousands of years to treat rheumatoid arthritis (RA). Aconitum carmichaelii Debx (Fuzi) and Paeonia lactiflora Pall (Baishao) are a common herb-pair that is used in many herbal prescriptions to treat RA. However, the mechanism of Fuzi and Baishao for treating RA remains unclear. Here, we used a systems pharmacology and molecular docking approach to investigate the mechanism of Fuzi and Baishao in the treatment of RA.

We obtained active compounds and targets through a database search and manual supplementation, followed by network construction and protein-protein interaction construction, which were then verified using molecular docking, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses.

We obtained 56 active compounds (including a duplicate compound), 102 targets, and 54 pathways using our systems approach. The results indicate that both herbs are involved in IL-17 and tumor necrosis factor signaling pathways through albumin, interleukin-6, glyceraldehyde-3-phosphate dehydrogenase, epidermal growth factor receptor, prostaglandin-endoperoxide synthase 2, and other targets in the treatment of RA. After the combination, the number of targets, pathways, and specific targets on pathways increased.

This research provides new insight into this particular herb pair and novel research directions for the treatment of RA with Fuzi and Baishao.

Despite advances in current treatment options, Hepatocellular Carcinoma (HCC) recurrence still presents as a significant clinical challenge. After initial treatment, HCC recurrence occurs in a considerable portion of patients without an available standardized protocol for managing such an incident. Recurrence of advanced liver disease may make surgical treatment options impossible, in which case, locoregional therapy should be considered as an alternative. This review article discusses recurrent HCC after initial treatment and available non-surgical treatment options. Along with systemic therapy, liver-targeted therapies for recurrent HCC including, radiofrequency, microwave ablation, transarterial chemoembolization, and stereotactic body radiation therapy are promising options. Thermal ablation with radiofrequency or microwave ablation is a suitable treatment option for patients who experience smaller tumor recurrences but are not operable because of comorbidities, impaired liver functions, or tumor locality. Transarterial chemoembolization or radioembolization using Yttrium-90 can be used for patients with an incurable disease and have comparatively low adverse effects.

Nonalcoholic fatty liver disease (NAFLD) particularly affects patients with type 2 diabetes and obesity. The incidence of NAFLD has increased significantly over the last decades and is now pandemically across the globe. It is a complex systemic disease comprising hepatic lipid accumulation, inflammation, lipotoxicity, gut dysbiosis, and insulin resistance as main features and with the potential to progress to cirrhosis and hepatocellular carcinoma (HCC). In numerous animal and human studies the gut microbiota plays a key role in the pathogenesis of NAFLD, NAFLD-cirrhosis and NAFLD-associated HCC. Lipotoxicity is the driver of inflammation, insulin resistance, and liver injury. Likewise, western diet, obesity, and metabolic disorders may alter the gut microbiota, which activates innate and adaptive immune responses and fuels hereby hepatic and systemic inflammation. Indigestible carbohydrates are fermented by the gut microbiota to produce important metabolites, such as short-chain fatty acids and succinate. Numerous animal and human studies suggested a pivotal role of these metabolites in the progression of NAFLD and its comorbidities. Though, modification of the gut microbiota and/or the metabolites could even be beneficial in patients with NAFLD, NAFLD-cirrhosis, and NAFLD-associated HCC. In this review we collect the evidence that exogenous and endogenous hits drive liver injury in NAFLD and propel liver fibrosis and the progressing to advanced disease stages. NAFLD can be seen as the product of a complex interplay between gut microbiota, the immune response and metabolism. Thus, the challenge will be to understand its pathogenesis and to develop new therapeutic strategies.

We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid (tauro-THBA) in cholestasis.

Serum bile acid profiles were evaluated in 13 ABCB4-mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS). The concentration of tauro-THBA was compared between ABCB4-mutated patients with different prognoses. The areas under the curve (AUCs) of tauro-THBA were compared between ABCB11-mutated patients with native liver survival and those who died or underwent liver transplantation before 3 years of age by receiver operating characteristic curve (ROC), with another patient cohort for further verification.

The overall hydrophobicity indices of bile acids in ABCB4-mutated patients (12.99±3.25 m) were significantly lower than those of healthy controls (14.02±1.74 m, p<0.000). That was due to markedly increased bile acid modifications including conjugation, sulfation, and ketonization. Differences in the tauro-THBA concentration in ABCB4-mutated patients with different prognoses were not significant. ROC analysis indicated that levels of tauro-THBA of <60 nM yielded an AUC of 0.900 with a sensitivity of 80% and specificity of 87.5% for ABCB11-mutated patients with different prognoses (p=0.0192). Of the 15 patients with good prognosis, 14 were classified correctly and four of the five patients with a poor prognosis were classified correctly (14:15 vs. 1:5, p=0.005) with tauro-THBA as a classifier.

Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gamma-glutamyl transferase intrahepatic cholestasis patients.

