Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma.

LINE-1 (L1) retrotransposons are mobile genetic elements comprising ~17% of the human genome. New L1 insertions can profoundly alter gene function and cause disease, though their significance in cancer remains unclear. Here, we applied enhanced retrotransposon capture sequencing (RC-seq) to 19 hepatocellular carcinoma (HCC) genomes and elucidated two archetypal L1-mediated mechanisms enabling tumorigenesis. In the first example, 4/19 (21.1%) donors presented germline retrotransposition events in the tumor suppressor mutated in colorectal cancers (MCC). MCC expression was ablated in each case, enabling oncogenic ß-catenin/Wnt signaling. In the second example, suppression of tumorigenicity 18 (ST18) was activated by a tumor-specific L1 insertion. Experimental assays confirmed that the L1 interrupted a negative feedback loop by blocking ST18 repression of its enhancer. ST18 was also frequently amplified in HCC nodules from Mdr2(-/-) mice, supporting its assignment as a candidate liver oncogene. These proof-of-principle results substantiate L1-mediated retrotransposition as an important etiological factor in HCC.

Factors associated with appointment 'no-shows' at two tertiary level outpatient oculoplastic clinics.

PURPOSE: Appointment no-shows in clinics can adversely impact patients and physicians alike. This study aimed to determine the rate and potential causes of missed appointments in oculoplastic clinics and compare a private practice and hospital-based academic setting. METHODS: A retrospective review of patients who booked appointments for oculoplastic consultation, between August 2019 and January 2020 at two oculoplastic clinics was performed. Demographic and patient-specific characteristics of patients who failed to attend their appointment were identified. Data were analysed to determine and compare the no-show rates in both clinics and logistic regression was performed to determine factors associated with them. RESULTS: The rate of missed appointments was 3% and 17% at the oculoplastic clinics of Lions Eye Institute (LEI, private practice) and Albany Medical Center (AMC, academic hospital-based office), respectively. Patients at the AMC clinic were more likely to be male, younger, have a lower household income, not carry private insurance, and suffer from trauma. Logistic regression analysis showed lower patient age to significantly increase the likelihood of no-shows in both clinics (p = .01 for LEI, p = .003 for AMC), and lead appointment time greater than 90 days to be a significant risk factor for no-shows at LEI (p = .01). CONCLUSIONS: The no-show rate for oculoplastic appointments is 3% and 17% at LEI and AMC clinics, respectively. Our analysis shows that younger patients are more likely to miss appointments at both clinics, and an appointment lead time greater than 90 days is a significant risk factor for no-shows at LEI.

Emerging Field of Nanotechnology in Environment.

The art of utilizing and manipulating micro materials have been dated back to antient era. With the advancement in technologies, the state-of-art methods of nano technologies and nano sciences has been employed in various sectors including environment, product designing, food industry, pharmaceuticals industries to way out solve standard problem of mankind. Due to rapid industrialization and the alarming levels of pollution there has been an urgent need to address the environmental and energy issues. Environmental sustainability concerns the global climate change and pollution including air, water, soil. The field of nanotechnology has proven to be a promising field where sensing and remediation, have been dramatically advanced by the use of nanomaterials. This emergent science of surface to mass ratio is the principle theorem for manipulating structure at molecular levels. The review sums up all the advancements in the field of nanotechnology and their recent application in the environment. New opportunities and challenges have also been discussed in detail to understand the use of nanotechnology as problem-to-solution ratio. Graphical abstract: Image depicting the application of nanotechnology in environmental concerns. The combinations of technologies like bioremediations, bioaugmentations with state-of-the-art nanotechnology like carbon nanotubes and Nano capsules to answer the environmental challenges of soil quality, and plant productivity.

4q-D4Z4 chromatin architecture regulates the transcription of muscle atrophic genes in facioscapulohumeral muscular dystrophy.