Acinar cell carcinoma (ACC) of the pancreas is a rare malignant neoplasm with a poor prognosis. When in the pancreas, the diagnosis is relatively straightforward, based on characteristic cytomorphologic features and positive staining for acinar enzyme products such as trypsin and BCL10. However, ACC may occur in extra-pancreatic locations, where features overlapping with other entities can make the diagnosis challenging if not considered . Here, we report a case of pancreatic ACC that presented as a large splenic mass with a radiologically and grossly unremarkable pancreas. The patient was subsequently found to have a BRCA2 germline mutation. This case is presented to highlight an unusual presentation of ACC; review the cytopathologic, histologic, and immunohistochemical characteristics of ACC; and add to the literature associating ACC with BRCA2 mutations, which may have therapeutic and familial testing implications.

Several first-line immune checkpoint inhibitor (ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma (uHCC). This network meta-analysis (NMA) aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for uHCC.

A comprehensive literature search was performed in various databases from database inception to May 2022. The phase 3 trials evaluating first-line single-agent ICIs, molecular-target agents (MTAs), or their combinations in uHCC were included. The main endpoints were overall survival (OS) and progression-free survival (PFS). Pooled effect estimates were calculated using a random effects model within the frequentist framework. Subgroup analyses based on etiology were also conducted.

Twelve trials at low risk of bias with 8,275 patients comparing 13 treatments were included. OS with atezolizumab plus bevacizumab was comparable to sintilimab plus IBI305 [hazard ratio (HR): 1.16; 95% confidence interval (CI): 0.80–1.68] and camrelizumab plus apatinib (HR: 1.06; 95% CI: 0.75–1.51). The combination therapies, apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS, had higher P-score than single-agent MTAs or ICIs. The survival benefits were associated with a high risk of adverse events leading to treatment discontinuation. The proportion of patients with hepatitis B virus-related HCC receiving ICIs combinations might positively correlate with survival advantages (R2=0.8039, p=0.0155).

This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for uHCC. The optimal treatment algorithms should consider efficacy, safety, and etiology.

SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown.

Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated.

The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination.

The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.

Vaccine development has come center stage in the public domain given the extensive exposure it received during the COVID-19 pandemic. Although messenger RNA (mRNA) technology has been the focus of research and development efforts, particularly for oncology, for over three decades, its recent impact has enhanced the trajectory of vaccine development. mRNA technology is now at the forefront of enormous efforts focused on developing new vaccines against infectious diseases and cancer. This review outlines the current status of cancer vaccination and discusses its potential as a therapeutic modality.

The current paradigm presumes the higher the triglyceride level, the greater the probability of acne vulgaris (AV) occurrence or severity. However, this prevailing view lacks the necessary premises required to prove causality—for which the reverse should hold true: that low TG levels are predictive of less AV occurrence or severity. A low TG concentration in patients with AV has not yet been addressed, probably because of (i) the lack of any hypothesis connecting low TG levels to AV, and (ii) a lower prevalence of hypotriglyceridemia compared to hypertriglyceridemia in societies, which may lead to missing or misdiagnosis of other types of AV. Therefore, a formal or causal position statement cannot be issued. My observations on the high prevalence of severe cases of AV in a subgroup of individuals with extremely low levels of either serum TG or TC levels (between 40–60 mg/dl) encouraged me to share this experience. I suggest that studies investigating AV calculate—retrospectively or prospectively—the odds ratio of finding AV in people with extremely low levels of TG and/or TC. I further propose that researchers investigating different therapeutic approaches and medications in patients with AV measure relevant parameters/variables (such as those described in this paper) to yield necessary data for contemporary and future trials. The prevailing view, i.e., hyperlipidemia theory, lacks the necessary premises required to prove causality and should be revisited.

Because of its extraordinary phytomedicinal potential and numerous potential health benefits, lemongrass (Cymbopogon citratus), a well-known medicinal and aromatic plant, is of paramount significance. It is typically used as a drug replacement.

The present study was comprised of drying lemongrass into powder and determining the proximate and mineral composition, and then developing ethanolic extracts of powder to determine total phenolic contents (TPC), total flavonoid contents (TFC), total carotenoids (TC), and DPPH free radical scavenging activity. Next, lemongrass powder (LGP) was replaced at 0, 2.5, 5, 7.5, and 10% levels to develop nutritional biscuits.

The results revealed that lemongrass powder contained higher fiber (8.34 ± 0.04%) and ash (7.26 ± 0.06%) quantities, than wheat flour. Similarly, essential minerals Ca, Mg, K, Fe, and Zn contents in LGP were 36.80 ± 0.12, 64.89 ± 0.13, 54.65 ± 0.18, 12.68 ± 0.05, and 8.46 ± 0.07 mg/100 g dry weight, respectively, which were significantly higher than that calculated in wheat flour. Phytochemical analyses of lemongrass ethanolic extracts documented TPC as 240.46 ± 0.20 mg gallic acid equivalent/100 g, TFC as 98.45 ± 0.15 mg catechin equivalent/100 g, TC as 62.36 ± 0.12 mg/100 g, and DPPH activity as 60.18 ± 0.14 mg AAE/100 g, with such values being significantly higher than those in wheat flour.