Despite increasing insights in genome structure organization, the role of DNA repetitive elements, accounting for more than two thirds of the human genome, remains elusive. Facioscapulohumeral muscular dystrophy (FSHD) is associated with deletion of D4Z4 repeat array below 11 units at 4q35.2. It is known that the deletion alters chromatin structure in cis, leading to gene up-regulation. Here we show a genome-wide role of 4q-D4Z4 array in modulating gene expression via 3D nuclear contacts. We have developed an integrated strategy of 4q-D4Z4-specific 4C-seq and chromatin segmentation analyses, showing that 4q-D4Z4 3D interactome and chromatin states of interacting genes are impaired in FSHD1 condition; in particular, genes that have lost the 4q-D4Z4 interaction and with a more active chromatin state are enriched for muscle atrophy transcriptional signature. Expression level of these genes is restored by the interaction with an ectopic 4q-D4Z4 array, suggesting that the repeat directly modulates the transcription of contacted targets. Of note, the up-regulation of atrophic genes is a common feature of several FSHD1 and FSHD2 patients, indicating that we have identified a core set of deregulated genes involved in FSHD pathophysiology.

Early maternal care restores LINE-1 methylation and enhances neurodevelopment in preterm infants.

BACKGROUND: Preterm birth affects almost 9-11% of newborns and is one of the leading causes of childhood neurodevelopmental disabilities; the underlying molecular networks are poorly defined. In neurons, retrotransposons LINE-1 (L1) are an active source of genomic mosaicism that is deregulated in several neurological disorders; early life experience has been shown to regulate L1 activity in mice. METHODS: Very preterm infants were randomized to receive standard care or early intervention. L1 methylation was measured at birth and at hospital discharge. At 12 and 36 months, infants' neurodevelopment was evaluated with the Griffiths Scales. L1 methylation and CNVs were measured in mouse brain areas at embryonic and postnatal stages. RESULTS: Here we report that L1 promoter is hypomethylated in preterm infants at birth and that an early intervention program, based on enhanced maternal care and positive multisensory stimulation, restores L1 methylation levels comparable to healthy newborns and ameliorates neurodevelopment in childhood. We further show that L1 activity is fine-tuned in the perinatal mouse brain, suggesting a sensitive and vulnerable window for the L1 epigenetic setting. CONCLUSIONS: Our results open the field on the inspection of L1 activity as a novel molecular and predictive approach to infants' prematurity-related neurodevelopmental outcomes. TRIAL REGISTRATION: ClinicalTrial.gov ( NCT02983513 ). Registered on 6 December 2016, retrospectively registered.

Generation of a tissue-specific transgenic model for K8 phosphomutants: A tool to investigate the role of K8 phosphorylation during skin carcinogenesis in vivo.

Keratin 8/18, the predominant keratin pair of simple epithelia, is known to be aberrantly expressed in several squamous cell carcinomas (SCCs), where its expression is often correlated with increased invasion, neoplastic progression, and poor prognosis. The majority of keratin 8/18 structural and regulatory functions are governed by posttranslational modifications, particularly phosphorylation. Apart from filament reorganization, cellular processes including cell cycle, cell growth, cellular stress, and apoptosis are known to be orchestrated by K8 phosphorylation at specific residues in the head and tail domains. Even though deregulation of K8 phosphorylation at two significant sites (Serine73 /Serine431 ) has been implicated in neoplastic progression of SCCs by various in vitro studies, including ours, it is reported to be highly context-dependent. Therefore, to delineate the precise role of Kereatin 8 phosphorylation in cancer initiation and progression, we have developed the tissue-specific transgenic mouse model expressing Keratin 8 wild type and phosphodead mutants under Keratin 14 promoter. Subjecting these mice to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-mediated skin carcinogenesis revealed that Keratin 8 phosphorylation may lead to an early onset of tumors compared to Keratin 8 wild-type expressing mice. Conclusively, the transgenic mouse model developed in the present study ascertained a positive impact of Keratin 8 phosphorylation on the neoplastic transformation of skin-squamous cells.

TNF-Stimulated Gene-6 Is a Key Regulator in Switching Stemness and Biological Properties of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are well established to have promising therapeutic properties. TNF-stimulated gene-6 (TSG-6), a potent tissue-protective and anti-inflammatory factor, has been demonstrated to be responsible for a significant part of the tissue-protecting properties mediated by MSCs. Nevertheless, current knowledge about the biological function of TSG-6 in MSCs is limited. Here, we demonstrated that TSG-6 is a crucial factor that influences many functional properties of MSCs. The transcriptomic sequencing analysis of wild-type (WT) and TSG-6-/- -MSCs shows that the loss of TSG-6 expression leads to the perturbation of several transcription factors, cytokines, and other key biological pathways. TSG-6-/- -MSCs appeared morphologically different with dissimilar cytoskeleton organization, significantly reduced size of extracellular vesicles, decreased cell proliferative rate, and loss of differentiation abilities compared with the WT cells. These cellular effects may be due to TSG-6-mediated changes in the extracellular matrix (ECM) environment. The supplementation of ECM with exogenous TSG-6, in fact, rescued cell proliferation and changes in morphology. Importantly, TSG-6-deficient MSCs displayed an increased capacity to release interleukin-6 conferring pro-inflammatory and pro-tumorigenic properties to the MSCs. Overall, our data provide strong evidence that TSG-6 is crucial for the maintenance of stemness and other biological properties of murine MSCs.

Recent advances in the management of non-infectious posterior uveitis.

PURPOSE: To review the current regimens and novel therapeutic modalities in various stages of research and development for the management of non-infectious posterior uveitis (NIPU). METHODS: We performed a thorough review of current literature using PubMed, Google Scholar and Clinicaltrials.gov to identify the published literature about the available therapeutics and novel drugs/therapies in different stages of clinical trials. RESULTS: The current management regimen for non-infectious posterior uveitis includes corticosteroids, immunomodulatory therapies and anti-metabolites. However, NIPU requires long-term management for efficacious remission of the disease and to prevent disease relapse. Long-term safety issues associated with steroids have led to efforts to develop novel therapeutic agents including biological response modulators and immunosuppressants. The current therapeutic agents in various stages of development include calcineurin inhibitors, biologic response modifiers and a more a comprehensive modalities like ocular gene therapy as well as novel drug delivery mechanisms for higher bioavailability to the target tissues, with minimal systemic effects. CONCLUSION: Novel efficacious therapeutic modalities under development will help overcome the challenges associated with the traditional therapeutic agents.

Status and Prospects of Next Generation Sequencing Technologies in Crop Plants.

The history of DNA sequencing dates back to 1970s. During this period the two first generation nucleotide sequencing techniques were developed. Subsequently the Sanger's dideoxy method of sequencing gained popularity over Maxam and Gilbert's chemical method of sequencing. However, in the last decade, we have observed revolutionary changes in DNA sequencing technologies leading to the emergence of next-generation sequencing (NGS) techniques. NGS technologies have enhanced the throughput and speed of sequencing combined with bringing down the overall cost of the process over a time. The major applications of NGS technologies being genome sequencing and resequencing, transcriptomics, metagenomics in relation to plant-microbe interactions, exon and genome capturing, development of molecular markers and evolutionary studies. In this review, we present a broader picture of evolution of NGS tools, its various applications in crop plants, and future prospects of the technology for crop improvement.

Awareness of Biomedical Waste Management among Dentists associated with Institutions and Private Practitioners of North India: A Comparative Study.

AIM: The present study aimed to obtain information about knowledge, execution, and attitude toward biomedical waste (BMW) and its management. MATERIALS AND METHODS: In the present study, a self-administered closed-ended questionnaire was designed to conduct a cross-sectional survey. It was distributed among 614 dentists (institution associated or private practitioners) in the cities of North India. The questionnaire comprised 36 questions regarding knowledge, execution, and attitude toward BMW and its management. Frequency distribution and chi-square test along with paired t-test were used to compare the data obtained between the private practitioners and institution-associated dentists. RESULTS: The study showed that 80% private practitioners were aware of the categories of BMW as compared with 100% of institution-associated dentists. However, 41% dentists associated with institution were disposing the chemical waste directly into sewer and a surprising high number of private practitioners were discarding directly without any treatment. Furthermore, regarding the mandatory maintenance of BMW records, 100% institution-associated respondents were aware, whereas only 6.5% private practitioners knew about it. Regarding BMW management not frequently being followed, 78% of private practitioners believed extra burden as the reason. CONCLUSION: Most of the dentists had adequate knowledge regarding BMW policies and its management. Although it was being practiced in mostly all the institutes on a regular basis, the majority of private practitioners were not practicing it due to various reasons, such as financial burden, lack of availability of service, and poor attitude toward its management. CLINICAL SIGNIFICANCE: There is a need to make it compulsory and organize training sessions to educate the dental personnel and to establish the importance of proper management.