Incorporation of LGP at different levels in wheat flour resulted in boosted phytochemical profiles of nutritional biscuits, but upon sensory evaluation of biscuits 2.5% level of LGP provided good scores for taste, flavor and overall acceptability, while for color and flavor 5% LGP was also found to be suitable with highest sensory scores.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern has been the dominant cause of worldwide COVID-19 cases since 2022. All Omicron sub-lineage viruses have demonstrated high transmissibility and an ability to escape vaccine-induced immunity. While first-generation vaccines, including monovalent vaccines, continue to provide protection against severe disease, hospitalization, and mortality, their efficacy against Omicron subvariants remains sparse. These vaccines have also been associated with rapidly waning protection against primary COVID-19 and COVID-19 reinfections conferred by evolving Omicron sub-lineages. This led to the development and deployment of updated vaccines and the introduction of the bivalent booster. Through this review, we highlight the brief journey of the variants of concern leading to the dominance of Omicron and the effectiveness of the key vaccines against these variants, including the updated (bivalent) boosters.

Plasma cell neoplasms are well-known for having diverse morphological and phenotype presentations and less commonly unusual immunophenotypical profiles. Such unexpected immunophenotypical variability could lead to inaccurate impressions upon initial assessment, thus delaying an accurate diagnosis. Here, the authors report seven plasma cell neoplasm cases with unusual morphology, immunophenotype, or unusual anatomic locations from the archives of Montefiore Medical Center Hematopathology department to highlight key considerations involved in diagnosing plasma cell neoplasms.

The authors reviewed the 2015 to 2022 electronic medical records at Montefiore Medical Center and identified seven plasma cell neoplasm cases with unusual immunophenotypes as well as anatomic localization. Clinical information including demographics, patient history, clinical presentation, and treatment was retrieved along with pertinent laboratory data. Cell morphology and immunohistochemistry were evaluated from formalin-fixed, paraffin-embedded biopsy specimens stained with hematoxylin and eosin (H&E). Morphologic features and immunophenotype determined by flow cytometry and immunohistochemistry were reviewed, along with molecular and cytogenetic studies.

The analysis of the cases underscores the diagnostic complexity associated with the diverse array of morphological and immunophenotypic features of plasma cell neoplasms and offers insight into overcoming diagnostic challenges while avoiding potential pitfalls.

Awareness of the spectrum of morphological and immunophenotypic variability in plasma cell neoplasms is key to avoiding misdiagnosing variants and delaying clinical workup. Correlation with clinical and laboratory findings and evaluation by immunostaining to confirm plasma cell origin is necessary to reach a correct diagnosis.

The liver is the largest glandular organ in the body and has a unique distribution of cells and biomolecules. However, the treatment outcome of end-stage liver disease is extremely poor. Single-cell sequencing is a new advanced and powerful technique for identifying rare cell populations and biomolecules by analyzing the characteristics of gene expression between individual cells. These cells and biomolecules might be used as potential targets for immunotherapy of liver diseases and contribute to the development of precise individualized treatment. Compared to whole-tissue RNA sequencing, single-cell RNA sequencing (scRNA-seq) or other single-cell histological techniques have solved the problem of cell population heterogeneity and characterize molecular changes associated with liver diseases with higher accuracy and resolution. In this review, we comprehensively summarized single-cell approaches including transcriptomic, spatial transcriptomic, immunomic, proteomic, epigenomic, and multiomic technologies, and described their application in liver physiology and pathology. We also discussed advanced techniques and recent studies in the field of single-cell; our review might provide new insights into the pathophysiological mechanisms of the liver to achieve precise and individualized treatment of liver diseases.

Liposomes are a potential drug delivery system involving encapsulation into a phospholipid-based vesicular carrier system. In comparison with conventional delivery systems, liposomes may be advantageous due to site-specific targeting, controlled release patterns, enhanced stability, and reduced associated toxicity, among other processes. Several researchers in the last decade have attempted to develop simple or modified forms of liposomes for the effective delivery of various types of therapeutic agents. This review is focused on a discussion about some of the recent literature on the medical application of liposomes. An account of the mode of action of different types of liposomes as a supporting basis for their superior therapeutic efficiency was provided. The application of liposomes in the delivery of anticancer, anti-bacterial, and anti-fungal drugs, among others, was discussed. Along with this discussion, liposomal carriers for the management of diseases related to the respiratory and nervous system were included along with a special emphasis on the outcomes of current literature. The information gathered through this review will be useful in furnishing ideas about the current status of research studies conducted on the formulation and development of liposomal carriers.