Quantitative phosphoproteomic analysis reveals system-wide signaling pathways regulated by site-specific phosphorylation of Keratin-8 in skin squamous cell carcinoma derived cell line.

Keratin 8/18, a simple epithelia specific keratin pair, is often aberrantly expressed in squamous cell carcinomas (SCC) where its expression is correlated with increased invasion and poor prognosis. Majority of Keratin 8 (K8) functions are governed by its phosphorylation at Serine73 (head-domain) and Serine431 (tail-domain) residues. Although, deregulation of K8 phosphorylation is associated with progression of different carcinomas, its role in skin-SCC and the underlying mechanism is obscure. In this direction, we performed tandem mass tag-based quantitative phosphoproteomics by expressing K8 wild type, phosphodead, and phosphomimetic mutants in K8-deficient A431 cells. Further analysis of our phosphoproteomics data showed a significant proportion of total phosphoproteome associated with migratory, proliferative, and invasive potential of these cells to be differentially phosphorylated. Differential phosphorylation of CDK1T14,Y15 , EIF4EBP1T46,T50 , EIF4BS422 , AKT1S1T246,S247 , CTTN1T401,S405,Y421 , and CAP1S307/309 in K8-S73A/D mutant and CTTN1T401,S405,Y421 , BUB1BS1043 , and CARHSP1S30,S32 in K8-S431A/D mutants as well as some anonymous phosphosites including MYCS176 , ZYXS344 , and PNNS692 could be potential candidates associated with K8 phosphorylation mediated tumorigenicity. Biochemical validation followed by phenotypic analysis further confirmed our quantitative phosphoproteomics data. In conclusion, our study provides the first global picture of K8 site-specific phosphorylation function in neoplastic progression of A431 cells and suggests various potential starting points for further mechanistic studies.

Ellis-van Creveld with an Unusual Dental Anomaly: A Case Report.

The Ellis-van Creveld (EVC) syndrome is a chondroectodermal dysplasia and is characterized by the cardinal features of disproportionate short stature, polydactyly, hidrotic ectodermal dysplasia, and congenital heart malformations, along with other skeletal and dental abnormalities. It is a rare condition, with very few cases reported in the medical literature. It is inherited as an autosomal recessive disorder with variable expressions, due to the mutation of the EVC syndrome 1 and 2 genes, which are located on chromosome 4p16. The present case report describes the EVC syndrome in a 14-year-old girl, who presented with a tetrad of all the cardinal features and other associated features. Additional unusual dental findings such as single-rooted funnel-shaped molars, reduced crown size, enamel hypoplasia, supernumerary teeth, dental fusion, taurodontism, abnormal occlusal anatomy with wide grooves, and atypical cusps have been reported in most previous cases of this syndrome. However, in our patient, surprisingly, the teeth present were relatively non-anomalous, both clinically and radiographically (i.e., with none of the usually found abnormalities mentioned above). The only abnormal dental findings were those of absent maxillary and mandibular incisors (including impacted permanent incisors) and mild malocclusion, a novel point of this case.

Network of Cancer Genes (NCG 3.0): integration and analysis of genetic and network properties of cancer genes.

The identification of a constantly increasing number of genes whose mutations are causally implicated in tumor initiation and progression (cancer genes) requires the development of tools to store and analyze them. The Network of Cancer Genes (NCG 3.0) collects information on 1494 cancer genes that have been found mutated in 16 different cancer types. These genes were collected from the Cancer Gene Census as well as from 18 whole exome and 11 whole-genome screenings of cancer samples. For each cancer gene, NCG 3.0 provides a summary of the gene features and the cross-reference to other databases. In addition, it describes duplicability, evolutionary origin, orthology, network properties, interaction partners, microRNA regulation and functional roles of cancer genes and of all genes that are related to them. This integrated network of information can be used to better characterize cancer genes in the context of the system in which they act. The data can also be used to identify novel candidates that share the same properties of known cancer genes and may therefore play a similar role in cancer. NCG 3.0 is freely available at http://bio.ifom-ieo-campus.it/ncg.

Comparison of Clinical Characteristics and Biomarkers in Culture-Positive and Culture-Negative Sepsis Patients.

OBJECTIVES: Sepsis is one of the leading causes of morbidity and mortality worldwide, and culture-negative sepsis, despite its prevalence, is largely understudied. The current study intends to examine clinical characteristics and biomarkers in culture-positive and culture-negative sepsis, focusing on 30-day mortality and duration of hospital stay in both groups.  Materials and methods: A prospective observational comparative cohort study was done on 150 patients admitted to the intensive care unit (ICU) and wards of Jaipur Golden Hospital. Patients with documented fungal, viral, or parasitic infections, as well as those who had undergone surgery or experienced trauma, were excluded.  Results: The mean age of the patients was 51.31±18.94 years. Of 150 patients, 95 (63.3%) were culture-negative, whereas 55 (36.7%) were culture-positive, with more men in the former and more women in the latter. Patients with negative cultures had fewer comorbidities. The levels of procalcitonin (PCT), C-reactive protein (CRP), and serum lactate were within the prescribed limit for both culture-negative and positive patients. A higher proportion (87.3%) of the organisms isolated from culture-positive individuals were gram-negative, with Escherichia coli (E. coli) having the highest prevalence (27.3%), followed by Klebsiella (20%). There were 12.7% gram-positive isolates. The culture-negative patients had significantly better outcomes (P=0.003) as well as the duration of hospital stay (P<0.001) than the culture-positive patients. Culture-positive patients had a more severe illness, a higher incidence of septic shock, and a higher fatality rate than culture-negative patients. CONCLUSION: It can be concluded that CRP and PCT can be used as clinically reliable sepsis biomarkers in both culture-positive and culture-negative patients. The study found that culture-negative sepsis is more prevalent and that there are substantial differences between culture-negative and culture-positive sepsis, with the former group having fewer comorbidities, less severe illness, a shorter duration of hospital stays, lower death rates, and better outcomes.

Concurrence of Ocular Cicatricial Pemphigoid in Chronic Ocular Graft-Versus-Host Disease.

PURPOSE: The aim of this study was to report a series of 3 patients with ocular graft-versus-host disease (oGVHD) with progressive cicatricial conjunctival changes who were diagnosed with ocular cicatricial pemphigoid (OCP) after conjunctival biopsy. METHODS: This study was a retrospective case series. RESULTS: Three patients who received hematopoietic stem cell transplantation for hematologic malignancies developed oGVHD and subsequently were diagnosed with OCP. Case 1 was a 73-year-old woman with oGVHD who developed symblepharon and showed positive IgA, IgG, and C3 staining of the basement membrane zone (BMZ) on conjunctival biopsy, consistent with OCP. She was systemically treated with tacrolimus and prednisone with resolution of conjunctival inflammation. Case 2 was a 68-year-old man with oGVHD who developed symblepharon, severe dry eye, and corneal epithelial defect. An initial conjunctival biopsy was negative, but a repeat biopsy performed 10 years later showed positive BMZ IgA and IgG staining. Healing of the epithelial defect was achieved after treatment with high-dose systemic cyclosporine. Case 3 was a 75-year-old woman with oGVHD who had a nonhealing corneal epithelial defect and symblepharon with positive IgA BMZ staining on conjunctival biopsy, consistent with OCP. The patient responded well to methotrexate with healing of the epithelial defect. CONCLUSIONS: Although low-grade conjunctival fibrotic changes may be observed in chronic oGVHD, development of severe and progressive cicatricial changes, including symblepharon formation, should prompt consideration of biopsy to rule out concurrent OCP, the management of which differs from that of oGVHD.

Statistical evaluation and positive predictive value of key features of periorbital basal cell carcinoma.

OBJECTIVE: To determine the accuracy of using the suspicious features of periorbital lesions-telangiectasias, madarosis, and ulceration-to identify basal cell carcinoma (BCC). This may impact whether a histopathologic confirmation is always necessary. METHODS: This retrospective review of patients who underwent biopsy of eyelid lesions was conducted over a five-year period, between 2015 and 2020 at a single clinical site. Specifically, the histopathologic diagnosis and the presence or absence of clinical signs of madarosis, ulceration and telangiectasia were recorded. The positive predictive value (PPV) for eyelid BCC and odds ratio of each of these clinical signs was calculated. RESULTS: 179 patients underwent incisional biopsies of eye lid lesions. Of the 79 patients with eyelid BCC, 96% had ulceration, 95% had madarosis, and 75% had telangiectasias over the lid lesion; this contrasted with the 3%, 4% and 6% respectively in the 100 patients with benign lid lesions. The PPV for eyelid BCC of ulceration was 95.0%, madarosis was 96.2% and telangiectasias was 90.8%. The presence of two or all three signs in a patient was strongly predictive of BCC (PPV=100%). CONCLUSION: The presence of two or more suspicious features almost ensures the accuracy of the suspected diagnosis of a BCC. This suggests that biopsy of eyelid lesions before complete surgical excision that demonstrate several defining features may not be necessary in all cases. However, lesions that do not demonstrate multiple explicit features that indicate a malignancy will still require histopathologic confirmation.

Reactivation of retinopathy of prematurity six years after intravitreal injection of bevacizumab.

Although intravitreal anti-vascular endothelial growth factor (VEGF) therapy is effective in the management of retinopathy of prematurity (ROP), reactivations following treatment are known to occur. We present the case of an asymptomatic child who developed a very late reactivation of ROP 6 years after its successful treatment with intravitreal bevacizumab. This case reemphasizes the importance of long-term follow-up after anti-VEGF therapy for ROP until retinal vascularization is complete. It also supports investigating the utility of laser photocoagulation for peripheral avascular retina after successful treatment with anti-VEGF injection for type I ROP.

Ocular complications of plasma cell dyscrasias.

Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal antibody. These disorders are associated with various systemic findings, including ophthalmological disorders. A search of PubMed, EMBASE, Scopus and Cochrane databases was performed in March 2021 to examine evidence pertaining to ocular complications in patients diagnosed with plasma cell dyscrasias. This review outlines the ocular complications associated with smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, plasmacytomas, multiple myeloma, Waldenström's macroglobulinemia, systemic amyloidosis, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome, and cryoglobulinemia. Although, the pathological mechanisms are not completely elucidated yet, wide-ranging ocular presentations have been identified over the years, evolving both the anterior and posterior segments of the eye. Moreover, the presenting symptoms also help in early diagnosis in asymptomatic patients. Therefore, it is imperative for the treating ophthalmologist and oncologist to maintain a high clinical suspicion for identifying the ophthalmological signs and diagnosing the underlying disease, preventing its progression through efficacious treatment strategies.

Lactoferrin and Activated Protein C: Potential Role in Prevention of Cancer Progression and Recurrence.

Existing therapeutic interventions for controlling cancer are limited and associated with side effects. Furthermore, the recurrence of cancer poses a significant challenge to the cure of cancer. Therefore, avenues are wanted to find novel therapies for cancer treatment and cancer recurrence. In this review, we have highlighted that lactoferrin (LF) and activated protein C (APC) carry enormous potential in cancer treatment. Studies have shown that the decreased level of APC and impaired function of APC are associated with cancer progression and cancer-related mortality. Moreover, APC plays an important role in preventing prothrombotic state-mediated cancer progression and deaths. LF can also inhibit the progression of cancer by controlling the generation of reactive oxygen species, triggering the apoptosis of cancer cells, arresting the cell cycle and hindering the angiogenesis process. Additionally, APC and LF could have the potential to inhibit neutrophil extracellular traps (NETs) formations which are involved in cancer progression and the reawakening of dormant cancer cells. Hence, in this review, the anticancer potential and mechanism of APC and LF along with their potential to mitigate inflammation and NETs-mediated cancer progression and recurrence has been discussed. Additionally, possible future strategies to develop effective and safe anticancer treatment using LF and APC have also been discussed in this review.

Targeting Apoptotic Pathway of Cancer Cells with Phytochemicals and Plant-Based Nanomaterials.

Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network.